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      The early infant gut microbiome varies in association with a maternal high-fat diet

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          Abstract

          Background

          Emerging evidence suggests that the in utero environment is not sterile as once presumed. Work in the mouse demonstrated transmission of commensal bacteria from mother to fetus during gestation, though it is unclear what modulates this process. We have previously shown in the nonhuman primate that, independent of obesity, a maternal high-fat diet during gestation and lactation persistently shapes the juvenile gut microbiome. We therefore sought to interrogate in a population-based human longitudinal cohort whether a maternal high-fat diet similarly alters the neonatal and infant gut microbiome in early life.

          Methods

          A representative cohort was prospectively enrolled either in the early third trimester or intrapartum ( n = 163), with a subset consented to longitudinal sampling through the postpartum interval ( n = 81). Multiple body site samples, including stool and meconium, were collected from neonates at delivery and by 6 weeks of age. A rapid dietary questionnaire was administered to estimate intake of fat, added sugars, and fiber over the past month (National Health and Examination Survey). DNA was extracted from each infant meconium/stool sample (MoBio) and subjected to 16S rRNA gene sequencing and analysis.

          Results

          On average, the maternal dietary intake of fat ranged from 14.0 to 55.2 %, with an average intake of 33.1 % (σ = 6.1 %). Mothers whose diets significantly differed from the mean (±1 standard deviation) were separated into two distinct groups, a control group ( n = 13, μ = 24.4 %) and a high-fat group ( n = 13, μ = 43.1 %). Principal coordinate analysis revealed that the microbiome of the neonatal stool at birth (meconium) clustered differently by virtue of maternal gestational diet (PERMANOVA p = 0.001). LEfSe feature selection identified several taxa that discriminated the groups, with a notable relative depletion of Bacteroides in the neonates exposed to a maternal high-fat gestational diet (Student’s t-test, p < 0.05) that persisted to 6 weeks of age.

          Conclusions

          Similar to the primate, independent of maternal body mass index, a maternal high-fat diet is associated with distinct changes in the neonatal gut microbiome at birth which persist through 4–6 weeks of age. Our findings underscore the importance of counseling pregnant mothers on macronutrient consumption during pregnancy and lactation.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13073-016-0330-z) contains supplementary material, which is available to authorized users.

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          Most cited references59

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          Metagenomic biomarker discovery and explanation

          This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
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            Structure, Function and Diversity of the Healthy Human Microbiome

            Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin, and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics, and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analyzed the largest cohort and set of distinct, clinically relevant body habitats to date. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology, and translational applications of the human microbiome.
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              Diet rapidly and reproducibly alters the human gut microbiome

              Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut 1–5 , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals 2 , reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease 6 . In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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                Author and article information

                Contributors
                713 798-8467 , aagaardt@bcm.edu
                Journal
                Genome Med
                Genome Med
                Genome Medicine
                BioMed Central (London )
                1756-994X
                9 August 2016
                9 August 2016
                2016
                : 8
                : 77
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX USA
                [2 ]Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX USA
                [3 ]Medical Scientist Training Program, Baylor College of Medicine, Houston, TX USA
                [4 ]Departments of Molecular & Human Genetics, Molecular & Cell Biology, and Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX USA
                [5 ]Division of Maternal-Fetal Medicine, Baylor College of Medicine, One Baylor Plaza, Jones 314, Houston, TX 77030 USA
                Article
                330
                10.1186/s13073-016-0330-z
                4977686
                27503374
                38d07eba-c377-4306-b050-b7d794fc5c18
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 April 2016
                : 1 July 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000056, National Institute of Nursing Research;
                Award ID: NR014792-01
                Award Recipient :
                Funded by: National Institutes of Health (US)
                Award ID: DP2 DP21DP2OD001500
                Award ID: N01-HD-80020
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: T32 GM007330
                Award ID: T32GM088129
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Molecular medicine
                high-fat diet,maternal gestational diet,microbiome,neonatal microbiome development

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