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The intestinal microbiota is highly metabolically active and plays an important role in many metabolic processes absent from the human host. Altered microbiota metabolism has been linked to diseases such as obesity, cardiovascular disease, and colorectal cancer. However, there is a gap in the current knowledge on how the microbiota interact with its host in terms of metabolic interactions. Here, we performed an integrated analysis between the mucosa-associated microbiota and the mucosa metabolome in healthy, nonhuman primates to investigate these relationships. The microbiota composition was distinct at each tissue location, with variation by host individual also observed. Microbiota-metabolome dynamics were primarily driven by interactions in the distal colon. These interactions were strongly correlated with dietary component, indicating a possibility to modulate microbiota-metabolomic interactions using prebiotic strategies. IMPORTANCE In a healthy colon, the microbiota produces a vast amount of metabolites that are essential to maintaining homeostasis in the colon microenvironment. In fact, these metabolites produced by the microbiota have been linked to diseases such as obesity, cardiovascular disease, and colorectal cancer. In this study, we used healthy nonhuman primate models to investigate the relationship between microbiota and tissue metabolites. We found that both microbiota and metabolites have location-specific signatures along the intestine. Most importantly, we found that metabolites from food sources correlate with multiple bacteria in different intestinal locations. Overall, this work presents a systems-level map of the association between the microbiota and the metabolites in healthy nonhuman primates, provides candidates for experimental validation, and suggests a possibility to regulate the gut microbiota through specific prebiotic combinations.

Mucosal Microbiota and Metabolome along the Intestinal Tract Reveal a Location-Specific Relationship