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. 2025 Sep 1;39(11):1580-1591.
doi: 10.1097/QAD.0000000000004231. Epub 2025 May 5.

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

Chengyong Jia  1 , Brandilyn A Peters  1 , Mykhaylo Usyk  1 , Zheng Wang  1 , David B Hanna  1 , Anjali Sharma  2 , Kathryn Anastos  1   2 , Robert C Kaplan  1   3 , Robert D Burk  1   4 , Qibin Qi  1
Affiliations

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

Chengyong Jia et al. AIDS. .

Abstract

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.

Keywords: HIV; fecal metabolite; gut microbiota; plasma metabolite; type 2 diabetes.

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Conflict of interest statement

Competing interests

The authors declare no competing interests.

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