Associations of fecal and blood microbiota-related metabolites with gut microbiota and type 2 diabetes in HIV infection

Objectives: Assess the relationships of gut microbiota (GMB)-related metabolites in feces and blood with GMB and type 2 diabetes (T2D) in the context of HIV infection, the presence of which could disrupt host metabolism. Design: We conducted a cross-sectional study among 111 women with HIV (WWH) and 56 women without HIV (WWOH) in the MACS/WIHS Combined Cohort Study. Methods: We measured 62 targeted metabolites in both feces and plasma and examined their associations with GMB composition (243 species) and prevalent T2D. Results: We observed 44 metabolites with detection rates ≥25% in both feces and plasma. Correlations between fecal and plasma metabolites were stronger in WWOH than in WWH (median r: 0.13 vs. 0.04). Fecal metabolites showed stronger correlations with GMB than plasma metabolites among all participants (median r [IQR] of measured vs. GMB-predicted metabolites: 0.24 [0.11, 0.33] vs. 0.08 [-0.03, 0.24]; P=0.002), and the difference in this comparison was more pronounced in WWOH compared to WWH. We found a moderate consistency for the associations of fecal and plasma metabolites with T2D in WWH (r for effect sizes of fecal and plasma metabolites on T2D=0.36; P=0.03), but not in WWOH (r=0.13; P=0.45). Fecal and plasma kynurenate, a tryptophan catabolism metabolite, showed opposite associations with T2D, with a positive association for plasma (odds ratio (OR): 2.54, 95% confidence interval (CI): [1.28-5.76]; P=0.01) and an inverse association for feces (0.59 [0.27-1.23]; P=0.18) in WWH. Conclusions: Fecal metabolites are more strongly associated with GMB than plasma metabolites, especially among WWOH. HIV infection might also influence associations of fecal and plasma metabolites with T2D.