Maintaining a Healthy Microbiome
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).
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).
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).
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).