Gut microbiota and plasma metabolites associated with diabetes in women with, or at high risk for, HIV infection

Abstract

Background: Gut microbiota alteration has been implicated in HIV infection and metabolic disorders. The relationship between gut microbiota and diabetes has rarely been studied in HIV-infected individuals, who have excess risk of metabolic disorders.

Methods: Our study during 2015-2016 enrolled predominantly African Americans and Hispanics in the Women's Interagency HIV Study. We studied 28 women with long-standing HIV infection under antiretroviral therapy and 20 HIV-uninfected, but at high risk of infection, women (16 HIV+ and 6 HIV- with diabetes). Fecal samples were analyzed by sequencing prokaryotic16S rRNA gene. Plasma metabolomics profiling was performed by liquid chromatography-tandem mass spectrometry.

Findings: No significant differences in bacterial α- or β-diversity were observed by diabetes or HIV serostatus (all P > .1). Relative abundances of four genera (Finegoldia, Anaerococcus, Sneathia, and Adlercreutzia) were lower in women with diabetes compared to those without diabetes (all P < .01). In women with diabetes, plasma levels of several metabolites in tryptophan catabolism (e,g., kynurenine/tryptophan ratio), branched-chain amino acid and proline metabolism pathways were higher, while glycerophospholipids were lower (all P < .05). Results were generally consistent between HIV-infected and HIV-uninfected women, and no significant modification effects by HIV serostatus were observed (all P_interaction > 0.05). Anaerococcus, known to produce butyrate which is involved in anti-inflammation and glucose metabolism, showed an inverse correlation with kynurenine/tryptophan ratio (r = -0.38, P < .01).

Interpretation: Among women with or at high risk for HIV infection, diabetes is associated with gut microbiota and plasma metabolite alteration, including depletion of butyrate-producing bacterial population along with higher tryptophan catabolism. FUND: NHLBI (K01HL129892, R01HL140976) and FMF.

Keywords: Diabetes; Gut microbiota; HIV; Metabolite.

Fig. 1

Microbial composition and diversity by HIV serostatus and diabetes (a) Principal coordinates analysis of Bray-Curtis dissimilarity of microbiota by HIV serostatus and diabetes, (b) Alpha diversity of microbiota by HIV serostatus and diabetes. Observed richness is in the OTU level, and Chao 1 and Shannon index are in the genus level. A bar represents a median of the group.

Fig. 2

Relative abundance of four bacterial genera by diabetes status. A bar represents the mean relative abundances and an error bar represents 1 standard error of relative abundances. The topmost P-value is the significance level of differential abundances between the women with diabetes and without diabetes, tested by a linear regression adjusting for age and HIV serostatus, and P-values in the second line are the significance levels of differential abundances between the women with diabetes and without diabetes, tested by linear regressions adjusting for age among HIV+ (left) and among HIV- (right).

Fig. 3

Metabolic concentration levels by diabetes status. A bar represents the mean concentrations (ratio for kynurenine/tryptophan ratio) and an error bar represents 1 standard error of concentrations (ratio for kynurenine/tryptophan ratio). The topmost P-value is the significance level of differential concentrations between the women with diabetes and without diabetes [Mann-Whitney U test], and P-values in the second line are the significance levels of differential concentrations between the women with diabetes and without diabetes [Mann-Whitney U test], among HIV+ (left) and among HIV- (right). All P for interaction of diabetes status and HIV serostatus >.18 [linear regression].