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Florassist, Fish Oil, and Stomach Health

October 2015

By Life Extension


The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice.

Diet and nutritional status are among the most important modifiable determinants of human health. The nutritional value of food is influenced in part by a person’s gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelations among diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology, and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent metagenomic analysis of the temporal, spatial, and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized and reproduced much of the bacterial diversity of the donor’s microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat, high-sugar “Western” diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle “clinical trials” that test the effects of environmental and genetic factors on the gut microbiota and host physiology. Nearly full-length 16S rRNA gene sequences are deposited in GenBank under the accession numbers GQ491120 to GQ493997.

Sci Transl Med . 2009 Nov 11;1(6):6ra14

Nutrition of the critically ill &#8212; a 21st-century perspective.

Health care-induced diseases constitute a fast-increasing problem. Just one type of these health care-associated infections (HCAI) constitutes the fourth leading cause of death in Western countries. About 25 million individuals worldwide are estimated each year to undergo major surgery, of which approximately 3 million will never return home from the hospital. Furthermore, the quality of life is reported to be significantly impaired for the rest of the lives of those who, during their hospital stay, suffered life-threatening infections/sepsis. Severe infections are strongly associated with a high degree of systemic inflammation in the body, and intimately associated with significantly reduced and malfunctioning GI microbiota, a condition called dysbiosis. Deranged composition and function of the gastrointestinal microbiota, occurring from the mouth to the anus, has been found to cause impaired ability to maintain intact mucosal membrane functions and prevent leakage of
toxins—bacterial endotoxins, as well as whole bacteria or debris of bacteria, the DNA of which are commonly found in most cells of the body, often in adipocytes of obese individuals or in arteriosclerotic plaques. Foods rich in proteotoxins such as gluten, casein and zein, and proteins, have been observed to have endotoxin-like effects that can contribute to dysbiosis. About 75% of the food in the Western diet is of limited or no benefit to the microbiota in the lower gut. Most of it, comprised specifically of refined carbohydrates, is already absorbed in the upper part of the GI tract, and what eventually reaches the large intestine is of limited value, as it contains only small amounts of the minerals, vitamins and other nutrients necessary for maintenance of the microbiota. The consequence is that the microbiota of modern humans is greatly reduced, both in terms of numbers and diversity when compared to the diets of our paleolithic forebears and the individuals living a rural lifestyle today. It is the artificial treatment provided in modern medical care—unfortunately often the only alternative provided—which constitute the main contributors to a poor outcome. These treatments include artificial ventilation, artificial nutrition, hygienic measures, use of skin-penetrating devices, tubes and catheters, frequent use of pharmaceuticals; they are all known to severely impair the microbiomes in various locations of the body, which, to a large extent, are ultimately responsible for a poor outcome. Attempts to reconstitute a normal microbiome by supply of probiotics have often failed as they are almost always undertaken as a complement to—and not as an alternative to—existing treatment schemes, especially those based on antibiotics, but also other pharmaceuticals.

Nutrients. 2013 Jan 14;5(1):162-207

Gut microbiota and its possible relationship with obesity.

Obesity results from alterations in the body’s regulation of energy intake, expenditure, and storage. Recent evidence, primarily from investigations in animal models, suggests that the gut microbiota affects nutrient acquisition and energy regulation. Its composition has also been shown to differ in lean vs obese animals and humans. In this article, we review the published evidence supporting the potential role of the gut microbiota in the development of obesity and explore the role that modifying the gut microbiota may play in its future treatment. Evidence suggests that the metabolic activities of the gut microbiota facilitate the extraction of calories from ingested dietary substances and help to store these calories in host adipose tissue for later use. Furthermore, the gut bacterial flora of obese mice and humans include fewer Bacteroidetes and correspondingly more Firmicutes than that of their lean counterparts, suggesting that differences in caloric extraction of ingested food substances may be due to the composition of the gut microbiota. Bacterial lipopolysaccharide derived from the intestinal microbiota may act as a triggering factor linking inflammation to high-fat diet-induced metabolic syndrome. Interactions among microorganisms in the gut appear to have an important role in host energy homeostasis, with hydrogen-oxidizing methanogens enhancing the metabolism of fermentative bacteria. Existing evidence warrants further investigation of the microbial ecology of the human gut and points to modification of the gut microbiota as one means to treat people who are over-weight or obese.

Mayo Clin Proc. 2008 Apr;83(4):460-9

Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota.

Obesity and associated metabolic disorders are worldwide epidemic. The literature provides new evidence that gut microbiota dysbiosis (at the phyla, genus, or species level) affects host metabolism and energy storage. Here we discuss new findings that may explain how gut microbiota can be involved in the development or in the control of obesity and associated low-grade inflammation. New powerful molecular biology methods and the use of gnotobiotic animal allowed to analyze the molecular link between gut bacteria and the host. Moreover, even if more studies are needed to unravel how changing gut microbiota impacts on the development of obesity and related metabolic alterations, probiotic and prebiotic approach appear as potential interesting treatments to reverse host metabolic alterations linked to gut microbiota dysbiosis.

Curr Opin Pharmacol. 2009 Dec;9(6):737-43

Intestinal microbiota and overweight.

The microbes in our gut can influence our weight by providing us with energy through the degradation of nondigestable carbohydrates and by affecting the cellular energy status of liver and muscle cells and the accumulation of lipids in adipose tissue. Thus, it is not surprising that in several studies the gastrointestinal microbiota of overweight and obese subjects has been found to differ from that of lean subjects. The initial findings linked obesity with proportionally decreased levels of the phylum Bacteroidetes and increased levels of the phylum Firmicutes. Later, several studies have assessed the association between overweight or obesity and the gastrointestinal microbiota, applying an array of molecular methods targeting the microbiota as a whole or specific bacterial groups or species within. However, at present it is difficult to draw conclusions on which of the observed microbiota alterations are relevant; essentially all of the bacterial groups that have been studied in more than one trial have given contradictory results in regard to their association with weight. Some of these discrepancies can result from methodological issues and some from the nature of the gastrointestinal microbiota, which is an extremely complex and dynamic microbial ecosystem with high subject specificity. In addition, selecting subjects purely based on weight may result in a largely heterogeneous group with several potentially confounding factors. While it may be premature to conclude which specific groups of bacteria are prominent in the intestinal tract of overweight and obese subjects, it appears clear that microbes contribute to weight gain and related health issues, such as the metabolic syndrome and type II diabetes. Therefore, it is important to continue to search for common microbial markers and predictors of obesity, and to study how these may be modulated with probiotics and prebiotics to promote health.

Benef Microbes. 2010 Nov;1(4):407-21

Immunosenescence and anti-immunosenescence therapies: the case of probiotics.

Aging is a complex process that negatively impacts the development of the immune system and its ability to function. Progressive changes in the T and B cell systems over the life span have a major impact on the capacity to respond to immune challenge. These cumulative age-associated changes in immune competence are termed immunosenescence. This process is mostly characterized by: (1) shrinkage of the T cell repertoire and accumulation of oligoclonal expansions of memory/effector cells directed toward ubiquitary infectious agents; (2) involution of the thymus and the exhaustion of naive T cells; and (3) chronic inflammatory status. Here we discuss possible strategies to counteract these main aspects of immunosenescence, in particular the role of the normalization of intestinal microflora by probiotics. A better understanding of immunosenescence and the development of new strategies to counteract it are essential for improving the quality of life of the elderly population.

Rejuvenation Res. 2008 Apr;11(2):425-32

The inflammatory status of old age can be nurtured from the intestinal environment.

PURPOSE OF REVIEW: Recent studies suggest an association between inflammation status and the presence of chronic disease in the elderly. The review examines publications that address the low level of chronic inflammation and emphasizes how an altered host-microbiota interaction at the gut level could contribute to maintaining a low systemic inflammatory status in the elderly. RECENT FINDINGS: The first population cross-sectional studies with relevant numbers of healthy elderlies show age-related global changes in gut microbiota with a consistent increase in nonpathogenic Gram-negative mainly Enterobacteria and country-specific changes in bifidobacteria. Noninvasive methods have permitted us to detect subclinical intestinal inflammation in the elderly population. Furthermore, few studies report on immune and/or inflammatory response; however, prebiotics, probiotics or synbiotics might improve the inflammatory condition of the elderly. SUMMARY: A better understanding of the mechanisms of host-gut microbiota cross-talk would significantly help in the design of novel nutritional strategies targeting immune reactivity at the mucosal level.

Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):13-20

Gut changes attributed to ageing: effects on intestinal microflora.

PURPOSE OF REVIEW: There is increased evidence of several impaired gastrointestinal functions with ageing. In the elderly, however, most gastrointestinal functions remain relatively intact because of the large reserve capacity of the intestine and the great secretion capacity of the pancreas. This review will focus on changes in gut microflora observed in the elderly and on the potential benefit of probiotics in this population. RECENT FINDINGS: Recent studies suggest that age affects the intestinal microflora with a decrease in anaerobes and bifidobacteria population and an increase in enterobacteria. These changes and the reduced intestinal immunity of the aged may favour gastrointestinal infections that are frequent in the elderly. Clostridium difficile-associated diarrhoea, one of the most common nosocomial infections in the elderly, has a profound effect on morbidity, mortality and health costs. Probiotics may have interesting positive effects on intestinal function, and the efficacy of treatment with Lactobacilli and Saccharomyces boulardii in Clostridium difficile-associated diarrhoea has been well established in a recent meta-analysis. Studies performed in healthy elderly patients suggest that diet supplementation with probiotics may reduce the impaired immunity associated with ageing. SUMMARY: Important changes in intestinal microflora of the elderly have recently been demonstrated and may have important clinical consequences. Further studies should be conducted to determine if the consumption of probiotics is associated with a lower infection rate and a higher effectiveness of vaccines.

Curr Opin Clin Nutr Metab Care. 2003 Jan;6(1):49-54

The inflammatory status of the elderly: the intestinal contribution.

A common finding in the elderly population is a chronic subclinical inflammatory status that coexists with immune dysfunction. These interconnected processes are of sufficient magnitude to impact health and survival time. In this review we discuss the different signals that may stimulate the inflammatory process in the aging population as well as the molecular and cellular components that can participate in the initiation, the modulation or termination of the said process. A special interest has been devoted to the intestine as a source of signals that can amplify local and systemic inflammation. Sentinel cells in the splanchnic area are normally exposed to more than one stimulus at a given time. In the intestine of the elderly, endogenous molecules produced by the cellular aging process and stress as well as exogenous evolutionarily conserved molecules from bacteria, are integrated into a network of receptors and molecular signalling pathways that result in chronic inflammatory activation. It is thus possible that nutritional interventions which modify the intestinal ecology can diminish the pro-inflammatory effects of the microbiota and thereby reinforce the mucosal barrier or modulate the cellular activation pathways.

Mutat Res. 2010 Aug 7;690(1-2):50-6

Human intestinal microbiota and healthy ageing.

Earlier studies have indicated a decrease in anaerobes and bifidobacteria and a concomitant increase in enterobacteria in the intestinal microbiota with ageing. However, new data obtained with molecular techniques suggests decreased stability and increased diversity of the gut microbiota with advancing age. Further, no simple marker change in microbiota composition can be identified. Except for the reduced immune function, ageing itself may have relatively little effect on overall gastrointestinal function. Concomitant changes in nutrition, increased incidence of disease and corresponding use of medication with advancing age modify the composition of the microbial community of the gastrointestinal tract. This mini-review will focus on the recent findings on the gut microbiota of the elderly and on the potential benefits of probiotics, prebiotics and synbiotics.

Ageing Res Rev. 2010 Apr;9(2):107-16

The interplay between the intestinal microbiota and the brain.

The intestinal microbiota consists of a vast bacterial community that resides primarily in the lower gut and lives in a symbiotic relationship with the host. A bidirectional neurohumoral communication system, known as the gut-brain axis, integrates the host gut and brain activities. Here, we describe the recent advances in our understanding of how the intestinal microbiota communicates with the brain via this axis to influence brain development and behaviour. We also review how this extended communication system might influence a broad spectrum of diseases, including irritable bowel syndrome, psychiatric disorders and demyelinating conditions such as multiple sclerosis.

Nat Rev Microbiol. 2012 Nov;10(11):735-42

Intestinal microbiota in functional bowel disorders: a Rome foundation report.

It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.

Gut . 2013 Jan;62(1):159-76

Spatial and temporal variability of the human microbiota.

The knowledge that our bodies are home to microbes is not new; van Leeuwenhoek first saw the microbes of the mouth and gut over three centuries ago. However, next generation sequencing technologies are enabling us to characterize our microbial consortia on an unprecedented scale, and are providing new insights into the range of variability of our microbiota and their contributions to our health. The microbiota far outnumber the human component of our selves, with 10 times more cells and at least 100 times more genes. Moreover, while individuals share over 99.9% of their human genome sequence, there are vast differences in the microbiome (the collection of genes of our associated microbes). This raises the question of the extent to which our microbial community determines our human physiological responses and susceptibility to disease. In order to develop technologies that allow us to manipulate the microbiome to improve health we must first understand the factors that influence spatial and temporal variation, stability in response to perturbation, and conditions that induce community-wide changes.

Clin Microbiol Infect. 2012 Jul;18 Suppl 4:8-11

Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses.

The lining of the gastrointestinal tract is the largest vulnerable surface that faces the external environment. Just as the other large external surface, the skin, is regarded as a sensory organ, so should the intestinal mucosa. In fact, the mucosa has three types of detectors: neurons, endocrine cells, and immune cells. The mucosa is in immediate contact with the intestinal contents so that nutrients can be efficiently absorbed, and, at the same time, it protects against the intrusion of harmful entities, such as toxins and bacteria, that may enter the digestive system with food. Signals are sent locally to control motility, secretion, tissue defense, and vascular perfusion; to other digestive organs, for example, to the stomach, gallbladder, and pancreas; and to the central nervous system, for example to influence feeding behavior. The three detecting systems in the intestine are more extensive than those of any other organ: the enteric nervous system contains on the order of 10(8) neurons, the gastroenteropancreatic endocrine system uses more than 20 identified hormones, and the gut immune system has 70-80% of the body’s immune cells. The gastrointestinal tract has an integrated response to changes in its luminal contents. When this response is maladjusted or is overwhelmed, the consequences can be severe, as in cholera intoxication, or debilitating, as in irritable bowel syndrome. Thus it is essential to obtain a full understanding of the sensory functions of the intestine, of how the body reacts to the information, and of how neural, hormonal, and immune signals interact.

Am J Physiol. 1999 Nov;277(5 Pt 1):G922-8