Dataset Information

Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

ABSTRACT: Although the gut microbiome plays important roles in host physiology, health and disease, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut. We used the genetically diverse Collaborative Cross mouse system to discover that early life history impacts the microbiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity. Correlations between specific operational taxonomic units (OTUs) and B-cell counts, body weight and neuromuscular function (rotarod performance) were also observed. This study is the first to determine and rank the complex contributions of built environment, host genetics and diet in shaping gut microbial and metabolite composition, host fitness and behavior.

INSTRUMENT(S): 5975C Series GC/MSD (Agilent)

SUBMITTER: Tom Metz

PROVIDER: MTBLS345 | MetaboLights | 2016-10-05

REPOSITORIES: MetaboLights

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Publications

Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome.

Snijders Antoine M AM Langley Sasha A SA Kim Young-Mo YM Brislawn Colin J CJ Noecker Cecilia C Zink Erika M EM Fansler Sarah J SJ Casey Cameron P CP Miller Darla R DR Huang Yurong Y Karpen Gary H GH Celniker Susan E SE Brown James B JB Borenstein Elhanan E Jansson Janet K JK Metz Thomas O TO Mao Jian-Hua JH

Nature microbiology 20161128

Although the gut microbiome plays important roles in host physiology, health and disease<sup>1</sup>, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut. We used the genetically diverse Collaborative Cross mouse system<sup>2</sup> to discover that early life history impacts the microbiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mo ...[more]

PMID: 27892936

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Project description:Genome scale metabolic model of Drosophila gut microbe Acetobacter fabarum Abstract - An important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and their impact on host physiology. This research can be confounded by poorly understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multiway interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the Drosophila gut microbiome (from single taxa to the five-member community of Acetobacter and Lactobacillus species) under three nutrient regimes. We show that the metabolic function of Drosophila gut bacteria is dynamic, influenced by community composition, and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that, in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle, including 2-oxoglutarate and succinate, are produced at high flux and cross-fed between bacterial taxa, suggesting important roles for TCA cycle intermediates in modulating Drosophila gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the host.IMPORTANCE Drosophila is an important model for microbiome research partly because of the low complexity of its mostly culturable gut microbiota. Our current understanding of how Drosophila interacts with its gut microbes and how these interactions influence host traits derives almost entirely from empirical studies that focus on individual microbial taxa or classes of metabolites. These studies have failed to capture fully the complexity of metabolic interactions that occur between host and microbe. To overcome this limitation, we reconstructed and analyzed 31 metabolic models for every combination of the five principal bacterial taxa in the gut microbiome of Drosophila This revealed that metabolic interactions between Drosophila gut bacterial taxa are highly dynamic and influenced by cooccurring bacteria and nutrient availability. Our results generate testable hypotheses about among-microbe ecological interactions in the Drosophila gut and the diversity of metabolites available to influence host traits.

Dataset Information

Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

Publications

Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome.

Similar Datasets

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