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      Sex, Body Mass Index, and Dietary Fiber Intake Influence the Human Gut Microbiome

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          Abstract

          Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m 2 vs. <25 kg/m 2) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention.

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          Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin.

          Oligofructose and inulin are naturally occurring indigestible carbohydrates. In vitro they selectively stimulate the growth of species of Bifidobacterium, a genus of bacteria considered beneficial to health. This study was designed to determine their effects on the large bowel microflora and colonic function in vivo. Eight subjects participated in a 45-day study during which they ate controlled diets. For the middle 15 days, 15 g.day-1 oligofructose was substituted for 15 g.day-1 sucrose. Four of these subjects went on to a further period with 15 g.day-1 inulin. Bowel habit, transit time, stool composition, breath H2 and CH4, and the predominant genera of colonic bacteria were measured. Both oligofructose and inulin significantly increased bifidobacteria from 8.8 to 9.5 log10 g stool-1 and 9.2 to 10.1 log10 g stool-1, respectively, whereas bacteroides, clostridia, and fusobacteria decreased when subjects were fed oligofructose, and gram-positive cocci decreased when subjects were fed inulin. Total bacterial counts were unchanged. Fecal wet and dry matter, nitrogen, and energy excretion increased with both substrates, as did breath H2. Little change in fecal short-chain fatty acids and breath CH4 was observed. A 15-g.day-1 dietary addition of oligofructose or inulin led to Bifidobacterium becoming the numerically predominant genus in feces. Thus, small changes in diet can alter the balance of colonic bacteria towards a potentially healthier microflora.
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            The role of pH in determining the species composition of the human colonic microbiota.

            The pH of the colonic lumen varies with anatomical site and microbial fermentation of dietary residue. We have investigated the impact of mildly acidic pH, which occurs in the proximal colon, on the growth of different species of human colonic bacteria in pure culture and in the complete microbial community. Growth was determined for 33 representative human colonic bacteria at three initial pH values (approximately 5.5, 6.2 and 6.7) in anaerobic YCFA medium, which includes a mixture of short-chain fatty acids (SCFA) with 0.2% glucose as energy source. Representatives of all eight Bacteroides species tested grew poorly at pH 5.5, as did Escherichia coli, whereas 19 of the 23 gram-positive anaerobes tested gave growth rates at pH 5.5 that were at least 50% of those at pH 6.7. Growth inhibition of B. thetaiotaomicron at pH 5.5 was increased by the presence of the SCFA mix (33 mM acetate, 9 mM propionate and 1 mM each of iso-valerate, valerate and iso-butyrate). Analysis of amplified 16S rRNA sequences demonstrated a major pH-driven shift within a human faecal bacterial community in a continuous flow fermentor. Bacteroides spp. accounted for 27% of 16S rRNA sequences detected at pH 5.5, but 86% of sequences at pH 6.7. Conversely, butyrate-producing gram-positive bacteria related to Eubacterium rectale represented 50% of all 16S rRNA sequences at pH 5.5, but were not detected at pH 6.7. Inhibition of the growth of a major group of gram-negative bacteria at mildly acidic pH apparently creates niches that can be exploited by more low pH-tolerant microorganisms.
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              Obesity and cancer risk: evidence, mechanisms, and recommendations

              Obesity, a growing health problem worldwide, has been associated with the metabolic syndrome, diabetes, cardiovascular disease, hypertension, and other chronic diseases. Recently, the obesity–cancer link has received much attention. Epidemiological studies have shown that obesity is also associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment and increased cancer-related mortality. Biological mechanisms underlying the relationship between obesity and cancer are not well understood. They include modulation of energy balance and calorie restriction, growth factors, multiple signaling pathways, and inflammatory processes. Key among the signaling pathways linking obesity and cancer is the PI3K/Akt/mTOR cascade, which is a target of many of the obesity-associated factors and regulates cell proliferation and survival. Understanding the molecular and cellular mechanisms of the obesity–cancer connection is important in developing potential therapeutics. The link between obesity and cancer underscores the recommendation to maintain a healthy body weight throughout life as one of the most important ways to protect against cancer.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                15 April 2015
                2015
                : 10
                : 4
                : e0124599
                Affiliations
                [1 ]Department of Population Health, New York University School of Medicine, New York, New York, United States of America
                [2 ]New York University Perlmutter Cancer Center, New York, New York, United States of America
                [3 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
                [4 ]Department of Pathology and Laboratory Medicine, New York Veterans Affairs Medical Center, New York, New York, United States of America
                [5 ]Department of Pathology, New York University School of Medicine, New York, New York, United States of America
                [6 ]Department of Medicine, New York University School of Medicine, New York, New York, United States of America
                University of Illinois at Urbana-Champaign, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CD RBH JA. Performed the experiments: LY. Analyzed the data: CD JA. Contributed reagents/materials/analysis tools: RS JJG. Wrote the paper: CD RS JJG ZP RBH JA.

                Article
                PONE-D-14-46703
                10.1371/journal.pone.0124599
                4398427
                25874569
                ddece9e0-8c69-432b-9065-2d93d405f252

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

                History
                : 20 October 2014
                : 13 January 2015
                Page count
                Figures: 4, Tables: 4, Pages: 14
                Funding
                This research was supported in part by grants R03CA159414, R21CA183887, R01CA159036 and UH3CA140233 from the National Cancer Institute ( http://www.cancer.gov/researchandfunding) (JA) and National Institutes of Health Human Microbiome Project ( http://grants.nih.gov/grants/oer.htm) and by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development ( http://www.research.va.gov/) (ZP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                The data are available from the Database of Genotypes and Phenotypes (dbGAP) with accession number phs000884.v1.p1.

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