Circulating levels of the anti-oxidant indoleproprionic acid are associated with higher gut microbiome diversity

Abstract

The gut microbiome has recently emerged as an important regulator of insulin resistance and abdominal obesity. The tryptophan metabolite generated by the gut microbiome, indoleproprionic acid (IPA) has been shown to predict the onset of type 2 diabetes. IPA is a metabolite produced by gut microbes from dietary tryptophan that exhibits a high degree of inter-individual variation. The microbiome composition parameters that are associated with circulating levels of this potent anti-oxidant have however not been investigated to date in human populations. In 1018 middle-aged women from the TwinsUK cohort, we assessed the relationship between serum IPA levels and gut microbiome composition targeting the 16S rRNA gene. Microbiome alpha-diversity was positively correlated with serum indoleproprionic acid levels (Shannon Diversity: Beta[95%CI] = 0.19[0.13;0.25], P = 6.41 × 10−10) after adjustment for covariates. Sixteen taxa and 12 operational taxonomic units (OTUs) associated with IPA serum levels. Among these are positive correlations with the butyrate-producing Faecalibacterium prausnitzii, the class Mollicutes and the order RF39 of the Tenericutes, and Coprococcus Negative correlations instead were observed with Eubacterium dolichum previously shown to correlate with visceral fat mass and several genera in the Lachnospiraceae family such as Blautia and Ruminococcus previously shown to correlate with obesity. Microbiome composition parameters explained ~20% of the variation in circulating levels of IPA, whereas nutritional and host genetic parameters explained only ~4%. Our data confirm an association between IPA circulating levels and metabolic syndrome parameters and indicate that gut microbiome composition influences IPA levels.

Lower gut microbiome diversity and higher abundance of proinflammatory genus Collinsella are associated with biopsy-proven nonalcoholic steatohepatitis

“…Members of the Mollicutes class have previously been linked to obesity 36 , but their functional roles are unclear. 37 Recent work 38 has correlated abundance of Mollicutes RF39 with circulating indolepropionic acid, a potent antioxidant produced by the microbiota and associated with a lower risk of type II diabetes 39,40 thus providing a likely mechanism protective for NAFLD.…”

The Controversial Role of Human Gut Lachnospiraceae

“…IS and pCS are the products of tryptophan and tyrosine metabolism by the gut bacteria, and their increase following vancomycin therapy in ESRD patients indicates the resilience of the taxa generating these toxins [57]. Within a cohort of 1018 middle-aged women from TwinsUK, Blautia was the most common taxon associated with lower levels of indole-propionic acid (IPA), whereas a positive correlation was observed between IPA and Coprococcus [58]. IPA is a deamination product of tryptophan metabolism that has an important effect on host gut barrier function and antioxidant activity [20].…”

Serum metabolites reflecting gut microbiome alpha diversity predict type 2 diabetes

“…24 It regulates gastrointestinal barrier function via its interaction with the pregnane X receptor (PXR), which is predictive of the onset of type 2 diabetes, 16 has been shown to be strongly correlated with higher gut microbiome diversity and its levels in serum are determined primarily by gut microbiome composition. 25 Among the compounds that intestinal bacteria can metabolize there are sterols, bile acids, and steroid hormones. 26 The metabolites generated by gut bacteria action on host steroids, when reabsorbed in the intestine back into the circulation, produce biological effects.…”

“…Visceral fat (VF), BMI, obesity and Homa2-IR were measured as previously described. 25 Incident T2D cases were defined with the same criteria but having developed T2D at follow-up (mean (SD) = 8.16 (1.3) y).…”