Signature changes in gut microbiome are associated with increased susceptibility to HIV-1 infection in MSM

Microbiome, Journal Year: 2021, Volume and Issue: 9(1)

Published: Dec. 9, 2021

Abstract Background Men who have sex with men (MSM) been disproportionately affected by HIV-1 since the beginning of AIDS pandemic, particularly in USA and Europe. Compared to women (MSW), MSM a distinct fecal microbiome regardless infection. However, it is unclear whether MSM-associated gut affects susceptibility progression We studied profiles, short-chain fatty acids, blood plasma inflammatory cytokines 109 seroconverters (SC) from early, 1984–1985 phase pandemic Multicenter Cohort Study (MACS) before after infection compared 156 HIV-1-negative MACS (negative controls [NC]). Results found that family Succinivibrionaceae , S24-7, Mogibacteriaceae, Coriobacteriaceae Erysipelotrichaceae were significantly higher ( p <0.05), whereas Odoribacteraceae Verucomicrobiaceae Bacteroidaceae Barnesiellaceae Rikenellaceae lower SC NC. At species level, Prevotella stercorea Eubacterium biforme Collinsella aerofaciens dolichum, Desulfovibrio D168, Alistipes onderdonkii, Ruminococcus torques Bacteroides fragilis, caccae, putredinis Akkermansia muciniphila uniformis ovatus <0.05) After infection, Prevotellaceae Victivallaceae fragilis cylindroides developed within 5 years free for more than 10 without antiretroviral therapy (ART). In addition, Coprococcus eutactus Butyrivibrio crossotus Gemmiger formicilis Blautia obeum 5–10 AIDS-free ART. Furthermore, cytokine levels sCD14, sCD163, interleukin 6, lipopolysaccharide binding protein <0.05 Conclusions Our results suggest pathogenic changes present several months prior early USA. This was associated increased biomarkers risk development AIDS.

Language: Английский

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Relevance of biomarkers indicating gut damage and microbial translocation in people living with HIV

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 21, 2023

The intestinal barrier has the daunting task of allowing nutrient absorption while limiting entry microbial products into systemic circulation. HIV infection disrupts and increases permeability, leading to product translocation. Convergent evidence shown that gut damage an enhanced level translocation contribute immune activation, risk non-AIDS comorbidity, mortality in people living with (PLWH). Gut biopsy procedures are invasive, not appropriate or feasible large populations, even though they gold standard for investigation. Thus, validated biomarkers measure degree needed PLWH. Hematological represent objective indication specific medical conditions and/or their severity, should be able measured accurately reproducibly via easily available standardized blood tests. Several plasma damage, i.e., fatty acid-binding protein (I-FABP), zonulin, regenerating islet-derived protein-3α (REG3α), translocation, such as lipopolysaccharide (LPS) (1,3)-β-D-Glucan (BDG) have been used markers developing comorbidities cross sectional analyses clinical trials, including those aiming at repair damage. In this review, we critically discuss value different estimation permeability levels, paving way towards diagnostic therapeutic strategies epithelial improve overall disease outcomes

Language: Английский

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Gut Bacterial Communities in HIV-Infected Individuals with Metabolic Syndrome: Effects of the Therapy with Integrase Strand Transfer Inhibitor-Based and Protease Inhibitor-Based Regimens

Microorganisms, Journal Year: 2023, Volume and Issue: 11(4), P. 951 - 951

Published: April 6, 2023

Antiretroviral therapies (ART) are strongly associated with weight gain and metabolic syndrome (MetS) development in HIV-infected patients. Few studies have evaluated the association between gut microbiota integrase strand transfer inhibitor (INSTI)-based protease (PI)-based regimens patients MetS. To assess this, fecal samples were obtained from treated different (16 PI + MetS or 30 INSTI MetS) 18 healthy controls (HCs). The microbial composition was characterized using 16S rRNA amplicon sequencing. INSTI-based PI-based a significant decrease α-diversity compared to HCs. group showed lowest both regimens. A increase abundance of short-chain fatty acid (SCFA)-producing genera (Roseburia, Dorea, Ruminococcus torques, Coprococcus) observed group, while Prevotella, Fusobacterium, Succinivibrio significantly increased group. Moreover, Proteobacteria/Firmicutes ratio overrepresented, functional pathways related biosynthesis LPS components receiving INSTIs more pronounced dysbiosis orchestrated by decreased bacterial richness diversity, an almost complete absence SCFA-producing bacteria alterations pathways. These findings not been previously observed.

Language: Английский

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From dysbiosis to defense: harnessing the gut microbiome in HIV/SIV therapy

Microbiome, Journal Year: 2024, Volume and Issue: 12(1)

Published: June 21, 2024

Abstract Background Although the microbiota has been extensively associated with HIV pathogenesis, majority of studies, particularly those using omics techniques, are largely correlative and serve primarily as a basis for hypothesis generation. Furthermore, most have focused on characterizing taxonomic composition bacterial component, often overlooking other levels microbiome. The intricate mechanisms by which influences immune responses to still poorly understood. Interventional studies gut provide powerful tool test whether we can harness improve health outcomes in people HIV. Results Here, review multifaceted role microbiome HIV/SIV disease progression its potential therapeutic target. We explore complex interplay between microbial dysbiosis systemic inflammation, highlighting microbiome-based therapeutics open new avenues management. These include exploring efficacy probiotics, prebiotics, fecal transplantation, targeted dietary modifications. also address challenges inherent this research area, such difficulty inducing long-lasting alterations complexities study designs, including variations probiotic strains, donor selection FMT, antibiotic conditioning regimens, hurdles translating findings into clinical practice. Finally, speculate future directions rapidly evolving field, emphasizing need more granular understanding microbiome-immune interactions, development personalized therapies, application novel technologies identify agents. Conclusions Our underscores importance target innovative strategies.

Language: Английский

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Integrase Inhibitors Partially Restore Bacterial Translocation, Inflammation and Gut Permeability Induced by HIV Infection: Impact on Gut Microbiota

Infectious Diseases and Therapy, Journal Year: 2022, Volume and Issue: 11(4), P. 1541 - 1557

Published: May 26, 2022

Human immunodeficiency virus (HIV) infection can be considered a chronic disease thanks to the extended use of antiretroviral treatment (ART). In this context, low-grade inflammation related gut microbiota (GM) dysbiosis and bacterial translocation (BT) among other factors has been observed despite ART. addition, different ART regimens have demonstrated differential impacts on GM. However, role novel integrase strand transfer inhibitors (INSTIs) not investigated yet. The aim study was analyse effects INSTIs in first-line markers BT, inflammation, cardiovascular risk, permeability GM composition derived short-chain fatty acids.Twenty-six non-HIV-infected volunteers 30 HIV-infected patients (15 naïve 15 under regimen) were recruited. Blood samples extracted biochemical parameters metabolism. analysed using 16S rRNA gene sequencing.Our results showed that HIV increased risk permeability, whereas counteracted these effects. Regarding GM, reduction richness induced by restored INSTIs. Beta diversity revealed people separated from control group independently treatment.Current based are able reverse impact systemic diversity/richness, reaching similar levels those an uninfected/control population. These suggest protective progression, subsequent immune activation development future age-related complications such as events.

Language: Английский

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The Gut and the Translocated Microbiomes in HIV Infection: Current Concepts and Future Avenues

Pathogens and Immunity, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 24, 2024

It is widely acknowledged that HIV infection results in disruption of the gut’s mucosal integrity partly due a profound loss gastrointestinal CD4+ T cells are targets virus. In addition, systemic inflammation and immune activation drive disease pathogenesis reduced but not normalized by antiretroviral therapy (ART). has long been postulated through process microbial translocation, gut microbiome acts as key driver recovery infection. As such, many studies have aimed at characterizing microbiota order to unravel its influence people with reported an association between various bacterial taxa inflammation. This review assesses both contradictory consistent findings among several clarify overall mechanisms which adults may Independently microbiome, observations made from analysis products blood provide direct insight into how translocated recovery. To help better understand strengths limitations reported, this also highlights numerous factors can studies, be they experimental methodologies, host-intrinsic or host-extrinsic factors. Altogether, fuller understanding interplay immunity contribute preventive therapeutic approaches.

Language: Английский

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The intestinal interferon system and specialized enterocytes as putative drivers of HIV latency

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 14, 2025

The barrier to HIV cure is the reservoir, which composed of latently infected CD4 + T cells and myeloid that carry stably integrated replication-competent provirus. gastrointestinal tract (GIT) contains a substantial part reservoir its immunophysiology could be especially conducive for persistence reactivation. However, exact cellular microenvironment molecular mechanisms govern renewal provirus-harboring proviral reactivation in GIT remain unclear. In this review, we outline evidence supporting an overarching hypothesis interferon activity driven by specialized enterocytes creates fosters proliferation sporadic from these cells. First, describe unique immunologic features associated lymphoid tissue (GALT), specifically highlighting IFN potential interactions between neighboring susceptible Then, will dysregulation signaling infection how GALT may contribute latent reservoir. Finally, speculate on clinical implications strategies next steps.

Language: Английский

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Effects of viremia and CD4 recovery on gut “microbiome-immunity” axis in treatment-naïve HIV-1-infected patients undergoing antiretroviral therapy

World Journal of Gastroenterology, Journal Year: 2022, Volume and Issue: 28(6), P. 635 - 652

Published: Feb. 7, 2022

Human immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent systemic inflammation and immune activation, even in patients receiving effective antiretroviral therapy (ART). Converging data from many cross-sectional studies suggest that gut microbiota (GM) changes can occur throughout including human (HIV) infection, treated ART; however, the results are contrasting. For first time, we compared fecal microbial composition, serum metabolites, cytokine profile of treatment-naïve before starting ART after reaching virological suppression, 24 wk therapy. In addition, with CD4/CD8 ratio < (immunological non-responders [INRs]) > responders [IRs]), therapy.To compare for time suppression (HIV RNA 50 copies/mL) ART.We enrolled 12 HIV-infected (mainly based on integrase inhibitors). Fecal composition was assessed through next generation sequencing. a comprehensive analysis blood broad-spectrum panel performed multiplex approach. At same free fatty acid (FFA) short chain levels were obtained gas chromatography-mass spectrometry.We signatures, FFA levels, suppression. Modest alterations observed particular viral condition, detected an increase Ruminococcus Succinivibrio decrease Intestinibacter. Moreover, also augmented propionic butyric acids. Contemporarily, reduction IP-10 IL-8 condition. components between IRs INRs. Concerning microflora population, Faecalibacterium Alistipes Simultaneously, isobutyric, isovaleric, 2-methylbutyric acids increased INRs.Our provided additional perspective about impact HIV ART, recovery "microbiome-immunity axis" at metabolism level. These factors act as indicators active processes occurring gastrointestinal tract. Individuals HIV-1 displayed unchanged overall bacterial diversity; moreover, their inflammatory status seems not to be completely restored. confirmed role GM metabolites reconstitution.

Language: Английский

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Sustained gut dysbiosis and intestinal inflammation show correlation with weight gain in person with chronic HIV infection on antiretroviral therapy

BMC Microbiology, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 24, 2024

Abstract Background Person with human immunodeficiency virus type-1 (PWH) are prone to chronic inflammation due residual viral production, even antiretroviral therapy (ART), which increases the risk of age-related diseases. There is also limited information on changes in intestinal environment PWH during ART. In this longitudinal study, we investigated gut microbiota, persistence inflammation, interactions between and metabolic using long-term Results We analyzed clinical parameters microbiota 46 over a mean period 4 years understand influence dysbiosis inflammation. Overall, included decrease some bacteria, mainly involved short-chain fatty acid (SCFA) an increase certain opportunistic bacteria. Throughout study period, bacterial-specific activity was observed environment. Continued decline bacteria belonging Clostridia class glucose metabolism. Additionally, patients low abundance Parabacteroides exhibited bacterial alpha diversity significant body mass index (BMI) period. Monocyte chemoattractant protein 1, marker macrophage activation plasma, continued from baseline (first stool collection timepoint) follow-up (second timepoint), demonstrating mild correlation BMI. Elevated BMI moderately correlated elevated levels plasma interleukin 16 chemokine ligand 13, both may play role translocation within microbiota. The rate SCFA-producing such as Anaerostipes Coprococcus 3 . Conclusion Our data suggest that despite effective ART, exhibit persistent associated resulting transition consequences. Moreover, loss correlates weight gain contribute development

Language: Английский

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Impact of HIV infection and integrase strand transfer inhibitors-based treatment on the gut virome

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Dec. 15, 2022

Abstract Viruses are the most abundant components of human gut microbiome with a significant impact on health and disease. The effects immunodeficiency virus (HIV) infection virome has been scarcely analysed. Several studies suggested that integrase strand transfers inhibitors (INSTIs) associated healthier gut. Thus, objective this work was to evaluate HIV INSTIs composition. 26 non-HIV-infected volunteers, 15 naive HIV-infected patients INSTIs-treated were recruited their composition analysed using shotgun sequencing. Bacteriophages diverse viruses present in accompanied by decrease phage richness which reverted after INSTIs-based treatment. β-diversity phages revealed samples from clustered separately those belonging control group. Differential analysis showed an increase Caudoviricetes class group Malgrandaviricetes compared Besides, it observed treatment not able reverse lysogenic or modify relative abundance Proteobacteria-infecting phages. Our study describes for first time demonstrates treatments partially restore dysbiosis at viral level, opens several opportunities new focused microbiota-based therapies.

Language: Английский

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