Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites

Abstract

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. Here, we report a broad MS-based metabolomics study that demonstrates a surprisingly large effect of the gut ''microbiome'' on mammalian blood metabolites. Plasma extracts from germ-free mice were compared with samples from conventional (conv) animals by using various MS-based methods. Hundreds of features were detected in only 1 sample set, with the majority of these being unique to the conv animals, whereas Ϸ10% of all features observed in both sample sets showed significant changes in their relative signal intensity. Amino acid metabolites were particularly affected. 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. 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. Multiple organic acids containing phenyl groups were also greatly increased in the presence of gut microbes. 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. Together, these results suggest a significant interplay between bacterial and mammalian metabolism.

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

“…Some of the indole metabolites (such as indole lactate, indole propionate, indole‐3‐aldehyde and indole) produced by the action of various gut commensals on Trp are ligands or precursors of ligands of the AHR. Several of these metabolites are predominantly or exclusively produced by the gut microbiota and circulating levels are determined by the composition of the gut microbiota 35. Activation of AHR on astrocytes and microglia controls microglial activation, modulates the transcriptional program of astrocytes14 and dampens neuroinflammation.…”

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…[72][73][74][75] To this end, GF animals exhibit striking alterations in circulating tryptophan levels and serotonergic neurotransmission, at least in the hippocampus. [10,76] Similarly, alterations in the microbiota in a murine model of autism are associated with deficient tryptophan metabolism and gastrointestinal dysfunction. [77] Prebiotic and probiotic treatments have been shown to alter central levels of serotonin or serotonin receptors in the hippocampus and prefrontal cortex, both regions that are highly connected to the amygdala.…”

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

“…metagenomic (i.e., gut microbiota) effects and environmental factors. Indeed, both system-wide (i.e., whole organism) and organ-specific changes in biochemical processes have components driven by these factors (Martin et al 2009a, b;Nicholson et al 2005;Claus et al 2011;Mestdagh et al 2011;Merrifield et al 2011;Wikoff et al 2009).…”