Indole derivatives and their associated microbial genera are associated with the 1-year changes in cardiometabolic risk markers in Chinese adults

Background: Although emerging evidence suggests that indole derivatives, microbial metabolites of tryptophan, may improve cardiometabolic health, the effective metabolites remain unclear. Also, the gut microbiota that involved in producing indole derivatives are less studied. We identified microbial taxa that can predict serum concentrations of the key indole metabolite indole-3-propionic acid (IPA) at population level and investigated the associations of indole derivatives and IPA-predicting microbial genera with cardiometabolic risk markers.

Methods: In a cohort of 318 community-dwelling adults, serum indole metabolites and fecal microbiota (16S ribosomal RNA) were measured at baseline. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose were repeatedly measured at baseline and again after 1 year. Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were measured after 1 year. The association between indole derivatives and the 1-year changes in blood lipids and glucose, and association of indole derivatives with baPWV and ABI were investigated using linear regression models.

Results: Each 1 µmol/L increase in indole-3-acetic acid (IAA) levels was associated with 5.08% (P = 0.046) decrease in LDL-C. IPA levels were inversely associated with baPWV (percentage difference = -1.32%, P = 0.036). Per 1 µmol/L increase in Indole-3-aldehyde (IAld) levels was associated with 1.91% (P = 0.004) decrease in TC and 0.58% (P = 0.019) increase in ABI, but 1.79% decrease in HDL-C with borderline significance (P = 0.050). We identified 18 bacterial genera whose relative abundance was positively associated with serum IPA concentrations (P_FDR < 0.05) and constructed a microbial score to reflect the overall IPA-producing potential. This score was inversely associated with baPWV (percentage difference = -0.48%, P = 0.007).

Conclusions: Our results suggest that IAA, IPA, IAld, and IPA-predicting microbial score are favorably associated with several cardiometabolic risk markers, although IAld may decrease HDL-C levels.