For example, genes for specific metabolic pathways such as amino acid and glycan metabolism were found to be overrepresented in the microbiome of the distal gut, reinforcing the notion that human metabolism is an amalgamation of microbial and human attributes ( 13).
More recently, metagenomic techniques have been used to characterize both the composition and the potential physiological effects of entire microbial communities without having to culture individual community members. Historically, classical microbiology methods including the isolation and culture of individual bacterial species associated with the gut were used to study microbial colonization of higher organisms. Differences in commensal microflora are likely to impact human health and disease through any number of ways reflective of the complex nature of the microbiome itself. Alternatively, probiotic therapy is the attempt to alter the extant gut microbial environment through the ingestion of live consumable cultures of beneficial bacteria ( 12). The composition of the gut microbiome is highly variable ( 9), and its diversity can be significantly affected by alterations in diet ( 2, 10) or antibiotic use ( 11). Normal host activities, including the processing of nutrients and the regulation of the immune system, are affected by the intestinal microbiome ( 2, 3), and the microbiome has been implicated in the pathogenesis of diseases such as nonalcoholic steatohepatitis ( 4), allergy ( 5), the formation of gallstones ( 6), and inflammatory bowel disease ( 7, 8). The combined genetic potential of the endogenous flora is referred to as the “microbiome” ( 1), and typically results in a mutualistic relationship between microbe and host. The human body is colonized by hundreds of trillions of microbes, which collectively possess hundreds of times as many genes as coded in the human genome. Together, these results suggest a significant interplay between bacterial and mammalian metabolism. A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was observed, suggesting that the gut microflora has a direct impact on the drug metabolism capacity of the host. Multiple organic acids containing phenyl groups were also greatly increased in the presence of gut microbes. Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. For example, the bacterial-mediated production of bioactive indole-containing metabolites derived from tryptophan such as indoxyl sulfate and the antioxidant indole-3-propionic acid (IPA) was impacted. Amino acid metabolites were particularly affected. Hundreds of features were detected in only 1 sample set, with the majority of these being unique to the conv animals, whereas ≈10% of all features observed in both sample sets showed significant changes in their relative signal intensity. Plasma extracts from germ-free mice were compared with samples from conventional (conv) animals by using various MS-based methods.
Here, we report a broad MS-based metabolomics study that demonstrates a surprisingly large effect of the gut “microbiome” on mammalian blood metabolites. Although it has long been recognized that the enteric community of bacteria that inhabit the human distal intestinal track broadly impacts human health, the biochemical details that underlie these effects remain largely undefined.