Gut dysbiosis of bacteria and fungi associated with human immunodeficiency virus infection.
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ABSTRACT:
SUBMITTER: Wu X
PROVIDER: S-EPMC9433070 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Gut dysbiosis of bacteria and fungi associated with human immunodeficiency virus infection.
Wu Xueqi X Xu Yuanhong Y Li Qingfeng Q Yang Fengjiao F He Shenghua S Li Yingjie Y Yang Shujuan S Zeng Peibin P
Chinese medical journal 20220605 11
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Project description:BackgroundThe status of vaginal microbiota in persistent high-risk human papilloma virus (HR-HPV) infection is unclear. The present work aimed to identify the vaginal microbiota of persistent HPV infection and explore the possible underlying microbiota factors.MethodsA total of 100 women were recruited in this study, of which 28 presented HR-HPV persistent infection (P group), 30 showed clearance of any subtype of HR-HPV (C group), and 42 had no history of any HR-HPV infection (NC group). The vaginal microbiota and the community structure of the three groups were compared based on the 16S rRNA sequencing of the V3-V4 region. The microbiota diversity and differential analysis were carried out to detect the potential factors associated with HR-HPV infection.ResultsP and C groups showed an increase of Firmicutes and Actinobacteriota but a decrease in Proteobacteria compared to the NC group. The Chao1 index indicated that the microbial richness of the NC group was greater than C group (P < 0.05).The principal co-ordinate analysis(PCoA) revealed differences between the NC and P/C groups.The linear discriminant analysis effect size (LEfSe) method indicated that Proteobacteria phylum was significantly different in the mean relative abundance in the NC group,but the P and C groups did not show such indicative taxa. The Wilcox rank-sum test indicated that the Bifidobacterium (P = 0.002) and Lactobacillus (P = 0.005) of the C group were in a high mean relative abundance compared to the NC group.ConclusionsThe persistent HR-HPV infection is associated with dysbiosis of the vaginal microbiota. Microbiome regulation with Bifidobacteria and Lactobacillus may affect the clearance of HPV.
| S-EPMC8722078 | biostudies-literature
Project description:ObjectivesKnee synovitis is a highly prevalent and potentially curable condition for knee pain; however, its pathogenesis remains unclear. We sought to assess the associations of the gut fungal microbiota and the fungi-bacteria correlation network with knee synovitis.MethodsParticipants were derived from a community-based cross-sectional study. We performed an ultrasound examination of both knees. A knee was defined as having synovitis if its synovium was ≥4 mm and/or Power Doppler (PD) signal was within the knee synovium area (PD synovitis). We collected faecal specimens from each participant and assessed gut fungal and bacterial microbiota using internal transcribed spacer 2 and shotgun metagenomic sequencing. We examined the relation of α-diversity, β-diversity, the relative abundance of taxa and the interkingdom correlations to knee synovitis.ResultsAmong 977 participants (mean age: 63.2 years; women: 58.8%), 191 (19.5%) had knee synovitis. β-diversity of the gut fungal microbiota, but not α-diversity, was significantly associated with prevalent knee synovitis. The fungal genus Schizophyllum was inversely correlated with the prevalence and activity (ie, control, synovitis without PD signal and PD synovitis) of knee synovitis. Compared with those without synovitis, the fungi-bacteria correlation network in patients with knee synovitis was smaller (nodes: 93 vs 153; edges: 107 vs 244), and the average number of neighbours was fewer (2.3 vs 3.2).ConclusionAlterations of gut fungal microbiota and the fungi-bacteria correlation network are associated with knee synovitis. These novel findings may help understand the mechanisms of the gut-joint axis in knee synovitis and suggest potential targets for future treatment.
| S-EPMC10749022 | biostudies-literature
Project description:Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-Delta32, CCR2-64I, and SDF-1-3'A) which have been associated with slower disease progression. HIV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HIV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC). Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1- or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino-acid insertion in Vpu. The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases.
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Project description:Mucosa-associated invariant T (MAIT) cells are recently characterized as a novel subset of innate-like T cells that recognize microbial metabolites as presented by the MHC-1b-related protein MR1. The significance of MAIT cells in anti-bacterial defense is well-understood but not clear in viral infections such as SIV/HIV infection. Here we studied the phenotype, distribution, and function of MAIT cells and their association with plasma viral levels during chronic SHIV infection in rhesus macaques (RM). Two groups of healthy and chronic SHIV-infected macaques were characterized for MAIT cells in blood and mucosal tissues. Similar to human, we found a significant fraction of macaque T cells co-expressing MAIT cell markers CD161 and TCRVα-7.2 that correlated directly with macaque MR1 tetramer. These cells displayed memory phenotype and expressed high levels of IL-18R, CCR6, CD28, and CD95. During chronic infection, the frequency of MAIT cells are enriched in the blood but unaltered in the rectum; both blood and rectal MAIT cells displayed higher proliferative and cytotoxic phenotype post-SHIV infection. The frequency of MAIT cells in blood and rectum correlated inversely with plasma viral RNA levels and correlated directly with total CD4 T cells. MAIT cells respond to microbial products during chronic SHIV infection and correlated positively with serum immunoreactivity to flagellin levels. Tissue distribution analysis of MAIT cells during chronic infection showed significant enrichment in the non-lymphoid tissues (lung, rectum, and liver) compared to lymphoid tissues (spleen and LN), with higher levels of tissue-resident markers CD69 and CD103. Exogenous in vitro cytokine treatments during chronic SHIV infection revealed that IL-7 is important for the proliferation of MAIT cells, but IL-12 and IL-18 are important for their cytolytic function. Overall our results demonstrated that MAIT cells are enriched in blood but unaltered in the rectum during chronic SHIV infection, which displayed proliferative and functional phenotype that inversely correlated with SHIV plasma viral RNA levels. Treatment such as combined cytokine treatments could be beneficial for enhancing functional MAIT cells during chronic HIV infection in vivo.
| S-EPMC6978843 | biostudies-literature
Project description:ObjectivesThis study sought to investigate outcomes of heart failure (HF) in veterans living with human immunodeficiency virus (HIV).BackgroundData on outcomes of HF among people living with human immunodeficiency virus (PLHIV) are limited.MethodsWe performed a retrospective cohort study of Veterans Health Affairs data to investigate outcomes of HF in PLHIV. We identified 5,747 HIV+ veterans with diagnosis of HF from 2000 to 2018 and 33,497 HIV- frequency-matched controls were included. Clinical outcomes included all-cause mortality, HF hospital admission, and all-cause hospital admission.ResultsCompared with HIV- veterans with HF, HIV+ veterans with HF were more likely to be black (56% vs. 14%), be smokers (52% vs. 29%), use alcohol (32% vs. 13%) or drugs (37% vs. 8%), and have a higher comorbidity burden (Elixhauser comorbidity index 5.1 vs. 2.6). The mean ejection fraction (EF) (45 ± 16%) was comparable between HIV+ and HIV- veterans. HIV+ veterans with HF had a higher age-, sex-, and race-adjusted 1-year all-cause mortality (30.7% vs. 20.3%), HF hospital admission (21.2% vs. 18.0%), and all-cause admission (50.2% vs. 38.5%) rates. Among veterans with HIV and HF, those with low CD4 count (<200 cells/ml) and high HIV viral load (>75 copies/μl) had worse outcomes. The associations remained statistically significant after adjusting for extensive list of covariates. The incidence of all-cause mortality and HF admissions was higher among HIV+ veterans with ejection fraction <45% CONCLUSIONS: HIV+ veterans with HF had higher risk of hospitalization and mortality compared with their HIV- counterparts, with worse outcomes reported for individuals with lower CD4 count, higher viral load, and lower ejection fraction.
| S-EPMC9019736 | biostudies-literature
Project description:BackgroundInflammation persists among persons with human immunodeficiency virus (PWH) despite effective antiretroviral therapy and may contribute to T-cell dysfunction. Alcohol use is prevalent among PWH and promotes intestinal leak, dysbiosis, and a proinflammatory milieu. Whether alcohol use is associated with T-cell late differentiation remains to be investigated.MethodsData and samples from PWH (N = 359 of 365) enrolled in the New Orleans Alcohol Use in HIV Study were used. Alcohol use was assessed by self-report (Alcohol Use Disorders Identification Test; lifetime alcohol exposure; 30-day Alcohol Timeline Followback) and phosphatidylethanol (PEth) quantitation. In a subset of participants, fecal bacterial content was assessed by ribosomal 16S marker gene deep sequencing and quantitative polymerase chain reaction. Intestinal leak was assessed by fecal-to-plasma α-1-antitrypsin (A1AT) enzyme-linked immunosorbent assay ratio. Peripheral T-cell populations were quantified by flow cytometry.ResultsAlcohol Use Disorder Identification Test scores were positively associated with activated-senescent, exhausted, and terminal effector memory CD45RA+CD8+ but not CD4+ T cells (cells/μL) after confounder adjustment (P < .050). Phosphatidylethanol was positively associated with A1AT (P < .050). The PEth and activated-senescent CD8+ were associated with bacterial β-diversity (P < .050) and positively associated with the relative abundance of coabundant Prevotellaceae members (q < .100).ConclusionsAlcohol use among PWH is associated with CD8+ T-cell late differentiation, intestinal leak, and dysbiosis. Alcohol-associated dysbiosis is implicated in CD8+ T-cell senescence.
| S-EPMC8006423 | biostudies-literature
Project description:Human immunodeficiency virus (HIV) infection is characterized by a massive loss of CD4 T cells in the gastrointestinal tract (GIT) that is accompanied by changes in the gut microbiome and microbial translocation that contribute to inflammation and chronic immune activation. Though highly active antiretroviral therapy (HAART) has led to better long-term outcomes in HIV infected patients, it has not been as effective at reverting pathogenesis in the GIT. Using the simian immunodeficiency virus (SIV) infection model, we show that combination antiretroviral therapy (c-ART) partially reverted microbial dysbiosis observed during SIV infection. Though the relative abundance of bacteria, their richness or diversity did not significantly differ between infected and treated animals, microbial dysbiosis was evident via multiple beta diversity metrics: Jaccard similarity coefficient, Bray-Curtis similarity coefficient, and Yue & Clayton theta similarity coefficient. Principal coordinates analysis (PCoA) clustered SIV-infected untreated animals away from healthy and treated animals that were clustered closely, indicating that c-ART partially reversed the gut dysbiosis associated with SIV infection. Metastats analysis identified specific operational taxonomic units (OTUs) falling within the Streptococcus, Prevotella, Acinetobacter, Treponema, and Lactobacillus genera that were differentially represented across the three groups. Our results suggest that complete viral suppression with c-ART could potentially revert microbial dysbiosis observed during SIV and HIV infections.
| S-EPMC7156522 | biostudies-literature
Project description:Herpes simplex virus 1 (HSV) is a ubiquitous human virus resident in a majority of the global population as a latent infection. Acyclovir (ACV), is the standard of care drug used to treat primary and recurrent infections, supplemented in some patients with intravenous immunoglobulin (IVIG) treatment to suppress infection and deleterious inflammatory responses. As many diverse medications have recently been shown to change composition of the gut microbiome, we used Illumina 16S rRNA gene sequencing to determine the effects of ACV and IVIG on the gut bacterial community. We found that HSV, ACV and IVIG can all independently disrupt the gut bacterial community in a sex biased manner when given to uninfected C57BL/6 mice. Treatment of HSV infected mice with ACV or IVIG alone or together revealed complex interactions between these drugs and infection that caused pronounced sex biased dysbiosis. ACV reduced Bacteroidetes levels in male but not female mice, while levels of the Anti-inflammatory Clostridia (AIC) were reduced in female but not male mice, which is significant as these taxa are associated with protection against the development of graft versus host disease (GVHD) in hematopoietic stem cell transplant (HSCT) patients. Gut barrier dysfunction is associated with GVHD in HSCT patients and ACV also decreased Akkermansia muciniphila, which is important for maintaining gut barrier functionality. Cumulatively, our data suggest that long-term prophylactic ACV treatment of HSCT patients may contribute to GVHD and also potentially impact immune reconstitution. These data have important implications for other clinical settings, including HSV eye disease and genital infections, where ACV is given long-term.
| S-EPMC7410316 | biostudies-literature
Project description:The biological mechanisms underlying emotional distress in HIV infection are likely to be complex but remain understudied. We investigated whether dysbiotic signatures in the gut microbiome of persons living with HIV (PLWH) are associated with their emotional status. We retrospectively examined the gut microbiome and clinical evaluation of 129 adults (94 PLWH and 35 HIV-) enrolled at UC San Diego's HIV Neurobehavioral Research Program. A subset of participants (32 PLWH vs. 13 HIV-) underwent an emotional assessment using the NIH Toolbox Emotion Battery summarized by three composite scores (negative affect, social satisfaction, and psychological well-being). We then sequenced the 16S rDNA V3-V4 regions from stool and performed taxonomic assignment using CLC Microbial Genomics Module. The gut microbiota profiles were evaluated in relation to participants' emotional assessment. All analyses were done in R statistical software. We found that the relative abundance of aerotolerant bacteria was significantly higher in PLWH (p < 0.01) and was associated with a lifetime major depression diagnosis independently of HIV status (p = 0.05). Moreover, PLWH experienced significantly worse psychological well-being (p = 0.02), less social satisfaction (p = 0.03), and more negative affect (p = 0.02). Higher levels of aerotolerant bacteria were associated with worse psychological well-being (rho = -0.35, p = 0.02), less social satisfaction (r = - 0.42, p < 0.01), and more negative affect (rho = 0.46, p < 0.01). The association of aerotolerant bacteria with social satisfaction and negative affect was independent of HIV status (p < 0.05, for both). The over-representation of aerotolerant bacteria in the gut may reflect worse oxidative stress and barrier defects and may contribute to emotional distress during HIV infection.
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