Multi-Omic Analysis of the Microbiome and Metabolome in Healthy Subjects Reveals Microbiome-Dependent Relationships Between Diet and Metabolites

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.

An Integrative Approach to Assessing Diet–Cancer Relationships

“…Tang and colleagues [51] applied metabolomics and metagenomics analyses to study usual dietary intake in healthy participants (Table 1). In addition to identifying associations between diet and metabolites, they conducted analyses to define inter-relationships between diet, the microbiome and metabolome and additional analyses to determine whether identified associations were mediated by microbial enterotype.…”

Another look at microbe–metabolite interactions: how scale invariant correlations can outperform a neural network

“…Many scientists are now interested in studying the correlative relationships between microbes and metabolites (e.g., [1,2,3,4]). However, these kinds of analyses are complicated by the compositional (i.e., relative) nature of the data [5,6].…”

Dynamic alterations in rumen bacterial community and metabolome characteristics in response to feed nutrient levels of cashmere goats

“…Previous studies showed that the phenotypic traits of ruminants were affected by rumen microbiota, whose functions could be re ected by the ruminal metabolites [23][24][25]. However, most studies have only focused on the single change of dietary protein/energy and few reports studied the comprehensive effects of dietary energy and protein on the rumen bacterial composition and rumen metabolites [3,16,18,22,26,27].…”