Abstract
The human microbiome has been associated with health status, and risk of disease development. While the etiology of microbiome-mediated disease remains to be fully elucidated, one mechanism may be through microbial metabolism. Metabolites produced by commensal organisms, including in response to host diet, may affect host metabolic processes, with potentially protective or pathogenic consequences. We conducted multi-omic phenotyping of healthy subjects (N = 136), in order to investigate the interaction between diet, the microbiome, and the metabolome in a cross-sectional sample. We analyzed the nutrient composition of self-reported diet (3-day food records and food frequency questionnaires). We profiled the gut and oral microbiome (16S rRNA) from stool and saliva, and applied metabolomic profiling to plasma and stool samples in a subset of individuals (N = 75). We analyzed these multi-omic data to investigate the relationship between diet, the microbiome, and the gut and circulating metabolome. On a global level, we observed significant relationships, particularly between long-term diet, the gut microbiome and the metabolome. Intake of plant-derived nutrients as well as consumption of artificial sweeteners were associated with significant differences in circulating metabolites, particularly bile acids, which were dependent on gut enterotype, indicating that microbiome composition mediates the effect of diet on host physiology. Our analysis identifies dietary compounds and phytochemicals that may modulate bacterial abundance within the gut and interact with microbiome composition to alter host metabolism.
Highlights
The human microbiome is a complex ecosystem of bacteria, viruses, fungi, and bacteriophages, which interact with each other and their host (Sears, 2005; Goodman and Gordon, 2010; Minot et al, 2011)
We focused on pairs of diet-metabolite variables linked to at least one common genus identified by the log-contrast model in section 2.7, and applied mediation analysis to the diet-gut microbiomemetabolite triplet
No global associations were detected between diet, the microbiome, or metabolome, and demographic variables
Summary
The human microbiome is a complex ecosystem of bacteria, viruses, fungi, and bacteriophages, which interact with each other and their host (Sears, 2005; Goodman and Gordon, 2010; Minot et al, 2011). Microbiome composition is unique to an individual, is established early in life, and plays a crucial role in lifelong health (Kau et al, 2011; Minot et al, 2011; Maynard et al, 2012; Koren et al, 2013; Mohammadkhah et al, 2018). There is considerable site-specificity in microbiome composition, with distinct populations residing within each body site of an individual (Faust et al, 2012; Ding and Schloss, 2014). The gut microbiome, in combination with habitual diet, is likely to play a major role in determining gut mucosal membrane permeability and influencing systemic inflammation (Moreira et al, 2012; Pendyala et al, 2012)
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