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      Infant Gut Microbiota Development Is Driven by Transition to Family Foods Independent of Maternal Obesity

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          Abstract

          The potential influence of maternal obesity on infant gut microbiota may occur either through vertically transmitted microbes or through the dietary habits of the family. Recent studies have suggested that the heritability of obesity may partly be caused by the transmission of “obesogenic” gut microbes. However, the findings presented here suggest that maternal obesity per se does not affect the overall composition of the gut microbiota and its development after introduction of complementary foods. Rather, progression in complementary feeding is found to be the major determinant for gut microbiota establishment. Expanding our understanding of the influence of complementary diet on the development and establishment of the gut microbiota will provide us with the knowledge to tailor a beneficial progression of our intestinal microbial community.

          ABSTRACT

          The first years of life are paramount in establishing our endogenous gut microbiota, which is strongly affected by diet and has repeatedly been linked with obesity. However, very few studies have addressed the influence of maternal obesity on infant gut microbiota, which may occur either through vertically transmitted microbes or through the dietary habits of the family. Additionally, very little is known about the effect of diet during the complementary feeding period, which is potentially important for gut microbiota development. Here, the gut microbiotas of two different cohorts of infants, born either of a random sample of healthy mothers ( n = 114), or of obese mothers ( n = 113), were profiled by 16S rRNA amplicon sequencing. Gut microbiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal obesity did not influence microbial diversity or specific taxon abundances during the complementary feeding period. Across cohorts, breastfeeding duration and composition of the complementary diet were found to be the major determinants of gut microbiota development. In both cohorts, gut microbial composition and alpha diversity were thus strongly affected by introduction of family foods with high protein and fiber contents. Specifically, intake of meats, cheeses, and Danish rye bread, rich in protein and fiber, were associated with increased alpha diversity. Our results reveal that the transition from early infant feeding to family foods is a major determinant for gut microbiota development.

          IMPORTANCE The potential influence of maternal obesity on infant gut microbiota may occur either through vertically transmitted microbes or through the dietary habits of the family. Recent studies have suggested that the heritability of obesity may partly be caused by the transmission of “obesogenic” gut microbes. However, the findings presented here suggest that maternal obesity per se does not affect the overall composition of the gut microbiota and its development after introduction of complementary foods. Rather, progression in complementary feeding is found to be the major determinant for gut microbiota establishment. Expanding our understanding of the influence of complementary diet on the development and establishment of the gut microbiota will provide us with the knowledge to tailor a beneficial progression of our intestinal microbial community.

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          Comparative Analysis of Pyrosequencing and a Phylogenetic Microarray for Exploring Microbial Community Structures in the Human Distal Intestine

          Background Variations in the composition of the human intestinal microbiota are linked to diverse health conditions. High-throughput molecular technologies have recently elucidated microbial community structure at much higher resolution than was previously possible. Here we compare two such methods, pyrosequencing and a phylogenetic array, and evaluate classifications based on two variable 16S rRNA gene regions. Methods and Findings Over 1.75 million amplicon sequences were generated from the V4 and V6 regions of 16S rRNA genes in bacterial DNA extracted from four fecal samples of elderly individuals. The phylotype richness, for individual samples, was 1,400–1,800 for V4 reads and 12,500 for V6 reads, and 5,200 unique phylotypes when combining V4 reads from all samples. The RDP-classifier was more efficient for the V4 than for the far less conserved and shorter V6 region, but differences in community structure also affected efficiency. Even when analyzing only 20% of the reads, the majority of the microbial diversity was captured in two samples tested. DNA from the four samples was hybridized against the Human Intestinal Tract (HIT) Chip, a phylogenetic microarray for community profiling. Comparison of clustering of genus counts from pyrosequencing and HITChip data revealed highly similar profiles. Furthermore, correlations of sequence abundance and hybridization signal intensities were very high for lower-order ranks, but lower at family-level, which was probably due to ambiguous taxonomic groupings. Conclusions The RDP-classifier consistently assigned most V4 sequences from human intestinal samples down to genus-level with good accuracy and speed. This is the deepest sequencing of single gastrointestinal samples reported to date, but microbial richness levels have still not leveled out. A majority of these diversities can also be captured with five times lower sampling-depth. HITChip hybridizations and resulting community profiles correlate well with pyrosequencing-based compositions, especially for lower-order ranks, indicating high robustness of both approaches. However, incompatible grouping schemes make exact comparison difficult.
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            Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants.

            Fecal samples were obtained from a cohort of 330 healthy Danish infants at 9, 18, and 36 months after birth, enabling characterization of interbacterial relationships by use of quantitative PCR targeting 31 selected bacterial 16S rRNA gene targets representing different phylogenetic levels. Nutritional parameters and measures of growth and body composition were determined and investigated in relation to the observed development in microbiota composition. We found that significant changes in the gut microbiota occurred, particularly from age 9 to 18 months, when cessation of breastfeeding and introduction of a complementary feeding induce replacement of a microbiota characterized by lactobacilli, bifidobacteria, and Enterobacteriaceae with a microbiota dominated by Clostridium spp. and Bacteroides spp. Classification of samples by a proxy enterotype based on the relative levels of Bacteroides spp. and Prevotella spp. showed that enterotype establishment occurs between 9 and 36 months. Thirty percent of the individuals shifted enterotype between 18 and 36 months. The composition of the microbiota was most pronouncedly influenced by the time of cessation of breastfeeding. From 9 to 18 months, a positive correlation was observed between the increase in body mass index and the increase of the short-chain-fatty-acid-producing clostridia, the Clostridum leptum group, and Eubacterium hallii. Considering previously established positive associations between rapid infant weight gain, early breastfeeding discontinuation, and later-life obesity, the corresponding microbial findings seen here warrant attention.
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              Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut.

              The human gut is home to trillions of microbes, thousands of bacterial phylotypes, as well as hydrogen-consuming methanogenic archaea. Studies in gnotobiotic mice indicate that Methanobrevibacter smithii, the dominant archaeon in the human gut ecosystem, affects the specificity and efficiency of bacterial digestion of dietary polysaccharides, thereby influencing host calorie harvest and adiposity. Metagenomic studies of the gut microbial communities of genetically obese mice and their lean littermates have shown that the former contain an enhanced representation of genes involved in polysaccharide degradation, possess more archaea, and exhibit a greater capacity to promote adiposity when transplanted into germ-free recipients. These findings have led to the hypothesis that M. smithii may be a therapeutic target for reducing energy harvest in obese humans. To explore this possibility, we have sequenced its 1,853,160-bp genome and compared it to other human gut-associated M. smithii strains and other Archaea. We have also examined M. smithii's transcriptome and metabolome in gnotobiotic mice that do or do not harbor Bacteroides thetaiotaomicron, a prominent saccharolytic bacterial member of our gut microbiota. Our results indicate that M. smithii is well equipped to persist in the distal intestine through (i) production of surface glycans resembling those found in the gut mucosa, (ii) regulated expression of adhesin-like proteins, (iii) consumption of a variety of fermentation products produced by saccharolytic bacteria, and (iv) effective competition for nitrogenous nutrient pools. These findings provide a framework for designing strategies to change the representation and/or properties of M. smithii in the human gut microbiota.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                mSphere
                mSphere
                msph
                msph
                mSphere
                mSphere
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2379-5042
                10 February 2016
                Jan-Feb 2016
                : 1
                : 1
                : e00069-15
                Affiliations
                [a ]National Food Institute, Technical University of Denmark, Søborg, Denmark
                [b ]Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
                University of Wisconsin, Madison
                Author notes
                Address correspondence to Tine Rask Licht, trli@ 123456food.dtu.dk .

                Citation Laursen MF, Andersen LBB, Michaelsen KF, Mølgaard C, Trolle E, Bahl MI, Licht TR. 2016. Infant gut microbiota development is driven by transition to family foods independent of maternal obesity. mSphere 1(1):e00069-15. doi: 10.1128/mSphere.00069-15.

                Author information
                http://orcid.org/0000-0002-6399-9574
                Article
                mSphere00069-15
                10.1128/mSphere.00069-15
                4863607
                27303699
                7a0e8db9-4660-40d2-bbfa-31d34d52eaea
                Copyright © 2016 Laursen et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 25 November 2015
                : 6 January 2016
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 59, Pages: 16, Words: 11263
                Funding
                Funded by: Danish Council for Strategic Research
                Award ID: 0603-00579b
                Award Recipient : Kim F. Michaelsen
                Funded by: Danish Council for Strategic Research
                Award ID: 11-116163
                Award Recipient : Tine Rask Licht
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Host-Microbe Biology
                Editor's Pick
                Custom metadata
                January/February 2016

                16s rrna sequencing,breastfeeding,complementary diet,family foods,infant gut microbiota,maternal obesity

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