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.