Maintaining a Healthy Microbiome

Maintaining a Healthy Microbiome

1 Overview

Summary and Quick Facts

  • Most people are familiar with the importance of the microbiome for gut health but may not know that the microbiome can affect everything from mood to heart health.
  • This protocol will teach you about the wide-ranging influence of the microbiome and what you can do to keep it healthy.
  • Supplementation with probiotics and eating a diet that emphasizes unprocessed plant-based foods can go a long way toward improving the health of the microbiome and overall health.

What is the Microbiome?

The microbiome is the community, environment, and genetic material of microbes that live in the human body. There are estimated to be at least the same number of microbial cells in the body as human cells. People often associate the microbiome with gut health; however, research has demonstrated the microbiome’s role in many areas of human health.

Exploration of the microbiome has yielded startling discoveries: the microbes in our bodies are involved in gut, brain, oral, heart, and immune health, to name just a few. We are only recently discovering the implications of the microbiome on overall health.

Natural interventions such as probiotics and improved diet may help balance the microbiome and improve many aspects of health.

What Factors Contribute to Microbiome Development and Disturbances?

  • Vaginal birth versus C-section
  • Antibiotic use
  • Dietary patterns
  • Hormonal cycles, and more

What Health Effects are Associated with an Imbalanced Microbiome?

A shift in the microbiome, such as one that lowers beneficial species and/or boosts potentially harmful species, is known as dysbiosis. Dysbiosis of the gut has been linked with many chronic diseases and conditions, including:

  • Allergies
  • Cancer
  • Obesity
  • Depression
  • Leaky gut and chronic inflammation
  • Small intestinal bacterial overgrowth (SIBO)
  • Cardiovascular disease, and more

What Dietary and Lifestyle Changes Can Be Beneficial for the Microbiome?

  • Include more fiber (whole grains, legumes, fruits and vegetables) and less animal proteins and saturated fats in your diet
  • Add omega-3 fatty acids and fermented foods such as yogurt, soy sauce, and miso to your diet
  • Avoid excess alcohol
  • Get plenty of sleep and try to manage stress efficiently
  • Exercise regularly

What are Emerging Therapies for Microbiome Health?

  • Fecal microbiota transplantation
  • Phage therapy (viruses to attack harmful bacteria while leaving helpful bacteria and human cells untouched)

What are Probiotics?

Probiotics are living microorganisms, such as bacteria, that can promote health when they are ingested. Commonly used bacterial species are from the Lactobacillus and Bifidobacterium genera. Probiotics are generally safe; however, anyone who is very old, very young, or immunocompromised (eg, cancer patients, patients on immunosuppressive drugs, etc.) should consult a doctor before trying a probiotic.

Which Probiotics May be Helpful for Health?

  • Digestive health. L. reuteri, Saccharomyces boulardii, and L. rhamnosus may decrease the duration or prevent the onset of diarrhea. Other strains can be effective for relieving bloating, irritable bowel syndrome, reflux, and more.
  • Cardiovascular health. L. casei and L. plantarum may help improve or prevent the onset of hypertension. L. acidophilus, L. reuteri, and L. plantarum may help reduce cholesterol levels.
  • Oral health. L. reuteri may reduce plaque formation and improve oral health in people with periodontal disease. Other strains can improve oral health and reduce the occurrence of cavities as well.
  • Skin health. Early clinical research has shown that L. acidophilus and B. bifidum may help reduce acne. A mix of strains from the Lactobacillus and Bifidobacterium species may help improve or reduce the risk of eczema.
  • Vaginal and urinary health. Lactobacillus probiotic combinations have been effective in preventing and treating vaginal dysbiosis, and recent findings indicate long-term Lactobacillus supplementation may help clear HPV infection as well.
  • Respiratory and immune health. A specialized dried yeast fermentate from S. cerevisiae was shown to reduce seasonal allergies, and L. rhamnosus as well as other probiotic strains may reduce the occurrence of upper respiratory tract infections.
  • Mental health. L. helveticus in combination with B. longum were shown to improve mood and wellbeing.

2 Introduction

The human body exists in a dynamic and interdependent relationship with microbes. The skin, digestive tract, airways, vagina, eyes, and ears each have unique microbial ecosystems (Sender 2016; Proctor 2017; Thursby 2017; Huang 2011; Martin 2012; Dibb 1990; Lu, Liu 2016). There is even evidence that regions of the body long thought to be sterile, such as the placenta, urinary tract, uterus, lungs, blood, and even the brain, can harbor communities of microbes (Falana 2015; Potgieter 2015; Branton 2013; Whiteside 2015; O'Dwyer 2016; Chen 2017; Thomas-White 2016). In healthy humans, these complex ecosystems include a range of microorganisms, from bacteria and viruses to fungi and eukaryotes (Lloyd-Price 2016). Rather than being viewed solely as a reservoir for infection, these communities of microorganisms are now recognized as essential to our health as individuals and as a species (Davenport 2017; Turnbaugh 2007).

Historically, the term microbiome has been used to refer to the genetic material of the microbes, while microbiota refers to a community of microbial species (Knight 2017; D'Argenio 2015). These terms have come to be used interchangeably. In this protocol, microbiome will be used to refer to both groups of microorganisms and to their combined genetic material.

The number of microbial cells we harbor is estimated to be at least equivalent to the number of human cells in the body (Sender 2016; Knight 2017). The gut microbiome, which is the largest subset of the human microbiome, includes over 1,000 different bacterial species (across individuals) (Koboziev 2014; Lloyd-Price 2016) and accounts for about 2‒4 pounds of body weight per person (D'Argenio 2015). Furthermore, about 5 million microbial genes have been found in the gut, which is vastly more than the approximately 22,000 protein-encoding genes in the entire human genome (Ursell 2012; D'Argenio 2015). Only recently have we begun to understand and appreciate the significance of our evolutionary relationship with our microbial ecosystems (Davenport 2017).

This protocol describes the microbiome as a whole and its regional subsets. It presents a brief summary of what scientists know about how the microbiome interacts with our own cells and influences our health. This protocol also summarizes how the microbiome is shaped and maintained, and presents dietary and lifestyle strategies for supporting healthy microbial communities, as well as novel and emerging technologies for manipulating the microbiome: fecal microbiota transplant and phage therapy. Finally, this protocol details current and emerging research about the use of probiotics—living beneficial microorganisms—to prevent and treat disease.

3 Background

Microbiome Research

The Human Microbiome Project (HMP) was launched in 2008 by the National Institutes of Health (NIH) as an extension of the Human Genome Project (Turnbaugh 2007; Huse 2012; Peterson 2009). It is an ongoing worldwide undertaking that seeks to understand microbial communities and their variations in and on healthy humans (Turnbaugh 2007), beginning with five major body regions: the gastrointestinal tract, skin, vagina, respiratory tract, and oral cavity (Gevers 2012). A major goal of the HMP is to create a resource for determining how altered microbial patterns may contribute to disease and how to restore healthy microbial balance (Ursell 2012; Gevers 2012; Foxman 2010). Thanks to advances in gene sequencing technologies, knowledge about the microbiome is expanding rapidly (Knight 2017).

The human microbiome is extremely diverse and surprisingly variable: while only approximately 0.5% of the human genome is variable between individuals, the microbiome can vary dramatically between individuals (Ursell 2012; Mayor 2007). Much of this variability is due to differences in diet, environment, genetics, antibiotic use, and microbial exposure early in life (Human Microbiome Project Consortium 2012; Lloyd-Price 2016; Wischmeyer 2016). The diversity and variability of the human microbiome makes its characterization extremely challenging (Ursell 2012; Lloyd-Price 2016; Johnson 2016; Lozupone 2012).

Beneficial Microbes

The largest and most heavily studied component of the human microbiome resides in the gut. Microbiome researchers have estimated that each person is host to about 160 distinct intestinal bacterial species (Lloyd-Price 2016). Lactobacillus and Bifidobacterium species, encountered during birth and present in breastmilk, are among the earliest colonizers of the infant gut, and they shape subsequent colonization with other species (Koboziev 2014). While Lactobacillus and Bifidobacterium species become less abundant in the intestinal microbiome of adults as compared with infants (Arboleya 2016; Sghir 2000), they have been the focus of much attention due to their beneficial health effects, modulation by diet and environment, and possible therapeutic effects when used as probiotic supplements (Evivie 2017; O'Callaghan 2016; Derrien 2015; Rodriguez 2015).

Functions of a Healthy Microbiome

Digestion

Microbes in the intestines produce enzymes that can break down certain food components that human digestive mechanisms alone cannot (Thursby 2017; Kau 2011). A healthy microbiome therefore allows us to tolerate otherwise indigestible plant foods and extract otherwise inaccessible nutrients from them (Turnbaugh 2007; Krajmalnik-Brown 2012).

Microbial enzymes are especially important for breaking down indigestible and partially digestible carbohydrates, including certain starches and fibers. This enhances the body’s ability to extract and absorb monosaccharides (single-unit sugars) that can be turned into energy (Flint 2012; Krajmalnik-Brown 2012). Gut bacteria metabolize and activate many plant polyphenols and other phytochemicals, which may have important implications for health (Ozdal 2016; Tomas-Barberan 2016; Theilmann 2017; Swanson 2015). For example, certain intestinal bacteria transform lignans and isoflavones into active compounds linked to improved female hormone signaling (Gaya 2016).

The gut microbiome is also equipped with enzymes to digest dietary proteins. Some microbes are more efficient protein-digesters than others. Some of the byproducts of microbial protein digestion can have toxic effects that may contribute to negative health outcomes. A Western-style diet, which is high in animal protein and low in indigestible fibers, has a considerable detrimental impact on gut microbiome composition by supporting species that can best adapt to a high-protein environment (Montemurno 2014; Graf 2015; David 2014).

Microbial Byproducts

A major metabolic pathway used by intestinal microbes to produce energy is fermentation, which is a metabolic process that does not require oxygen (Thursby 2017; Monda 2017). The main byproducts of microbial fermentation, primarily of dietary fibers, are short-chain fatty acids, including butyrate, acetate, and propionate. Short-chain fatty acids are not only a major energy source for cells lining the large intestine, but also regulate immune activity, prevent infections, reduce inflammation, enhance the absorption of minerals such as calcium, have anti-cancer properties, and can influence cholesterol levels, appetite, and weight gain (Sharon 2014; Flint 2012; Krajmalnik-Brown 2012; Whisner 2017).

Byproducts of protein fermentation are somewhat different than those of carbohydrate fermentation and include a number of compounds that are potentially toxic. Some of these toxic byproducts are believed to contribute to health problems associated with diets high in animal protein, such as colon cancer and some chronic diseases (Montemurno 2014).

Bile acids are the main components of bile, which is secreted from the gallbladder into the small intestine during digestion (Taoka 2016). Microbial enzymes transform bile acids into a wide array of byproducts, some of which are reabsorbed (Ryan 2017). In addition to assisting in the digestion and assimilation of fats and fatty compounds, reabsorbed bile acids and their byproducts help regulate lipid and glucose metabolism and energy production (Taoka 2016; Ryan 2017). How bile acids modulate cardio-metabolic conditions such as obesity, diabetes, fatty liver, and heart disease is still being explored (Ryan 2017; Chiang 2017).

Interestingly, bile acids also contribute to shaping the gut microbiome via antimicrobial effects and interactions with the immune system (Ramirez-Perez 2017; Chiang 2017; Ridlon 2014; Nie 2015). Bile acids may be one of the ways to connect diet, which influences the types of bile acids produced, to the composition of the gut microbial populations, which may be supported or suppressed by the presence of certain bile acids (Ridlon 2014; Islam 2011; Wahlstrom 2016).

Other byproducts of microbial activity that benefit human hosts include B vitamins, vitamin K, and amino acids such as tryptophan (Jandhyala 2015; Etienne-Mesmin 2017; Conly 1992; Morowitz 2011; Paiva 1998). Several tryptophan-derived compounds have important impacts on the functions of the immune and nervous systems (Cervenka 2017; Jenkins 2016). For example, approximately 90% of the body’s serotonin is made in the gastrointestinal tract from tryptophan (Sharon 2014; Kato 2013; Mawe 2013). Bacteria that colonize the intestines may also produce other neurotransmitters, such as acetylcholine, norepinephrine, dopamine, and gamma-aminobutyric acid (GABA) (Clark 2016; Galland 2014). These neurotransmitters exert a host of peripheral effects, such as modulation of the stress response, which ultimately influences brain function and mood (Galland 2014; Jenkins 2016; Robson 2017).

Gut microbes play an important role in metabolizing some medications, in some cases activating them prior to absorption (Noh 2017). Some of these medications, such as the anti-diabetes drug metformin, appear to rely at least in part on altering the gut microbiome to achieve their therapeutic effect (Wu 2017; Rena 2017). In one case report, targeting the growth of beneficial microbes with a food-based supplement improved both metformin’s tolerability and efficacy (Greenway 2014). Based on this intriguing case report, researchers carried out a small clinical study on 10 diabetic individuals. They found supplementation with the microbiome-targeted nutrients agave inulin, oat beta-glucan, and blueberry polyphenols improved metformin’s tolerability and efficacy (Burton 2015). Gut microbes also help process and detoxify harmful environmental compounds such as carcinogens (Turnbaugh 2007; Moon 2016).

Infection Control

A critical function of the microbiome is preventing the overgrowth of harmful microbes. Some mechanisms by which it achieves this are: maintaining an acidic pH; secreting antimicrobial substances; inhibiting microbial toxicity; competing for nutrients and resources; preventing harmful organisms from adhering to superficial cells; and activating local immune cells (Tosh 2012; Surendran Nair 2017; Knaus 2017).

Immune Regulation

The microbiome plays an integral role in immune regulation (Gulden 2017). Almost all tissues and organs, whether in direct contact with or further away from the microbiota, are influenced by the microbiota. Microbes and their products communicate with the immune system, promote its development and maturation, and guide immune responsiveness (Brown 2017; Shi 2017; Correa-Oliveira 2016; Shibata 2017; Belkaid 2014).

The immune regulatory role of the microbiome also helps prevent the dysfunctional immune activity that can lead to allergies, autoimmune diseases, and chronic inflammatory conditions (Brown 2017; Fujimura 2015). Microbiome disturbances have been linked to chronic inflammatory conditions such as periodontal disease, bacterial vaginosis, atopic dermatitis, inflammatory bowel disease, rheumatoid arthritis, and obesity (Correa-Oliveira 2016; Yamazaki 2017). Furthermore, interactions between the gut microbiome and immune system are important for stimulating the renewal and repair of cells lining the gut epithelium where the gut microbiome resides (Turnbaugh 2007).

Metabolism

The microbiome, particularly in the gut, appears to play a substantial role in regulating metabolism. From the very beginning of life, factors that shape the microbiome have been shown to be indicators of the risk of obesity or metabolic diseases. For example, Cesarean section (C-section) birth, a formula-based diet, illness, and antibiotic use early in life have all been correlated with higher rates of childhood overweight and obesity (Rosenbaum 2015; Mueller 2015; Korpela 2016; Li 2017). Maternal antibiotic use during pregnancy or breastfeeding has also been shown to impact the infant microbiome and has been correlated with childhood obesity risk (Cassidy-Bushrow 2017; Lemas 2016; Mor 2015).

Patterns of gut microbial imbalance have been seen in adults with metabolic diseases such as obesity, non-alcoholic fatty liver disease, and type 2 diabetes (Sedighi 2017; He 2017; Lippert 2017; Ma 2017). Certain dietary changes, such as consuming more fiber or capsaicin from chili peppers, calorie restriction, and weight loss, have been associated with beneficial changes in the gut microbiome, which may contribute to improvements in metabolic disturbances. Diets high in fat, protein, and sugar, on the other hand, can disrupt microbiome health (Vinke 2017; Rosenbaum 2015; Yang 2017; Ley 2006; Kang, Wang 2017; Singh 2017; Kang 2016; Turnbaugh 2009).

Circadian Rhythms

The intestinal microbiome undergoes daily shifts in composition that are driven in part by dietary patterns. In an animal model, interruptions in circadian rhythms intended to mimic jet lag or night-shift work altered the normal cycling of the microbiome, leading to metabolic disturbances (Thaiss 2014; Zarrinpar 2016). Emerging evidence further indicates that the relationship between circadian rhythms and the microbiome may be bidirectional, so that imbalances in the microbiome can disrupt circadian signaling, resulting in a cycle of disordered daily biological rhythms and metabolic perturbations (Thaiss 2014; Leone 2015; Wang, Kuang 2017).

4 Establishing and Shaping the Microbiome

The infant microbiome plays a foundational role in educating the immune system and is therefore an important determinant of lifelong health (Dominguez-Bello 2016). Its composition is shaped by multiple factors, including mode of birth, human genetic factors, geography and culture, diet and lifestyle, physiology, illnesses, surroundings, and contact with other people and pets (van der Meulen 2016; Turnbaugh 2007; Song 2013; Goodrich 2014; Yatsunenko 2012; Tasnim 2017). In addition, the use of medications such as antibiotics and proton pump inhibitors can influence the microbiome (van der Meulen 2016).

Our first exposure to the microbiome is at birth (Falana 2015; Koboziev 2014). During vaginal delivery, the newborn becomes colonized with microorganisms that originate from the maternal birth canal and skin (Knight 2017; Krajmalnik-Brown 2012; Koboziev 2014). Compared with babies born vaginally, the microbiomes of those born by C-section have been found to have more microbes that originate from the mother's skin and fewer microbes that originate from the vaginal canal (Krajmalnik-Brown 2012; Dominguez-Bello 2016; Rutayisire 2016). Bifidobacterium bacteria, as well as Lactobacillus species, are especially important early colonizers of the infant gut, where they help guide the development of a healthy microbiome and the maturation of the immune system (Koboziev 2014; Mueller 2015).

The mother's vaginal microbiome is critical in establishing the initial gut microbiome in the newborn during birth, and it helps shape immune system maturation and metabolism. This microbiome transmission from the mother to the newborn occurs during a critical period of the newborn brain development. Environmental factors, such as maternal stress during pregnancy, can change the vaginal microbiome and its transmission to the infant, and may affect neurological development of the infant later in life (Jasarevic, Rodgers 2015; Jasarevic, Howerton 2015; Jasarevic 2017).

Breastfeeding is another opportunity for the transfer of Lactobacillus and Bifidobacterium species, as well as other bacterial species, to the infant (Soto 2014; Mueller 2015; Urbaniak 2012). In addition, certain prebiotic carbohydrates found in human breast milk (called human milk oligosaccharides) support the growth of Bifidobacterium species, which are important in the infant's gut, where they promote the healthy development and function of the intestinal mucosal surface and the immune system (Knight 2017; Mueller 2015).

Human Milk Oligosaccharides
Breast milk provides all of the nutrients required for a newborn's healthy growth and development. It also contains an array of biologically active compounds that protect and support the newborn during early immune, cognitive, and metabolic development (Martin 2016; Kulinich 2016; Castanys-Munoz 2016). These are well known to include maternal immune components such as antibodies, immune cells, and cytokines—chemicals needed for immune signaling (Witkowska-Zimny 2017; Cabinian 2016). Only recently has the importance of specialized breast milk oligosaccharides in establishing a healthy gut microbiome and balanced immune function been appreciated (Kulinich 2016; Donovan 2016).

Human milk oligosaccharides are a complex mixture of small indigestible carbohydrates that promote the growth of beneficial gut bacteria. In particular, Bifidobacterium species, abundant in the intestines of healthy breastfed infants, are able to ferment these oligosaccharides (Donovan 2016; O'Callaghan 2016). By supporting the presence of beneficial bacteria, human milk oligosaccharides enhance the establishment of normal intestinal barrier function and mucosal immunity. Findings from laboratory and animal studies also suggest human milk oligosaccharides may directly impact mucosal and immune maturation and function, and exert direct antimicrobial actions against infection-causing microorganisms (Donovan 2016; Ackerman 2017).

The differences in microbiome composition between babies born vaginally versus by C-section may explain the increased risks of allergies and asthma, obesity, type 1 diabetes, and neurodevelopmental disorders associated with C-section birth (Ho 2015; Moya-Perez 2017). Introducing C-section-born infants to vaginal microbes by swabbing them with maternal vaginal fluids at birth is a new strategy being explored to help establish a healthy microbiome (Dominguez-Bello 2016). Formula feeding also disrupts the healthy infant microbiome and has been associated with an increased risk for immunologic and metabolic disorders later in life. Even small amounts of supplemental formula can alter the gut microbial populations (Mueller 2015).

The infant gut microbiome undergoes changes in the first two to four years of life and then becomes more similar to the one found in adults (Chan 2013). Changes in diet and the body contribute to this shift in the microbial profile. Exposure to animals, such as pets, during these younger years is associated with a lower risk of allergies. Microbial patterns can also be altered by antibiotic use, microbes in the surroundings, and illness (Xu 2015; Francino 2015; Ojima 2016).

After this time of rapid diversification and expansion, the microbiome becomes relatively stable, and changes are more gradual (Knight 2017; Krajmalnik-Brown 2012). The relationship between aging and the microbiome is still being explored, but evidence suggests gut microbial profiles of the elderly are different from those of younger adults and are correlated with measures of frailty, poor diet, and health problems (Claesson 2011; Claesson 2012).

While a healthy microbiome is generally resistant to changes in its environment, and returns to the previous state afterwards (Lloyd-Price 2016), it is nonetheless susceptible to certain disrupting factors. Antibiotics, for example, can have dramatic effects on the microbiome, and the ability to recover to the pre-antibiotic microbial balance differs between individuals. Changes in eating habits can also cause profound and rapid alteration in the microbiome that can be brief or persistent. Hormonal cycles, travel, illness, and aging are other examples of factors that shape the microbiome (Krajmalnik-Brown 2012; D'Argenio 2015; Xu 2015; Zapata 2015).

5 Dysbiosis

A shift in the microbial balance away from a pattern associated with health is known as dysbiosis (Wischmeyer 2016; Lloyd-Price 2016; Chan 2013). A healthy microbiome is highly diverse and characteristically resilient to physiological stress; on the other hand, a dysbiotic microbiome is generally marked by smaller numbers of beneficial species, the presence of more species with disease-causing potential, and lower species diversity (Chan 2013).

Dysbiosis in the gut increases the risk of immune perturbations both inside and outside of the digestive tract (Brown 2017). In addition, gut dysbiosis has been associated with a growing list of chronic diseases and conditions that includes—but is not limited to—the following (Lloyd-Price 2016; Wang, Du 2017; Morris 2016; Potgieter 2015; Knight 2017; Strati 2017; Marasco 2016; Chen 2018; Distrutti 2016; Flowers 2015):

  • allergies
  • asthma
  • autism
  • autism spectrum disorders
  • autoimmune diseases
  • cancer
  • cardiovascular disease
  • celiac disease
  • chronic fatigue syndrome
  • depression
  • type 1 and type 2 diabetes
  • inflammatory bowel disease
  • irritable bowel syndrome
  • multiple sclerosis
  • neurological diseases
  • obesity
  • osteoporosis
  • cognitive and emotional health

Dysbiosis, Leaky Gut, and Systemic Inflammation

Imbalanced intestinal microflora can trigger chronic mucosal inflammation, which increases intestinal permeability and creates a condition known as leaky gut (van der Meulen 2016; Morris 2016; Nagpal 2017). Intestinal permeability is controlled by interactions between proteins on the surfaces of adjacent cells lining the intestinal wall, which form structures known as tight junctions. Zonulin is a protein that modulates these tight junctions, and increased zonulin levels in the circulation are considered to indicate an impaired intestinal barrier (Ohlsson 2017; Fasano 2012; Moreno-Navarrete 2012).

A leaky gut allows the absorption of small food components and bacteria, which can then trigger systemic immune activation and inflammation (van der Meulen 2016). Gut microbes and microbial products and toxins can also cross a leaky gut (Slyepchenko 2017; van der Meulen 2016). This can lead to immune and inflammatory activation in distant tissues and organs, and is thought to be an important mechanism in the development of autoimmune diseases and diseases related to systemic inflammation (Morris 2016; Slyepchenko 2017; Nagpal 2017; van der Meulen 2016).

Small Intestinal Bowel Overgrowth

While the colon (part of the large intestine) has a complex and diverse microbial community, comprising more than 70% of gut microbes (Ghoshal 2017), the healthy small intestine has a more limited microbiome (Ponziani 2016). Small intestinal bacterial overgrowth (SIBO) is a pattern of dysbiosis that is increasingly recognized as a cause of common digestive symptoms such as indigestion, bloating, flatulence, and disordered bowel function, and as a possible underlying feature of irritable bowel syndrome (Ghoshal 2017; Thompson 2016; Sachdev 2013). The most commonly studied antibiotic treatment for patients with SIBO is rifaximin (Xifaxan), a non-absorbable antibiotic. In addition, preliminary evidence suggests probiotic therapy, alone or in combination with rifaximin, may be helpful. Promising results have been reported from trials using probiotics containing Saccharomyces boulardii, or rifaximin together with Lactobacillus casei (Ghoshal 2017; Chedid 2014).

6 Diet and Lifestyle Strategies for Supporting a Healthy Microbiome

The fundamental link between the gut microbiome, diet, and physiology has become increasingly apparent (Amato 2015), and underscores the power of diet as a means to maintain a healthy microbiome—and thus a healthy body. The gut microbiota is in constant evolution, varies greatly among individuals, and modulates metabolism, opening the possibility to predict individual responses to particular foods as part of personalized medicine interventions (Xu 2015; Vanamala 2015; Davenport 2017).

Western versus High-Fiber Diet

A high-fat diet, especially one including large amounts of saturated fatty acids, has been shown to induce gut dysbiosis, intestinal permeability, and inflammation (Araujo 2017; Yang 2017; Silva Figueiredo 2017). A diet high in complex carbohydrates and fiber, on the other hand, supports the growth of microbial populations that are efficient carbohydrate fermenters. These bacteria produce short-chain fatty acids and other fermentation products that support the health of the intestinal lining and have positive effects on immune and metabolic functions (Montemurno 2014; Yang 2017).

A Western-type diet in particular—high in animal proteins and fat and low in fiber—selects for bacteria that metabolize proteins efficiently and those that can best tolerate bile acids secreted in response to high-fat meals. Microbial metabolism of proteins and certain bile acids creates byproducts that appear to contribute to the development of diseases known to be closely connected to a Western diet, including colon cancer, cardiovascular disease, and metabolic disorders (Montemurno 2014; Ridlon 2014). Conversely, in one study, a Mediterranean-style diet with 35% of calories from fat, and a low-fat diet (<30% total fat), each improved gut microbial communities in subjects with obesity and metabolic dysfunction after two years (Haro 2017).

Prebiotics are carbohydrates that are completely or partially indigestible and that promote the growth of beneficial bacterial populations. These include small carbohydrates called pectin-oligosaccharides, large and small fructose-based carbohydrates known as inulins, and resistant starch (Ferrario 2017; Kelly 2008). Legumes, fruits and vegetables, nuts, and whole grains are especially high in prebiotic fibers (Vinke 2017; Dahl 2015; Slavin 2013; Lamuel-Raventos 2017). These foods have long been recognized as the cornerstones of a healthy, high-fiber diet, including the Mediterranean diet, known to show benefits regarding a number of metabolic and inflammatory health problems (Fabbiano 2017; Montemurno 2014).

Omega-3 Polyunsaturated Fatty Acids

Although high-fat diets are generally associated with negative changes in the gut microbiome, different types of fats may have different effects. For example, omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to improve the microbial balance and increase anti-inflammatory immune activity in the gut and throughout the body (Watson 2017; Costantini 2017; Silva Figueiredo 2017). This may be due to increased positive interactions between the immune system and gut microbes, resulting in higher microbial diversity, increased short-chain fatty acid production, and improved intestinal barrier function (Candido 2017; Menni 2017; Costantini 2017).

Fermented Foods

Fermentation, mainly by lactic acid bacteria, has been used to preserve food and enhance flavor for thousands of years, and fermented foods are recognized for their probiotic and health-promoting nature (Hill 2017). Fermented foods are a source of vitamins, minerals, enzymes, and a range of biologically active, health-promoting peptides produced by microbes during fermentation. Fermented food consumption has been associated with health benefits such as improvements in: high blood pressure, high cholesterol levels, insulin resistance, certain digestive disorders, cognitive function, and immune function, and may lower risks of cardiovascular disease, diabetes, osteoporosis, and certain cancers (Tamang, Shin 2016). In addition, the living microbes present in fermented foods may act as probiotics when ingested (Sanlier 2017; Stanton 2005; Tamang, Shin 2016).

Table 1. Examples of microorganisms commonly used in food fermentation

Fermentation Microorganisms

Foods in Which They Are Typically Used

 Bacteria:

 

Acetobacter species

A. aceti subspecies aceti
A. pasteurianus
A. peroxydans
A. syzygii
A. okinawensis
A. malorum
A. tropicalis
A. pomorum

Used in fruit fermentation and are important in making many vinegars. They produce acetic acid, and are also present in kombucha, cocoa, and some wines.

Streptococcus species

S. thermophilus
S. faecalis
S. bovis

Widely used in dairy fermentation to produce such foods as yogurt and cheeses. They produce lactic acid and are also found in some vegetable ferments.

Lactobacillus species

L. delbrueckii
L. plantarum
L. lactis
L. acidophilus
L. brevis
L. fermentum
L. buchneri
L. nagelii

Widely used in dairy, vegetable, fruit, grain, and meat fermentations to produce cheeses, kefir, yogurt, cocoa, wine, sourdough, sausages, cucumbers, kimchi, olives, sauerkraut, kombucha, and many other foods.

Bifidobaterium species

B. longum
B. animalis subspecies lactis
B. breve

Added during dairy fermentation to boost probiotic content. They are found in some cheeses and yogurt.

Bacillus species

B. coagulans
B. subtilis

Used in soybean fermentation to produce natto and soybean pastes. B. subtilis is well known for producing the enzyme nattokinase.

Yeasts and Molds:

 

Saccharomyces species

S. cerevisiae
S. cerevisiae subspecies boulardii
S. uvarum

Used in grain fermentation to make beer, wine, and sourdough. They can also be found in kombucha, and some species are used as probiotics.

Aspergillus species

A. oryzae
A. sojae

Used to ferment soybeans and rice. A. oryzae (a.k.a. koji) in particular is important in the production of sake, miso, soy sauce, rice vinegar, and rice wine.

Rhizopus species

R. oligosporus
R. oryzae

Used to ferment soybeans and produce tempe and soy sauce.

Penicillium species

P. camemberti
P. roqueforti

Used to make white mold cheeses (eg, Camembert) and blue mold cheeses (eg, Roquefort)

Zygosaccharomyces species

Z. rouxii
Z. bailii

Used in soybean fermentation to produce miso and soy sauce. Also found in kombucha.

(Battcock 1998; Fernandez 2015; Tamang, Shin 2016; Tamang, Watanabe 2016; Pokusaeva 2011; Coton 2017; Mamlouk 2013; Suezawa 2008; Oliveira 2017; Laich 2002; Guenther 2011; Ropars 2017; Swain 2014; Londono-Hernandez 2017; Kitamoto 2015; Fijan 2014; Kawarai 2007; Kim 2017; Marongiu 2015; Gallone 2016; Krogerus 2017; Kelesidis 2012; Wang 2009; Mayo 2008; Lefeber 2011; Vogel 1993)

Alcohol (Ethanol)

Abuse and dependence on alcoholic beverages has been associated with dysbiosis leading to inflammation and increased permeability of the intestinal mucosa. Absorption of bacteria, microbial products, and other intestinal contents through the damaged mucosa may trigger inflammation in the liver and contribute to alcohol-related liver disease (Capurso 2017; Dubinkina 2017). Furthermore, some evidence suggests certain people with alcohol dependence may have increased gut permeability and higher scores for depression, anxiety, and cravings. Changes in microbiome composition found in this group of people pointed towards the possibility that the microbiome might be a potential target to reduce the risk of relapse in some people with alcohol dependence (Capurso 2017; Leclercq 2014).

Stress and Sleep

Stress and sleep disruption are closely connected and have been correlated with disturbances in the healthy balance of gut microbes (Weljie 2015; Galland 2014; Poroyko 2016; Benedict 2016). Dramatic reductions in gut microbial abundance and function have been noted following sudden acute stress events, such as a heart attack, trauma, or burn injury (Alverdy 2017). It is thought that high psychological stress conditions in the body trigger changes in the gut microbiome, which may lead to changes in the regulation of some neurotransmitters (Househam 2017). In addition, due to the bidirectional communication along the gut-brain axis, dysbiosis in turn can trigger dysfunctional activation of the stress response (Alverdy 2017; Bermon 2015; Rogers 2016; Clapp 2017).

Stress reduction may be one way to improve the health of the microbiome. Meditation has been shown to reduce activation of the stress pathways and suppress chronic inflammation, which may support beneficial gut microbial populations (Househam 2017). Furthermore, getting enough sleep and observing normal sleep/wake rhythms may both be important for supporting a healthy microbiome (Thaiss 2014; Parekh 2018; Anderson 2017).

More information is available in the Stress Management and Insomnia protocols.

The Gut-Brain Axis

The digestive tract has its own nervous tissue, called the enteric nervous system, that senses and responds to the gut environment and regulates gut activity. While the enteric nervous system can function independently, it also communicates closely with the body’s central nervous system through a network referred to as the gut-brain axis. The bidirectional nature of this communication explains not only how stress may affect digestion, but also how events in the digestive tract may influence the brain (Quigley 2018; Zhou 2015; Mayer 2014; Carabotti 2015). 

The gut microbiome is emerging as a key player influencing communication along the gut-brain axis. Gut microbes produce an array of neuroactive chemicals, help control intestinal barrier function, and modulate immune and inflammatory signaling, all of which influence signaling along nerve pathways (Carabotti 2015). Disturbances in the gut microbial community are now thought to be involved in neurological disorders such as Parkinson disease, Alzheimer disease, autism spectrum disorders, and in depression, anxiety, and chronic pain. Findings from animal research suggest that, most likely via the gut-brain axis, the intestinal microbiome may even shape appetite, feeding behavior, and taste preferences (Mayer 2015; Mayer 2014; Hu 2016). In a remarkable experiment, researchers transplanted fecal microbes from human Parkinson disease patients into genetically susceptible mice. This triggered manifestations of the disease, such as impaired movement, in the exposed mice, while the same genetically predisposed mice transplanted with fecal microbes from healthy people did not develop these symptoms (Sampson 2016).

Exercise

Regular moderate-intensity exercise is well known to mitigate stress, reduce chronic inflammation, and improve metabolism (Lalanza 2015; Beavers 2010; Nicklas 2009; McGarrah 2016; Sato 2003; Colombo 2013). Findings from several studies suggest physically active and highly fit individuals have greater gut microbial diversity with more beneficial microbes than sedentary people (Clarke 2014; Estaki 2016; Bressa 2017; Barton 2017; Petersen 2017). The observed benefits of exercise on immune response, metabolism, and overall health might be mediated in part by its beneficial effects on the gut microbiome (Bermon 2015; Monda 2017). In addition, some researchers have proposed that microbial byproducts may play a role in preserving skeletal muscle structure and function, particularly in the elderly, a cross-talk that is becoming known as the “gut-muscle axis” (Ticinesi 2017; Grosicki 2017).

7 Novel And Emerging Therapies For Microbiome Health

Fecal Microbiota Transplantation

One of the most exciting areas of microbiome research has been fecal microbiota transplantation, which involves the transfer of a fecal suspension, containing gut microbes, from a healthy subject to an unhealthy subject for therapeutic purposes. The procedure has generally been performed through enema or a tube that is introduced into the stomach or duodenum. However, in a 2017 study on patients with recurring Clostridium difficile infections, an oral capsule of freeze-dried fecal microbes was comparably effective to delivery via colonoscopy in preventing recurrences (Gallo 2016; Kao 2017).

Fecal microbiota transplantation has become an important treatment option in recurrent intractable C. difficile infections, for which its efficacy is close to 90% (Liubakka 2016; Cammarota 2017; Matijasic 2016). Clinical research, though in its early days, suggests it may also have value in treating a number of inflammatory and metabolic conditions associated with dysbiosis, such as inflammatory bowel disease (Matijasic 2016), irritable bowel syndrome (Distrutti 2016), obesity and type 2 diabetes (Marotz 2016), and autism spectrum disorders (Kang, Adams 2017). Furthermore, fecal microbiota transplantation so far appears to have an excellent safety profile (Cammarota 2017).

Phage Therapy

Bacteriophages, or phages, are viruses that infect specific bacteria but do not infect human cells (Doss 2017). Phages, believed to be the most abundant organisms on earth, are an integral part of the human microbiome, where they are thought to manage bacterial communities by limiting target species (Mirzaei 2017; Keen 2015). Phage therapy is being explored as an alternative to antibiotic therapy for certain conditions and, potentially, for eliminating harmful bacteria from the body's microbial communities (McCarville 2016; Lin, Koskella 2017).

An abundant and diverse community of phages inhabits the oral cavity, and specific phages or their enzymes have shown promise for treating periodontal disease and preventing dental plaque (Szafranski 2017). Phages that target infection-causing gastrointestinal bacteria such as Vibrio cholerae (the cause of cholera) (Yen 2017), Helicobacter pylori (Wan 2011), C. difficile (Nale 2016), Shigella dysenteriae (Mai 2015), and some harmful Escherichia coli strains (Dalmasso 2016) have been identified and hold therapeutic potential. Older reports of phage therapy being used successfully to prevent and treat various other types of bacterial infections, including those of the skin, urinary tract, and eyes, have emerged and provide a basis for future research (Chanishvili 2012).

8 Introduction to Probiotics

Probiotics are living microorganisms that promote health when ingested in sufficient amounts (Shi 2016). Most probiotic supplements contain bacteria, and commonly include species from the Lactobacillus and Bifidobacterium genera (Ciorba 2012; Islam 2016; Saini 2010). Several species of fungal Saccharomyces are also used in probiotic supplements (Fakruddin 2017). Probiotic supplements are usually measured in colony forming units (CFUs), which represent the number of viable cells (Weese 2011; Wallace 2017).

Microorganisms are classified in a hierarchy of families, genera, species, and strains. The genus is indicated by an organism's first name; the species is its second name, and is followed in some cases by the strain designation (Khalighi 2016). For example, Lactobacillus acidophilus La-14 is a well-described probiotic (Stahl 2013) of the genus Lactobacillus, species acidophilus, and strain La-14 (Salvetti 2012).

A growing body of probiotic research is establishing the safety and therapeutic efficacy of many individual strains (Sanders 2010; Shi 2016).

Probiotics: Safety Considerations

Probiotics have a good safety record for human use for a variety of conditions. However, some potential areas of concern include the very young or very old, people with compromised immunity due to cancer, people who are taking potent immunosuppressive drugs after having received an organ transplant or those who are critically ill in intensive care (Happel 2018). A research study reported that most adverse effects were observed in frail elderly and terminally ill people, while in HIV-infected individuals the benefits of probiotics outweigh their risks (Happel 2018; Stadlbauer 2015).

One case report noted that fungemia with Saccharomyces boulardii developed in two newborns, of which only one was treated with the probiotic, and the second one contracted the infection from the first infant, who was located in the adjacent cot (Perapoch 2000). Fungemia with S. boulardii was also reported in an 8-month old infant with acute myeloid leukemia who was receiving probiotics to prevent chemotherapy-associated diarrhea (Cesaro 2000).

Fungemia with S. boulardii was reported in an elderly patient with Clostridium difficile colitis who was treated with vancomycin (Cherifi 2004), and in several patients in intensive care units treated with antibiotics who had central venous catheters (Lherm 2002). Bacteremia with L. acidophilus was seen in a patient with AIDS and Hodgkin disease (Ledoux 2006), and bacteremia with L. rhamnosus GG was reported in a 17-year-old boy with ulcerative colitis who was treated with systemic corticosteroids and infliximab (Remicade) (Vahabnezhad 2013).

Other populations potentially at risk from probiotic-related complications, according to the Food and Drug Administration, include people with artificial heart valves, and those with an active bowel leak or active intestinal disease such as colitis, due to the possibility that the probiotics would cross the gut wall (Doron 2015).

A systematic review and meta-analysis found that probiotics during pregnancy do not increase the risk of preterm birth and do not result in any adverse outcomes in the mother or the infant (Jarde 2018).

Consultation with a qualified healthcare provider is advised before probiotic use for people in the risk groups described here.

9 Probiotics For Digestive Health

Probiotic therapy has been shown to be safe and effective in the prevention and treatment of a wide range of digestive ailments and is likely to become increasingly important as challenges related to antibiotic resistance grow (Pamer 2016; Wilkins 2017). Probiotics likely preserve digestive health through their anti-microbial, anti-inflammatory, and immune-modulating actions on the intestinal lining (Surendran Nair 2017; Wilkins 2017). In a randomized, double-blind, placebo-controlled clinical trial on elderly volunteers, a probiotic combination that contained Bifidobacterium bifidum BB-02, B. lactis BL-01, and oligofructose, led to beneficial changes on size and diversity of the gut bacterial populations, which are often affected during aging (Bartosch 2005).

Diarrhea

A systematic review and meta-analysis of clinical trials reported that Lactobacillus reuteri DSM 17938, at doses of 100–400 million CFUs per day for five to seven days, decreased the duration of diarrhea in children (Urbanska 2016). In another systematic review and meta-analysis, L. rhamnosus GG, in doses between 400 million and 120 billion CFUs per day, effectively prevented antibiotic-associated diarrhea in children and adults (Szajewska 2015b).

Traveler's diarrhea is a common form of acute infectious diarrhea that is estimated to affect 25% of travelers in their first two weeks abroad (Giddings 2016). Although trials have shown mixed results, supplements containing the probiotic yeast Saccharomyces boulardii (5‒10 billion CFUs per day) have demonstrated promising effects in preventing traveler's diarrhea (Giddings 2016; Ouwehand 2017). Other helpful probiotics include L. rhamnosus GG, L. acidophilus, and B. bifidum (Giddings 2016).

Antibiotic-associated Diarrhea

Several probiotic supplements have shown promise in preventing antibiotic-associated diarrhea. S. boulardii in particular was found to reduce the risk of antibiotic-associated diarrhea by 53% in a systematic review and meta-analysis of 21 randomized controlled trials with a total of 4,780 antibiotic-treated participants (Szajewska 2015b). In another systematic review and meta-analysis of 12 randomized controlled clinical trials with a total of 1,499 antibiotic-treated participants, L. rhamnosus GG reduced treatment-related diarrhea risk by 51% (Szajewska 2015a). The most recent systematic review and meta-analysis, with 17 randomized controlled trials and a combined total of 3,631 non-hospitalized antibiotic-treated patients, found that those receiving any probiotics were 51% less likely to develop antibiotic-associated diarrhea. In this analysis, supplements containing L. rhamnosus GG and S. boulardii in daily doses higher that 5 billion CFUs appeared to be more protective (Blaabjerg 2017).

Clostridium difficile Diarrhea

C. difficile is a spore-forming bacterium that can cause inflammation of the large intestine (colitis) and diarrhea in vulnerable individuals (Heinlen 2010). It is the most common cause of diarrhea acquired in hospitals (Ofosu 2016). The main risk factors for C. difficile infection include hospitalization or institutionalization, antibiotic use, gastrointestinal surgery or procedures, serious illness, compromised immune function, and older age. Proton pump inhibitors, a class of medications used to treat gastroesophageal reflux, gastritis, and peptic ulcer disease, also increase risk (CDC 2012; Khanna 2012). The incidence and severity of C. difficile infections is rising, with hospitalizations for the infection in the United States doubling between 2000 and 2010 (Lessa 2015; Lessa 2012). Antibiotics are the standard medical treatments for C. difficile diarrhea, and recurrence is common (Al-Jashaami 2016). 

Probiotic supplements have been shown to be safe and effective in preventing C. difficile-associated diarrhea. One community hospital affected by a major outbreak of C. difficile infections reported a 73% reduction in cases and a 39% reduction in recurrences after implementing a policy of giving a probiotic supplement to all patients within 12 hours of beginning any antibiotic regime. The probiotic provided 50 billion CFUs per day of a combination of L. acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. By continuing to include probiotic therapy in their prevention strategy, the hospital was able to maintain very low occurrence and recurrence rates of C. difficile infections for the 10 years preceding the publication of their report (Maziade 2015).

In a 2017 randomized controlled trial, a four-strain probiotic containing L. acidophilus NCFM, L. paracasei Lpc-37, B. lactis BI-04, and B. lactis Bi-07 was compared with placebo as an add-on to standard medical therapy in 33 participants with their first diagnosis of mild-to-moderate C. difficile infection. After 28 days, the duration of diarrhea was found to be shorter in those treated with the probiotic combination (Barker 2017).

A 2017 systematic review and meta-analysis that included data from 19 studies, with a combined total of 6,261 hospitalized adults receiving antibiotics, found that starting probiotic therapy within the first two days of antibiotic treatment led to a 68% reduction in C. difficile infection risk, and efficacy was diminished with every day of delay in starting the probiotic therapy (Shen 2017). Other meta-analyses have drawn similar conclusions: probiotic supplements reduced antibiotic-associated C. difficile diarrhea risk by approximately 60% in adults and children, both within and outside of hospital settings, with a high degree of safety. Hospitalized patients were more likely to benefit. While most trials used supplements with one or more Lactobacillus species, Lactobacillus plus Bifidobacterium species, or Saccharomyces species, the preventive effect did not appear to be species-specific (Goldenberg 2017; Lau, Chamberlain 2016).

Constipation

The gut microbiome is one of the important factors that regulates the movement of food through the digestive system (gut motility). Beneficial intestinal microbes help support normal gut motility by inhibiting mucosal inflammation, interacting with the nervous system, modulating bile acid metabolism, and altering the intestinal environment through the production of short-chain fatty acids and other compounds (Dimidi 2017; Zhao 2016).

Numerous clinical trials have demonstrated the benefits of probiotic supplements in stimulating gut motility and relieving constipation. A review article reported on five randomized controlled trials using different strains of B. lactis, two trials using L. casei Shirota, and one trial each using L. reuteri DSM 17938 and L. paracasei IMPC 2.1 to manage chronic constipation. The results from all trials were positive, and all but one showed statistically significant improvements. Various benefits were observed, including improved stool consistency and frequency, reduced transit time, and decreased severity of constipation (Zhao 2016). A systematic review and meta-analysis of 14 studies with a combined total of 1,182 adults with constipation found significant benefits with B. lactis, but not L. casei Shirota (Dimidi 2014). The combination of L. plantarum LP01 and B. breve BR03, as well as the single probiotic B. animalis subspecies lactis BS01, have demonstrated positive effects in relieving constipation (Del Piano 2010). Other studies suggest supplements with B. lactis strains shorten transit time, especially in elderly patients with constipation (Martinez-Martinez 2017; Miller 2016; Miller 2013).

Two interesting placebo-controlled trials looked at the effects of the probiotic B. longum BB536, at a dose of 25 or 50 billion CFUs per day for 16 weeks, on bowel function in elderly patients receiving nutrition via a tube to the stomach or small intestine. When only subjects with low bowel movement frequency were considered, a significant increase in bowel movement frequency was noted, and when only those with high bowel movement frequency were considered, a significant decrease in bowel movement frequency was noted. These findings suggest a modulatory effect of this B. longum strain on bowel function (Kondo 2013).

For more information about constipation, please see the Constipation health protocol.

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a chronic digestive disorder characterized by abdominal pain, distension, and altered bowel function, and is frequently associated with depression, anxiety, and high levels of stress. Although there is no clear cause, there is mounting evidence that dysbiosis might be involved, contributing to both digestive and mood symptoms as a result of changes along the gut-brain axis that involve low-grade inflammation, increased gut permeability, and immunological perturbations (Bennet 2015; Quigley 2018; Sinagra 2017; Staudacher 2016; Canavan 2014; Ohman 2010). Although there have been mixed findings, much of the evidence indicates that probiotics reduce symptoms and improve quality of life in IBS sufferers (Didari 2015; Tiequn 2015; Zhang 2016; Sinagra 2017).

A 2016 meta-analysis pooled the results from 21 randomized controlled trials looking at the impact of probiotic therapy in IBS patients. Some of the included trials used probiotic combinations with various species of Lactobacillus and Bifidobacterium, and others used single species. Probiotics effectively improved overall symptoms and quality of life in IBS patients, but were not consistently helpful in relieving specific symptoms. Dosage, which ranged from 60 million to 450 billion CFUs per day, did not appear to influence efficacy, and single-species probiotics appeared to have an advantage over multi-species probiotics in helping improve overall symptoms and quality of life (Zhang 2016). A 2014 systematic review and meta-analysis that included 43 randomized controlled trials also identified an overall positive impact of probiotics in relieving IBS symptoms (Ford 2014).

Probiotics containing only Lactobacillus species were found in another meta-analysis to be almost 18 times more likely to be beneficial than placebo in adults with IBS (Tiequn 2015). Two studies examining the effects of S. cerevisiae CNCM I-3856 on IBS symptoms found a reduction in abdominal pain in those treated with the probiotic relative to placebo (Cayzeele-Decherf 2017). Several placebo-controlled trials have noted improvement in IBS symptoms in patients treated with probiotics containing strains of Bacillus coagulans (Majeed 2016; Hun 2009; Dolin 2009).

For more information about IBS, please see the Irritable Bowel Syndrome health protocol.

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) encompasses two major autoimmune conditions, ulcerative colitis and Crohn's disease. The gut microbial communities in IBD patients have been found to fluctuate more than those of healthy individuals, and dysbiosis together with the associated immune dysfunction and inflammation have been implicated both in the onset of this condition and in its flare-ups (Halfvarson 2017; Fakhoury 2014; DeGruttola 2016; Lane 2017).

Results from several meta-analyses of randomized controlled trials indicate that probiotic supplements in general may safely help patients with ulcerative colitis achieve and maintain remission (Derwa 2017; Ganji-Arjenaki 2018; Fujiya 2014). Although a significant benefit for probiotic use in general has not been demonstrated in Crohn's disease patients, S. boulardii, when added to standard medical treatment for Crohn's disease, was found to reduce some of the symptoms (Plein 1993) and clinical relapses (Guslandi 2000) in two small randomized controlled trials.

Two placebo-controlled trials evaluated the effect of a commercial combination probiotic called VSL#3 in patients with active mild-to-moderate ulcerative colitis being treated with standard therapies. This product contains four Lactobacillus species (L. acidophilus, L. plantarum, L. casei, and L. bulgaricus), three Bifidobacterium species (B. longum, B. breve, and B. infantis), and one Streptococcus species (S. thermophilus) (Matijasic 2016). In both trials, higher rates of clinical response and remission were seen in those treated with VSL#3 compared with placebo (Sood 2009; Tursi 2010). A similar but uncontrolled trial also noted improved response and remission rates with the addition of VSL#3 to standard treatments (Bibiloni 2005). In another clinical trial of patients with moderate-to-severe ulcerative colitis, a combination probiotic containing L. acidophilus, L. salivarius, and B. bifidus added to mesalazine, an anti-inflammatory drug used to treat IBD, showed better improvement than patients receiving only mesalazine (Palumbo 2016).

Several single-species probiotic supplements have also been useful in managing ulcerative colitis. In a placebo-controlled clinical trial, B. longum BB536, at a dose of 200–300 billion CFUs per day, increased the rate of clinical remission and improved the appearance of the colon tissue (Tamaki 2016), and Escherichia coli Nissle 1917 was as effective as mesalazine for preventing relapses in several trials of patients receiving standard medical therapy (Kruis 1997; Rembacken 1999; Kruis 2004); however, it may not be helpful for inducing remission in active cases (Petersen 2014). A clinical trial that enrolled patients with ulcerative colitis found that the probiotic L. rhamnosus GG was as effective as mesalazine or the combination of the two in preventing relapses (Zocco 2006). In addition, findings from a pilot trial suggest S. boulardii, when added to mesalazine, may help induce clinical remission in ulcerative colitis patients who experience mild-to-moderate flare-ups (Guslandi 2003).

For more information about Crohn's disease and ulcerative colitis, please see the Inflammatory Bowel Disease health protocol.

Gastroesophageal Reflux Disease

The esophagus is home to a rich microbial ecosystem and esophageal dysbiosis has been identified in those with gastroesophageal reflux disease (GERD). It is now thought that this dysbiosis may play a role in the progression of GERD to precancerous and cancerous conditions of the esophagus (Yang 2014; Di Pilato 2016). Although it is not clear yet how esophageal dysbiosis might be addressed, it is clear that the usual treatment for GERD—typically proton pump inhibitor (PPI) medications that reduce stomach acid secretion—can lead to a host of health problems in the long term, including intestinal dysbiosis and small intestinal bacterial overgrowth (SIBO) (Del Piano 2012; Lombardo 2010; Fujimori 2015).

Several studies have looked at the impact of using probiotic supplements along with PPIs. In a randomized clinical trial, children with GERD were treated with a PPI plus either a probiotic containing 100 million CFUs of L. reuteri DSM 17938 per day or a placebo. After 12 weeks, SIBO was detected in 6.2% of those who received the probiotic and 56.2% of those who received the placebo (Belei 2018). A similar trial in adults with GERD found that a probiotic containing L. paracasei F19 prevented treatment-related bloating, flatulence, and abdominal pain (Compare 2015).

For more information about GERD, please see the Gastroesophageal Reflux Disease health protocol.

Gastritis and Peptic Ulcer Disease

The most common causes of gastritis and peptic ulcer disease (PUD) are infection with the bacterium Helicobacter pylori and the use of non-steroidal anti-inflammatory medications. Other causes and contributors include certain other medications, smoking, excessive alcohol intake, older age, and stress (Mayo Clinic 2017a; Mayo Clinic 2017b; Fashner 2015; Nordenstedt 2013).

Over half of people worldwide carry gastric H. pylori (Kusters 2006). Most have no symptoms, but for others, H. pylori can trigger changes to the gastric and upper intestinal mucosa, increasing risk of gastric or duodenal ulcer and gastric cancer (Kafshdooz 2017; Ruggiero 2014). When treatment is indicated, standard medical therapy is the use of so-called triple or quadruple therapy—a proton pump inhibitor, with or without a bismuth salt, and two to three antibiotics. The development of H. pylori resistance to many commonly used antibiotics has decreased the efficacy of this approach in recent years (Goderska 2018; Mascellino 2017).

Probiotics may be helpful in gastritis and PUD due to their ability to reduce mucosal inflammation, decrease the binding of H. pylori, and promote a strong immune response against the bacteria. In addition, certain probiotic strains may produce antibacterial molecules that inhibit H. pylori (Goderska 2018; Homan 2015). A number of clinical trials using various probiotics and combinations with no other treatment have shown, while they do not appear to eradicate H. pylori, they can reduce the number of H. pylori organisms (Homan 2015).

A 2016 meta-analysis that pooled data from 30 randomized controlled trials tested probiotic therapy as an add-on to standard therapy for H. pylori infection. The authors concluded probiotics from the Lactobacillus, Bifidobacterium, or Saccharomyces species improved eradication rates and reduced antibiotic-related side effects (Lau, Ward 2016). Other meta-analyses have also found that a range of single- and multi-strain probiotics can improve eradication rates and treatment tolerance (Lu, Yu 2016; McFarland 2016; Zhang 2015).

Probiotics may also be useful in treating gastritis and PUD patients without H. pylori infection. Animal research suggests probiotic therapy may reduce the ulcer-promoting effects of stress (Konturek 2009) and non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen (Senol 2011; Girard 2010). Clinical trials are needed to confirm these benefits in humans and determine the strains and doses most likely to be effective.

For more information about H. pylori, gastritis, and PUD, please see the Peptic Ulcers health protocol.

Dyspepsia and Bloating

Functional dyspepsia is a condition characterized by fullness and stomach pain, especially after eating, for which a cause cannot be identified. Gastric fluid testing has shown that patients with dyspepsia have distinctly different stomach microorganisms than healthy individuals (Igarashi 2017).

In a randomized controlled trial, patients with functional dyspepsia, and not infected with H. pylori, received either yogurt fortified with L. gasseri OLL2716 or an unfortified placebo yogurt. Major symptoms of dyspepsia were eliminated in 35.3% of those receiving the L. gasseri-enriched yogurt and in 17.3% of those receiving the placebo yogurt (Ohtsu 2017). Other researchers have noted that L. gasseri OLL2716 supplementation reversed dysbiosis of gastric fluid, and this was correlated with recovery from dyspepsia (Igarashi 2017; Nakae 2016).

Bloating is a common symptom of digestive disorders but can also occur persistently without a known cause. Probiotic strains such as B. bifidum MIMBb75 and L. plantarum 299v have been shown to relieve IBS-related bloating and distension in randomized controlled trials (Iovino 2014). In people with abdominal bloating without a clear cause, Lactobacillus GG has been reported to be more effective than placebo for reducing severity of bloating (Di Stefano 2004). In addition, Bacillus coagulans GBI-30, 6086 reduced gastrointestinal symptoms in adults with gas-related symptoms but no known digestive disorders (Kalman 2009).

10 Probiotics For Cardiovascular Health

While the cardiovascular system does not appear to have a microbial community of its own, much attention has recently been drawn to the role of the gut microbiome on cardiovascular health and disease. Research has linked gut dysbiosis to atherosclerosis and hypertension (Lau 2017), and some evidence points to a role of gut microbiota in heart failure (Nagatomo 2015). Clinical trials have shown that probiotic and prebiotic supplements can support weight management and improve other metabolic and inflammatory markers correlated with cardiovascular health (He 2017; Upadrasta 2016).

Probiotics and Blood Pressure

Findings from numerous laboratory and animal studies suggest probiotic bacteria and their fermentation byproducts may have beneficial effects in people with high blood pressure. Possible mechanisms for this effect include reducing oxidative stress and systemic inflammation, improving cholesterol metabolism and dietary calcium absorption, and inhibiting the action of a vasoconstrictive enzyme called angiotensin-converting enzyme (ACE) (Daliri 2017; Upadrasta 2016). In a five-year observational study, intake of dairy products fermented with Lactobacillus casei strain Shirota three or more times per week was associated with a reduced risk of developing hypertension (Aoyagi 2017). In a three-week pilot trial in 40 subjects with obesity and hypertension, blood pressures and body mass indices were reduced in those who received a cheese fermented with the probiotic L. plantarum TENSIA compared to cheese without the probiotic bacteria (Sharafedtinov 2013).

Probiotics and Cholesterol Metabolism

A meta-analysis of 13 trials with a combined total of 485 participants found that probiotic therapy in general can effectively reduce total and LDL-cholesterol levels. In this analysis, L. acidophilus strains were found to have strong lipid-reducing effects (Shimizu 2015). Other Lactobacillus bacteria, such as L. reuteri and L. plantarum, have also been shown to reduce total cholesterol and LDL-cholesterol levels in clinical trials (Lau 2017; Shimizu 2015).

In a randomized trial in 127 subjects with high cholesterol levels, taking capsules with 2.9 billion CFUs of the probiotic L. reuteri NCIMB 30242 twice daily led to a 9.1% decrease in total cholesterol levels, an 11.6% decrease in LDL-cholesterol levels, and a 13.4% improvement in LDL- to HDL-cholesterol ratio compared with placebo after nine weeks. The participants receiving L. reuteri NCIMB 30242 also had lower levels of the inflammatory markers C-reactive protein and fibrinogen at the end of the trial (Jones, Martoni, Prakash 2012). In addition, a second analysis of the results from this trial showed that vitamin D levels increased in those receiving probiotic therapy (Jones 2013). Eating yogurt containing L. reuteri NCIMB 30242 for six weeks was also found to lower elevated total and LDL-cholesterol levels in a placebo-controlled trial with 114 participants (Jones, Martoni, Parent 2012).

In another controlled trial in 49 adults with normal to mildly elevated cholesterol levels, a supplement providing 2 billion CFUs of L. plantarum ECGC 13110402 taken twice daily for 12 weeks lowered LDL-cholesterol levels. A subset of participants who were over age 60 years also had improvements in triglyceride and HDL-cholesterol levels after using the probiotic. Reduced blood pressures were also noted in those receiving the probiotic (Costabile 2017).

11 Probiotics For Oral Health

The oral microbiome, a very important component of the human microbiome, contains hundreds to thousands of diverse species that are present in various places, such as on the teeth, gums, cheeks, palate, lips, and tonsils (Arweiler 2016; Dewhirst 2010). Dysbiosis within the oral cavity plays a role in the development of dental cavities, gingivitis, and periodontal disease. A growing body of evidence indicates that restoring healthy populations of beneficial oral bacteria through probiotic therapy can have an important role in preventing and treating these conditions (Gupta 2017; Rosier 2017; Haukioja 2010; Allaker 2017).

Periodontal Disease

Dysbiosis of the oral microbiome is associated with deepening of the periodontal pockets and periodontitis, a chronic inflammatory condition that can damage the soft tissues and bone and, eventually, lead to tooth loss (Gupta 2017; Meuric 2017; Jiao 2014; Deng 2018). Periodontitis also increases the risk of certain systemic diseases including vascular disease, diabetes, and some forms of cancer (Deng 2018). Several studies found that probiotics can reduce gum bleeding and periodontal pocket depth in patients with periodontal disease, and decrease alveolar bone loss in animal models (Allaker 2017; Maekawa 2014; Gatej 2018; Haukioja 2010; Krasse 2006). The benefits of probiotics may be related to their ability to compete with harmful microbes for nutrients, produce molecules that inhibit harmful bacteria, and cause beneficial changes in immune responses (Allaker 2017).

In a randomized controlled trial in patients with periodontal disease, taking a daily capsule containing 10 mg of heat-killed Lactobacillus plantarum L-137 enhanced the effectiveness of scaling and root planing at reducing periodontal pocket depth (Iwasaki 2016). Although the bacteria in this supplement were no longer viable, other studies have shown that the heat-killed form of L. plantarum L-137 has immune-modulating effects (Fujiki 2012), which may have been responsible for its positive impact on periodontal health.

Another promising supplement for periodontal disease is the probiotic strain L. reuteri (Martin-Cabezas 2016; Kumar 2017). Several clinical trials have found that lozenges made with this probiotic species, when added to regular scaling and root planing, reduce plaque formation, gingival bleeding, and pocket depth, and increase the attachment of the gums to the tooth root in patients with chronic periodontal disease (Ince 2015; Teughels 2013; Vivekananda 2010; Szkaradkiewicz 2014; Tekce 2015). In addition, a 2018 randomized controlled trial found that L. reuteri lozenges showed benefits in patients with mucositis and peri-implantitis, two inflammatory conditions that may involve the tissues surrounding a dental implant (Galofre 2018).

The probiotic bacterium L. salivarius WB21 has been found to decrease levels of harmful bacteria in dental plaque (Mayanagi 2009), improve gingival health (Iwamoto 2010), and reduce the risk of periodontal disease (Shimauchi 2008). In other clinical trials, a probiotic mouth rinse containing L. salivarius NK02 improved the effectiveness of scaling and root planing for periodontal disease (Sajedinejad 2017), and a lozenge containing L. rhamnosus GG and Bifidobacterium animalis subspecies lactis BB-12 decreased plaque development and enhanced gum health in healthy subjects (Toiviainen 2015).

Cavities

Streptococcus salivarius M18 is a probiotic organism that has demonstrated antibacterial effects against S. mutans, an oral bacterium implicated in the formation of dental cavities. It has also been shown to produce enzymes that decrease dental plaque accumulation and acidification (Burton 2013). In a randomized controlled trial, risk factors for cavity development improved after 90 days in children treated with a daily lozenge providing at least 1 billion CFUs of S. salivarius M18 (Di Pierro, Zanvit 2015). In another placebo-controlled trial, three months of treatment with oral S. salivarius M18, at a daily dose of 3.6 billion CFUs, led to greater improvements in plaque scores compared with placebo in children with dental cavities. In addition, bacterial analysis showed that the presence of S. mutans was diminished in children with the highest apparent colonization levels of the probiotic strain (Burton 2013).

Various Lactobacillus species have also been found in laboratory studies to inhibit S. mutans (Lin, Chen 2017; Wasfi 2018). Similar benefits were found in clinical studies. In a randomized controlled trial, probiotic mouth rinses containing either Bacillus coagulans or a mixture of L. acidophilus, B. longum, B. lactis, and B. bifidum, were found to both reduce plaque and improve gum health better than a placebo in children (Yousuf 2017). In another randomized controlled trial, daily use of a chewable tablet with three probiotic Streptococcus species resulted in a lower risk of cavities compared with placebo in healthy two- to three-year-old children (Hedayati-Hajikand 2015).

A broad body of research shows that xylitol, a non-digestible sugar alcohol, has prebiotic effects not only in the gut but also in the mouth (Makinen 2010; Nayak 2014). Xylitol, as a supplement and as an ingredient in toothpastes, mouth rinses, chewing gums, and candies, has been found to reduce levels of cavity-causing bacteria in the saliva and plaque, decrease plaque formation, and inhibit tooth decay (Nayak 2014). A 2017 systematic review and meta-analysis concluded that xylitol is effective for cavity prevention (Janakiram 2017). Another review found that toothpastes with both xylitol and fluoride may protect against cavities more effectively than fluoride-only toothpastes in children (Riley 2015).

For more information about periodontal disease and dental cavities, please see the Oral Health protocol.

12 Probiotics And Skin Health

The skin is home to a large and diverse microbiome that impacts skin health and has body-wide effects on health. The skin microbiome varies in the same individual across body site and also between individuals. It is shaped by both external and internal factors (Prescott 2017; Barnard 2017; SanMiguel 2015; Grice 2011). Yet, even with its exposure to constantly changing conditions, the skin microbiome appears to be largely stable within individuals over time (Oh 2016). Skin dysbiosis has been noted in an array of skin conditions, including atopic dermatitis (eczema), acne, seborrhea, psoriasis, rosacea, and dandruff (Barnard 2017; Abdallah 2017; Paulino 2017).

Probiotic bacteria can have local and systemic effects that support skin barrier function, regulate immune activity, and control microbial populations (Al-Ghazzewi 2014; Wong 2013; Lew 2013). Probiotic supplements may be beneficial in several infectious and inflammatory skin disorders, as well as sun-induced and trauma-related skin damage (Notay 2017; Roudsari 2015; Kober 2015). Most clinical trials have used oral probiotics, but emerging research suggests the topical application of probiotic bacteria may also be useful for promoting skin healing (Zoccali 2016; Lopes 2017).

Acne

Oral probiotics such as Lactobacillus acidophilus and Bifidobacterium bifidum have shown positive effects in people with acne in early clinical research (Bowe 2014). In a controlled trial in 20 subjects with acne, supplementing with L. rhamnosus SP1 at a dose of 3 billion CFUs per day led to greater improvement in skin condition than placebo after 12 weeks (Fabbrocini 2016). Other evidence suggests a combination of oral probiotics and antibiotics may be more effective than either alone for adults with mild-to-moderate acne (Jung 2013). Additional clinical studies found that a 5% L. plantarum topical solution, but not a 1% solution, reduced acne lesion size and redness (Muizzuddin 2012).

The probiotic strain Enterococcus faecalis SL-5, applied as a lotion, demonstrated antibacterial activity against bacteria associated with acne and improved the appearance of acne lesions (Kang 2009). Other probiotic bacteria, including L. reuteri, B. longum, B. adolescentis, and Streptococcus salivarius, have demonstrated similar antibacterial effects and have potential as topical agents for treating acne (Bowe 2014).

Atopic Dermatitis

Factors that shape the intestinal microbiome early in life can influence risk of childhood allergic conditions, such as atopic dermatitis, a skin disorder commonly referred to as eczema (Zheng 2016; Marrs 2016). Atopic dermatitis is associated with impaired skin barrier function, inflammation, and loss of diversity in the skin microbiome (Wollina 2017).

Probiotic supplements may help prevent atopic dermatitis, especially if used during pregnancy and given in the first years of life (Zukiewicz-Sobczak 2014; Kim 2013; Elazab 2013; Pelucchi 2012). In a systematic review and meta-analysis on preventing eczema in infants and children, most studies that were examined used supplements with Lactobacillus species, Bifidobacterium species, or both, and both strains showed protective effects (Mansfield 2014).

According to recent meta-analyses, probiotics may be beneficial for treating atopic dermatitis in adults and in children older than one year (Kim 2014; Huang 2017). Probiotics with Bifidobacterium species alone appear to be less effective than those with mixed species and with Lactobacillus species (Kim 2014; Chang 2016). Three studies showed that L. acidophilus L-92 ameliorated atopic dermatitis in three human studies (Torii 2011; Yamamoto 2016; Inoue 2014).

For more information about acne, atopic dermatitis, and other skin conditions, please see the Skin Disorders health protocol.

13 Probiotics For Vaginal And Urinary Health

Lactobacillus bacteria have long been considered a key component of a healthy vaginal ecosystem. By maintaining an acidic pH (around 3.5‒4.5), competing for energy sources and binding sites on the vaginal wall, and producing antimicrobial chemicals, Lactobacillus species in particular help control populations of potentially harmful microorganisms that may also be present in the vaginal microbiome (Huang, Fettweis 2014; Vaneechoutte 2017). One of the most common vaginal infections worldwide is bacterial vaginosis, which is often referred to not as an infection but as dysbiosis, because the mechanisms underlying the condition are not well understood, and several hypotheses were proposed (Muzny 2016). Vaginal dysbiosis is characterized by a vaginal microbial community that contains fewer Lactobacilli and the overgrowth of other, potentially harmful species, and has been associated with health problems, including increased risk of acquiring and transmitting sexually transmitted infections and preterm birth (van de Wijgert 2017; Mitra 2016). In addition, vaginal dysbiosis has been associated with an increased risk of urinary tract infections (Kirjavainen 2009).

Pilot trials in healthy women indicate that both oral and vaginal administration of Lactobacillus probiotic combinations with species such as L. casei rhamnosus, L. rhamnosus, L. paracasei, L. fermentum, L. plantarum, and L. gasseri may lead to long-term vaginal colonization by Lactobacillus bacteria (Verdenelli 2016; Bohbot 2012; Strus 2012). A 2016 systematic review of 20 studies indicate probiotics containing at least one Lactobacillus species can be an important part of prevention and treatment for bacterial vaginosis and urinary tract infections in women (Hanson 2016). More recent findings even suggest long-term Lactobacillus supplementation may help to clear infection with human papilloma virus (HPV), some strains of which cause cancerous changes in the cervix (Palma 2018).

Bacterial Vaginosis

Bacterial vaginosis is typically treated with antimicrobials, but the recurrence rate is high, at 30%–40%. Adding oral or vaginal Lactobacillus-based probiotic therapy to standard care has been shown to prevent recurrences and improve the success of treatment (Parma 2014; Kumar 2011; Homayouni 2014; Cribby 2008). A 2018 clinical trial in 34 women with bacterial vaginosis compared probiotic therapy with placebo as follow-up treatment after antibiotics. Women in the probiotic group ate a fortified yogurt providing L. crispatus LbV 88, L. gasseri LbV 150N, L. jensenii LbV 116, and L. rhamnosus LbV 96, each at 1.25 billion CFUs per day, and those in the placebo group consumed chemically acidified milk. After four weeks, none of the 17 women in the probiotic group and six of the 17 women in the placebo group had bacterial vaginosis (Laue 2018). A meta-analysis of 12 randomized clinical trials found that including probiotics in bacterial vaginosis treatments may increase cure rates by 53% or more (Huang, Song 2014).

Probiotics are also effective as a stand-alone treatment for bacterial vaginosis in some women. In 544 otherwise healthy women diagnosed with bacterial vaginosis, treatment with an oral probiotic providing 2 billion CFUs of L. rhamnosus GR-1 and L. reuteri RC-14 per day was more effective than placebo for achieving and maintaining a healthy vaginal microbial balance. In this study, almost 62% of probiotic-treated women and nearly 27% of those receiving placebo no longer had bacterial vaginosis after six weeks of treatment, and a normal balance of vaginal microflora was still present in about 51% of women in the probiotic group and about 21% of those in the placebo group six weeks after the end of the treatment (Vujic 2013).

In another clinical study, 34 pre-menopausal women with bacterial vaginosis used slow-release vaginal probiotic tablets with L. fermentum LF15 and L. plantarum LP01 or a placebo nightly for seven nights, then once every three nights for three weeks, and finally once weekly for four more weeks. At the end of the eight weeks, 20 of 24 women in the probiotic group (83%) no longer had bacterial vaginosis, and none of those in the placebo group experienced significant improvement (Vicariotto 2014).

Vulvovaginal Candidiasis

Probiotic Lactobacillus bacteria have been shown to exert antifungal effects and regulate the immune response against Candida yeast species in laboratory research (Chew 2015; Deidda 2016; Wagner 2012). Certain probiotic strains, such as L. rhamnosus GR-1 and L. reuteri RC-14, may alter the metabolic activity of yeast cells and even affect the function of some genes that contribute to antifungal medication resistance (Kohler 2012).

Findings from several studies demonstrate that oral and vaginal Lactobacillus probiotics enhance the effectiveness of standard antifungal treatment in women with vulvovaginal candidiasis. In a randomized placebo-controlled trial, 55 women who underwent standard medical treatment for vulvovaginal candidiasis received additional treatment with oral probiotics, providing 2 billion CFUs of L. rhamnosus GR-1 and L. reuteri RC-14, or placebo, daily for four weeks. At the end of the trial, the probiotic group had fewer symptoms and a lower presence of vaginal yeast compared with the placebo group (Martinez 2009).

In a randomized open-label study, 207 subjects with vaginal candidiasis were treated with standard antifungal medication alone and 209 were treated with medication plus 10 applications of a vaginal probiotic containing L. acidophilus, L. rhamnosus, Streptococcus thermophilus, and L. delbrueckii subspecies bulgaricus, beginning five days after completing medical treatment. At the end of the study, about 69% of those given probiotics did not have clinical complaints compared to about 20% of those treated with antifungal medication alone (Kovachev 2015). Vaginal probiotics containing single strains of L. plantarum have also been shown to decrease recurrence rates after conventional antifungal treatments (Palacios 2016; De Seta 2014).

For more information about vulvovaginal candidiasis, please see the Fungal Infections health protocol.

Urinary Tract Infection

Lactobacillus may inhibit colonization by infection-causing microbes near the urinary opening and enhance immune function, reducing the risk of urinary tract infection. Probiotic therapy with Lactobacillus species may be effective for preventing urinary tract infection (Foxman 2013).

In a one-year clinical trial, 252 postmenopausal women with recurrent urinary tract infections were treated preventively with either a combination oral probiotic, providing 2 billion CFUs of L. rhamnosus GR-1 and L. reuteri RC-14 per day, or trimethoprim-sulfamethoxazole, a combination of two antimicrobials. The mean number of symptomatic urinary tract infections per year dropped in both groups, but the rate of antimicrobial resistance increased substantially in the antimicrobial-treated group. The authors noted that even though the probiotic combination did not decrease the mean number of urinary tract infections more than the antimicrobial treatment, the substantially lower antimicrobial resistance in the probiotic group would make them an acceptable alternative for preventing urinary tract infections (Beerepoot 2012).

L. crispatus is one of the several beneficial Lactobacillus species found in healthy vaginal microbiomes (Lepargneur 2016; Abdelmaksoud 2016). In a pilot study, nine women with recurrent urinary tract infections were treated with a vaginal suppository containing 100 million CFUs of L. crispatus GAI 98322 every two nights for a year. The average number of infections decreased significantly from an average of 5 in the year prior to the trial to an average of 1.3 during the trial (Uehara 2006). In a randomized controlled trial, 100 women with recurrent urinary tract infections were treated with either a vaginal suppository containing 100 million CFUs of L. crispatus CTV-05 or a placebo every night for five nights and then weekly for 10 weeks. Compared with placebo, probiotic therapy reduced the incidence of urinary tract infection episodes during the trial by approximately half (Stapleton 2011).

For more information about urinary tract infection, please see the Urinary Tract Infection health protocol.

14 Probiotics For Respiratory And Immune Health

The microbial residents of the throat, nose, and sinuses make up the upper respiratory microbiome and, much like the gut microbiome, help restrict the presence of harmful microbes and regulate immune function (Schenck 2016; de Steenhuijsen Piters 2015; Gao 2014). Healthy lungs, once thought to be sterile, are now one of the latest body sites known to be home to a unique microbiome (Roux 2017; Pichon 2017; Cui 2014). Some similarities with the oral and nasal microbial communities suggest that certain bacteria may be inhaled from these locations, but the lung also contains specific resident microbes (Hauptmann 2016). The lung microbiome is suspected to play important roles in health and disease, and in regulating immunity. Understanding these links is still at a very early stage (Wang, Li 2017; Cui 2014).

Oral probiotics have been found to reduce the frequency and duration of upper respiratory tract infections and the amount of antibiotic needed for treatment (Hao 2015; Quick 2015). In addition, emerging research suggests topical probiotics in the form of nasal sprays may be effective for restoring a healthy microbial balance in the upper airways (Santagati 2015). Pilot trials indicate that nasal sprays with Streptococcus salivarius 24SMB or S. sanguinis may be helpful in children with chronic or recurrent otitis media (Skovbjerg 2009; Marchisio 2015).

Asthma and Allergic Rhinitis

Lung dysbiosis has been reported in people with asthma, where less microbial diversity and changes in the composition of the microbial communities were observed (Chung 2017). Intestinal dysbiosis also appears to play a substantial role in allergy and asthma susceptibility. Factors such as Cesarean birth, formula feeding, and antibiotic exposure early in life, which negatively impact the infant gut microbiome, are associated with higher risks of asthma and allergies (West 2016; Moya-Perez 2017; Kolokotroni 2012).

A specialized dried yeast fermentate from S. cerevisiae (Epicor) has been shown to reduce seasonal allergies in two small studies. In one study, 25 healthy participants consumed Epicor or a placebo daily for five weeks during allergy season. The placebo group experienced increased seasonal allergy frequency, but the Epicor group did not. Interestingly, allergic symptoms returned within 1–2 weeks after the participants stopped taking Epicor (Jensen 2008). In a larger study, daily doses of 500 mg of Epicor or placebo were compared in 96 healthy subjects with a history of seasonal allergies. Subjects in the Epicor group had less severe nasal congestion and runny nose, and used less allergy medication than those taking placebo (Moyad 2009).

Allergies are mediated in part by an immune-signaling protein called immunoglobulin E (IgE). If the immune system produces too much IgE in response to a stimulus, an allergic reaction can ensue. A strain of Lactobacillus acidophilus called L-92 was shown in a preclinical screening study to reduce production of IgE in mice challenged with a pro-allergenic substance (Ishida 2003). Based on these intriguing results, three clinical trials of L. acidophilus L-92 were carried out. First, L-92 was administered to subjects over two allergy seasons. Dosages were 50 billion CFUs twice daily for six weeks during the first season and 20 billion CFUs once weekly during the second season. Twenty-three people participated during season one, and 20 did so during season two. During the first season, L-92 reduced eye-related distress related to allergies by 31%. During the second, a statistically significant reduction in overall allergy-related distress among the subjects receiving L-92 was observed (Ishida, Nakamura, Kanzato, Sawada, Yamamoto 2005). In the second study, 49 participants with allergic rhinitis took either 30 billion CFUs of L-92 or placebo daily for eight weeks. Nasal mucosal swelling decreased by 24% at week eight in the L-92 group. Also, nasal symptom scores decreased 19% in the L-92 group compared with placebo at week eight (Ishida, Nakamura, Kanzato, Sawada, Hirata 2005). In the third and slightly larger study, 80 subjects who had a cedar pollen allergy and were exposed to cedar pollen at baseline took L-92 or placebo for 8 weeks before re-exposure to cedar pollen. L-92 led to a significant reduction in nasal and eye allergy symptoms compared with placebo upon re-exposure (Caplpis Co. Ltd. 2012).

In adults with allergies, the probiotic strain Bifidobacterium longum BB536 reduced some of the symptoms caused by pollen exposure significantly more than placebo (Xiao 2007). In a randomized controlled trial on children with pollen allergies, a mixture of B. longum BB536, B. infantis M-63, and B. breve M-16V significantly improved symptoms and quality of life (Miraglia Del Giudice 2017). In addition, probiotics have enhanced the effectiveness of allergen-specific immunotherapy in asthma and allergy patients (Liu 2016; Jerzynska 2016). In adults with seasonal allergic rhinitis, oral administration of B. lactis NCC2818 improved some immune parameters and allergy symptoms (Singh 2013).

For more information about allergies and asthma, please see the Allergies health protocol.

Upper Respiratory Tract Infections

Preclinical research suggests some probiotic Lactobacillus species can stimulate the antimicrobial immune response in the respiratory tract (Marranzino 2012), and clinical trials have shown their positive effects in preventing upper respiratory tract infections. Randomized controlled trials in healthy young, middle-aged, and elderly adults have shown that cultured milk products fortified with various probiotic strains of L. casei can decrease the incidence and shorten the duration of upper respiratory tract infections (Shida 2017; Fujita 2013; Jespersen 2015). Milk or yogurt products containing probiotic strains of L. paracasei have also been found to decrease upper respiratory tract infection risk in elderly subjects and children (Corsello 2017; Pu 2017). Findings from a small trial in children suggest the probiotic L. brevis KB290, found in a traditional Japanese pickle, has the potential to protect against influenza (Waki 2014).

In a randomized controlled trial, 78 healthy adults reporting high levels of psychological stress received either an oral tablet containing 10 mg of a heat-killed, non-viable form of the bacterial strain L. plantarum L-137 or a placebo daily for 12 weeks. Upper respiratory tract infections were diminished in number, severity, and duration in those receiving L. plantarum L-137. The heat-killed form of this organism has been shown to have immune-modulating actions, which may have contributed to the benefits seen in this study (Hirose 2013).

A randomized controlled trial in 198 college students found that a daily probiotic with at least 1 billion CFUs each of L. rhamnosus GG and B. animalis subspecies lactis BB-12 for 12 weeks reduced median duration and median severity scores of upper respiratory tract infections and the number of school days missed as a result (Smith 2013). B. animalis subspecies lactis BB-12 alone may also be effective in adults when used in capsules or when added to yogurt prior to fermentation (Meng 2016).

A randomized controlled trial in 465 healthy adults found that the single probiotic strain B. animalis subspecies lactis Bl-04, at a dose of 2 billion CFUs per day, prevented upper respiratory tract infections better than placebo or a probiotic combination (West 2014). Another randomized controlled trial in which undergraduate students were treated with probiotics or placebo found that B. bifidum R0071 supplementation reduced sick days due to upper respiratory tract infection (Langkamp-Henken 2015). In elderly subjects, 100 billion CFUs per day of B. longum BB536 reduced the incidence of influenza compared with placebo over a 14-week period (Namba 2010).

S. salivarius is a prominent bacterium in the healthy mouth (Burton 2006). The probiotic strain S. salivarius K12 is able to colonize the mouth and throat and may reduce the incidence of sore throat episodes caused by a common bacterium (Di Pierro 2014). Supplements with this probiotic strain have shown promise in preventing tonsillitis and pharyngitis (throat infections) and in reducing the occurrence and/or severity of otitis media (middle ear infections) (Zupancic 2017). Trials in children indicate S. salivarius K12 can prevent streptococcal throat infections, scarlet fever, and otitis media (Di Pierro, Colombo, Giuliani 2016), even in those with recent or recurrent episodes of streptococcal pharyngitis (strep throat) (Di Pierro, Colombo, Zanvit 2016; Di Pierro 2014; Di Pierro 2012) or otitis media (Di Pierro, Di Pasquale 2015).

In a randomized placebo-controlled trial on 721 participants and carried out over three winter cold seasons, various probiotic-prebiotic mixtures containing organisms such as L. plantarum LP02, L. rhamnosus LR04andLR05, and B. lactis BS01 led to reduced upper respiratory tract infection frequency (Pregliasco 2008).

In a 16-week randomized, double-blind, placebo-controlled clinical trial on 100 individuals between 60 and 74 years old, the administration of 2 billion B. subtilis CU1 spores daily for 10 years, repeated 4 times, with 18-day breaks, decreased the frequency of respiratory infections in a subgroup of 44 of the participants as compared with placebo. Consumption of the probiotics also led to beneficial changes in immune response (Lefevre 2015). B. subtilis CU1 was safe and well tolerated in elderly people, and its administration was not accompanied by any adverse effects (Lefevre 2017).

For more information about upper respiratory infections and the flu, see the Common Cold and Influenza health protocols.

15 Probiotics And Mood

A randomized controlled clinical trial, which examined participants with low urinary free cortisol levels, reported that Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 improved mental well-being, and could have a preventive role against stress-related psychological changes (Messaoudi, Violle 2011).

In a double-blind placebo-controlled clinical trial on human volunteers, a probiotic formulation containing L. helveticus R0052 and B. longum R0175, taken for 30 days, led to beneficial psychological effects, including improvements in scales that measure depression, anger-hostility, and problem solving. This same probiotic combination also reduced anxiety-like behavior in rats (Messaoudi, Lalonde 2011). In another rat model, the combination of probiotics reduced depression scores after a heart attack and restored gut permeability (Arseneault-Breard 2012), and it decreased cell death in various brain regions (Girard 2009). In mice, it prevented brain changes that occur as a result of chronic psychological stress (Ait-Belgnaoui 2014).

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

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