Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota

Open Forum Infectious Diseases, Journal Year: 2020, Volume and Issue: 7(9)

Published: Aug. 8, 2020

People with HIV (PWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities, and long-term alteration the gut microbiota. Both low CD4/CD8 ratio chronic inflammation have been associated changes in microbiota PWH. The antidiabetic drug metformin has shown to improve composition while decreasing diabetes polycystic ovary syndrome. Nevertheless, it remains unknown whether benefit PWH receiving ART, especially those a ratio.In Lilac pilot trial, we recruited 23 nondiabetic ART for more than 2 years (<0.7). Blood stool samples were collected during study visits at baseline, after 12-week treatment, 12 weeks discontinuation. Microbiota was analyzed by 16S rDNA gene sequencing, markers assessed plasma.Metformin decreased PWH, loss inversely correlated plasma levels satiety factor GDF-15. Furthermore, changed increasing abundance anti-inflammatory bacteria such as butyrate-producing species protective Akkermansia muciniphila.Our provides first evidence that treatment favored ART-treated Larger randomized placebo-controlled clinical trials longer will be needed further investigate role reducing comorbidities

Language: Английский

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Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana

Frontiers in Cellular and Infection Microbiology, Journal Year: 2021, Volume and Issue: 11

Published: May 18, 2021

HIV-1 infected individuals under antiretroviral therapy can control viremia but often develop non-AIDS diseases such as cardiovascular and metabolic disorders. Gut microbiome dysbiosis has been indicated to be associated with progression of these diseases. Analyses gut/fecal in individual regions are important for our understanding pathogenesis infections. However, data on not yet accumulated West Africa. In the present study, we examined fecal compositions adults Ghana, where approximately two-thirds females. a cross-sectional case-control age- gender-matched (HIV+; n = 55) seronegative controls (HIV-; were enrolled. Alpha diversity HIV+ was significantly reduced compared HIV- CD4 counts. showed reduction varieties bacteria including Faecalibacterium , most abundant controls, enrichment Proteobacteria . Ghanaian exhibited Dorea Blautia ; groups whose depletion reported several other cohorts. Furthermore, cohort Prevotella genus recently shown men having sex (MSM) regardless status. The study revealed characteristics dysbiotic representative African populations.

Language: Английский

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Long-Term Suppressive cART Is Not Sufficient to Restore Intestinal Permeability and Gut Microbiota Compositional Changes

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 26, 2021

Background: We explored the long-term effects of cART on markers gut damage, microbial translocation, and paired gut/blood microbiota composition, with a focus role exerted by different drug classes. Methods: enrolled 41 naïve HIV-infected subjects, undergoing blood fecal sampling prior to (T0) after 12 (T12) 24 (T24) months therapy. Fifteen HIV-uninfected individuals were as controls. analyzed: (i) T-cell homeostasis (flow cytometry); (ii) translocation (sCD14, EndoCab, 16S rDNA); (iii) intestinal permeability damage (LAC/MAN, I-FABP, calprotectin); (iv) plasma composition (alpha- beta-diversity, relative abundance); (v) functional metagenome predictions (PICRUSt). Results: Twelve twenty four-month successful resulted in rise EndoCAb (p = 0.0001) I-FABP 0.039) vis-à-vis stable rDNA, sCD14, calprotectin LAC/MAN, along reduced immune activation periphery. Furthermore, did not lead substantial modifications both feces metabolic predictions. The stratification according regimens revealed feeble effect patients NNRTI-based or INSTI-based regimens, but PI-based regimens. Conclusions: hereby show that viro-immunological effective cART, while containing peripheral hyperactivation, exerts only minor gastrointestinal tract. Persistent alteration indicative structural impairment seemingly parallels enduring dysbiosis, irrespective classes, no

Language: Английский

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Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 16, 2023

Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, fecal 16 S microbiome) data-driven stratification to identify at-risk within PWH. Through network analysis similarity fusion (SNF), identified three groups PWH (SNF-1–3): healthy (HC)-like (SNF-1), mild (SNF-3), severe (SNF-2). The SNF-2 (45%) had increased visceral adipose tissue, BMI, higher incidence syndrome (MetS), di- triglycerides despite having CD4 + T-cell counts than other two clusters. However, HC-like group similar differing from HIV-negative controls (HNC), dysregulation amino acid metabolism. At microbiome profile, lower α-diversity, proportion men sex (MSM) was enriched Bacteroides. In contrast, groups, there an increase Prevotella , high MSM, which could potentially lead systemic inflammation cardiometabolic profile. integrative also revealed complex microbial interplay microbiome-associated metabolites Those severely clusters may benefit personalized medicine lifestyle intervention their dysregulated traits, aiming achieve healthier aging.

Language: Английский

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Exercise to Prevent Accelerated Vascular Aging in People Living With HIV

Circulation Research, Journal Year: 2024, Volume and Issue: 134(11), P. 1607 - 1635

Published: May 23, 2024

Given advances in antiretroviral therapy, the mortality rate for HIV infection has dropped considerably over recent decades. However, people living with (PLWH) experience longer life spans coupled persistent immune activation despite viral suppression and potential toxicity from long-term therapy use. Consequently, PLWH face a cardiovascular disease (CVD) risk more than twice that of general population, making it leading cause death among this group. Here, we briefly review epidemiology CVD highlighting disparities at intersections sex gender, age, race/ethnicity, contributions social determinants health psychosocial stress to increased individuals marginalized identities. We then overview pathophysiology discuss primary factors implicated as contributors on therapy. Subsequently, highlight functional evidence premature vascular dysfunction an early pathophysiological determinant PLWH, several mechanisms underlying synthesize current research accelerated aging focusing activation, chronic inflammation, oxidative stress. consider understudied aspects such HIV-related changes gut microbiome stress, which may serve through exercise can abrogate aging. Emphasizing significance exercise, various modalities their impacts health, proposing holistic approach managing risks PLWH. The discussion extends critical future study areas related aging, CVD, efficacy interventions, call inclusive considers diversity population.

Language: Английский

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