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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 ?- or ?-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??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?

SUBMITTER: Moon JY

PROVIDER: S-EPMC6286648 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Moon Jee-Young JY Zolnik Christine P CP Wang Zheng Z Qiu Yunping Y Usyk Mykhaylo M Wang Tao T Kizer Jorge R JR Landay Alan L AL Kurland Irwin J IJ Anastos Kathryn K Kaplan Robert C RC Burk Robert D RD Qi Qibin Q

EBioMedicine 20181023

<h4>Background</h4>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.<h4>Methods</h4>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, bu ...[more]

PMID: 30366816

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Project description:ObjectiveGut dysbiosis and metabolic abnormalities have been implicated in HIV infection. However, the exact causal relationships among the gut microbiota, metabolites, and HIV infection remain poorly understood. Our study involving Mendelian randomization (MR) and mediation analysis aims to unveil these causalities.MethodsGenetic instrumental variables for the gut microbiota were retrieved from MiBioGen consortium (n = 18,340). Metabolism-related genetic variants were sourced from the CLSA cohort (n = 8299). GWAS summary statistics for symptomatic HIV infection were derived from the FinnGen study (n = 309,154), and the UK Biobank (n = 208,808). We performed the bidirectional two-sample MR to assess causalities with the inverse-variance weighted (IVW) method as the primary analysis. Moreover, we executed a mediation analysis using two-step MR methods.ResultsCompared to the causal effects of HIV infection on gut microbiota (or metabolites), those of gut microbiota (or plasma metabolites) on the risk of HIV infection were more substantial. Phylum Proteobacteria (OR: 2.114, 95% CI 1.042-4.288, P = 0.038), and genus Ruminococcaceae UCG013 (OR: 2.127, 95% CI 1.080-4.191, P = 0.029) exhibited an adverse causal effect on HIV infection, whereas genus Clostridium sensu stricto 1(OR: 0.491, 95% CI 0.252-0.956, P = 0.036) and family Erysipelotrichaceae (OR: 0.399, 95% CI 0.193-0.827, P = 0.013) acted as significant protective factors for HIV. The salicyluric glucuronide level (OR = 2.233, 95% CI 1.120-4.453, P = 0.023) exhibited a considerably adverse causal effect on HIV infection. Conversely, the salicylate-to-citrate ratio (OR: 0.417, 95% CI 0.253-0.688, P = 0.001) was identified as a protective factor for HIV. We identified only one bidirectional causality between 1-palmitoyl-GPI and HIV infection. Mechanistically, genus Haemophilus mediated the causal effects of three phospholipids on HIV infection risk: 1-palmitoyl-GPI (mediation proportion = 33.7%, P = 0.018), 1-palmitoyl-2-arachidonoyl-GPI (mediation proportion = 18.3%, P = 0.019), and 1-linoleoyl-2-linolenoyl-GPC (mediation proportion = 20.3%, P = 0.0216). Additionally, 5-Dodecenoylcarnitine (C12:1) mediated the causal effect of genus Sellimonas on the risk of HIV infection (mediation proportion = 13.7%, P = 0.0348).ConclusionOur study revealed that gut microbiota and metabolites causally influence HIV infection risk more substantially than the reverse. We identified the bidirectional causality between 1-palmitoyl-GPI (16:0) and HIV infection, and elucidated four mediation relationships. These findings provide genetic insights into prediction, prevention, and personalized medicine of HIV infection.

Project description:BackgroundAlterations in gut microbiota have been implicated in HIV infection and cardiovascular disease. However, how gut microbial alterations relate to host inflammation and metabolite profiles, and their relationships with atherosclerosis, have not been well-studied, especially in the context of HIV infection. Here, we examined associations of gut microbial species and functional components measured by shotgun metagenomics with carotid artery plaque assessed by B-mode carotid artery ultrasound in 320 women with or at high risk of HIV (65% HIV +) from the Women's Interagency HIV Study. We further integrated plaque-associated microbial features with serum proteomics (74 inflammatory markers measured by the proximity extension assay) and plasma metabolomics (378 metabolites measured by liquid chromatography tandem mass spectrometry) in relation to carotid artery plaque in up to 433 women.ResultsFusobacterium nucleatum, a potentially pathogenic bacteria, was positively associated with carotid artery plaque, while five microbial species (Roseburia hominis, Roseburia inulinivorans, Johnsonella ignava, Odoribacter splanchnicus, Clostridium saccharolyticum) were inversely associated with plaque. Results were consistent between women with and without HIV. Fusobacterium nucleatum was positively associated with several serum proteomic inflammatory markers (e.g., CXCL9), and the other plaque-related species were inversely associated with proteomic inflammatory markers (e.g., CX3CL1). These microbial-associated proteomic inflammatory markers were also positively associated with plaque. Associations between bacterial species (especially Fusobacterium nucleatum) and plaque were attenuated after further adjustment for proteomic inflammatory markers. Plaque-associated species were correlated with several plasma metabolites, including the microbial metabolite imidazole-propionate (ImP), which was positively associated with plaque and several pro-inflammatory markers. Further analysis identified additional bacterial species and bacterial hutH gene (encoding enzyme histidine ammonia-lyase in ImP production) associated with plasma ImP levels. A gut microbiota score based on these ImP-associated species was positively associated with plaque and several pro-inflammatory markers.ConclusionAmong women living with or at risk of HIV, we identified several gut bacterial species and a microbial metabolite ImP associated with carotid artery atherosclerosis, which might be related to host immune activation and inflammation. Video Abstract.

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

Publications

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

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