Tryptophan metabolism, gut microbiota, and carotid artery plaque in women with and without HIV infection.

OBJECTIVE: The perturbation of tryptophan (TRP) metabolism has been linked with HIV infection and cardiovascular disease (CVD), but the interrelationship among TRP metabolites, gut microbiota, and atherosclerosis remain unclear in the context of HIV infection. METHODS: We included 361 women (241 HIV+, 120 HIV-) with carotid artery plaque assessments from the Women's Interagency HIV Study, measured 10 plasma TRP metabolites and profiled fecal gut microbiome. TRP metabolite-related gut bacteria were selected through the Analysis of Compositions of Microbiomes with Bias Correction method. Associations of TRP metabolites and related microbial features with plaque were examined using multivariable logistic regression. RESULTS: Although plasma kynurenic acid (KYNA) [odds ratio (OR) = 1.93, 95% confidence interval (CI): 1.12-3.32 per one SD increase; P  = 0.02) and KYNA/TRP [OR = 1.83 (95% CI 1.08-3.09), P  = 0.02] were positively associated with plaque, indole-3-propionate (IPA) [OR = 0.62 (95% CI 0.40-0.98), P  = 0.03] and IPA/KYNA [OR = 0.51 (95% CI 0.33-0.80), P  < 0.01] were inversely associated with plaque. Five gut bacterial genera and many affiliated species were positively associated with IPA (FDR-q < 0.25), including Roseburia spp ., Eubacterium spp., Lachnospira spp., and Coprobacter spp.; but no bacterial genera were found to be associated with KYNA. Furthermore, an IPA-associated-bacteria score was inversely associated with plaque [OR = 0.47 (95% CI 0.28-0.79), P  < 0.01]. But no significant effect modification by HIV serostatus was observed in these associations. CONCLUSION: In a cohort of women living with and without HIV infection, plasma IPA levels and related gut bacteria were inversely associated with carotid artery plaque, suggesting a potential beneficial role of IPA and its gut bacterial producers in atherosclerosis and CVD.

Gut Microbiota and Cognitive Function Among Women Living with HIV.

BACKGROUND: Altered gut microbiota has been associated with cognitive dysfunction and Alzheimer's disease, but little is known among people living with HIV. OBJECTIVE: To examine associations between gut microbiota and cognitive impairment among women with or without HIV. METHODS: This is a cross-sectional study of 446 women (302 HIV+) who had completed a neuropsychological test battery and stool sample collected within 1 year. Gut microbiota composition was quantified using 16SV4 rRNA gene sequencing and microbial functional pathways were predicted using PICRUSt. Cognitive domains included attention, executive function, learning, memory, fluency, processing speed, and motor function. Cognitive impairment was defined as two or more domains with T scores < 1 SD below mean. ANCOM-II was used to identify taxa and functional pathways associated with cognitive impairment, and the associations were further examined by multivariable logistic regression. RESULTS: In overall sample, adjusting for multiple covariates including HIV status, we found that higher abundance of Methanobrevibacter, Odoribacter, Pyramidobacter, Eubacterium, Ruminococcus, and Gemmiger, and lower abundance of Veillonella were associated with cognitive impairment. The associations between these taxa and cognitive impairment were more profound in HIV+ women compared to HIV- women. Most associations with bacterial taxa were observed for learning and memory. We found accompanying microbial functional differences associated with cognitive impairment, including twelve enriched pathways and three depleted pathways. CONCLUSIONS: In women with or without HIV infection, this study identified multiple altered gut bacterial taxa and functional pathways associated with cognitive impairment, supporting the potential role of gut microbiota in cognitive dysfunction and Alzheimer's disease.

Association of Gut Microbiota With Objective Sleep Measures in Women With and Without Human Immunodeficiency Virus Infection: The IDOze Study.

BACKGROUND: Poor sleep health is an underrecognized health challenge, especially for people with human immunodeficiency virus (HIV). Gut microbiota related to sleep are underinvestigated. METHODS: The IDOze microbiota substudy included 190 women (114 with HIV and 76 without HIV). Wrist actigraphy measured total sleep duration, sleep efficiency, number of wake bouts, wake after sleep onset, fragmentation index, and sleep timing. 16S rRNA gene sequencing identified gut microbial genera. Analysis of compositions of microbiomes with bias correction was used to investigate cross-sectional associations between gut microbiota and sleep. Abundances of sleep-related gut microbial genera were compared between women with and without HIV. RESULTS: Enrichment of 7 short-chain fatty acid-producing genera (eg, Butyricimonas, Roseburia, and Blautia) was associated with lower fragmentation index. Enrichment of 9 genera (eg, Dorea) was associated with lower sleep efficiency and/or more wake after sleep onset. Enrichment of proinflammatory Acidaminococcus was associated with late sleep midpoint and offset time. These associations were largely consistent regardless of HIV status. The abundance of Butyricimonas was lower among women with HIV compared to those without HIV. CONCLUSIONS: Seventeen genera were identified to be associated with sleep continuity or timing. Butyricimonas, a potentially beneficial genus associated with sleep continuity, was less abundant among women with HIV.

Gut microbiota, circulating inflammatory markers and metabolites, and carotid artery atherosclerosis in HIV infection.

BACKGROUND: Alterations 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. RESULTS: Fusobacterium 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. CONCLUSION: Among 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.

Anti-HPV16 Antibody Titers Prior to an Incident Cervical HPV16/31 Infection.

The goal of this study was to investigate the serological titers of circulating antibodies against human papillomavirus (HPV) type 16 (anti-HPV16) prior to the detection of an incident HPV16 or HPV31 infection amongst vaccinated participants. Patients were selected from a prospective post-HPV vaccine longitudinal cohort at Mount Sinai Adolescent Health Center in Manhattan, NY. We performed a nested case-control study of 43 cases with incident detection of cervical HPV16 (n = 26) or HPV31 (n = 17) DNA who had completed the full set of immunizations of the quadrivalent HPV vaccine (4vHPV). Two control individuals whom had received three doses of the vaccine (HPV16/31-negative) were selected per case, matched on age at the first dose of vaccination and follow-up time in the study: a random control, and a high-risk control that was in the upper quartile of a sexual risk behavior score. We conducted an enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G (IgG) antibodies specific to anti-HPV16 virus-like particles (VLPs). The results suggest that the average log antibody titers were higher among high-risk controls than the HPV16/31 incident cases and the randomly selected controls. We show a prospective association between anti-HPV16 VLP titers and the acquisition of an HPV16/31 incident infection post-receiving three doses of 4vHPV vaccine.