Changes of the intestinal microbiome—host homeostasis in HIV-infected individuals — a focus on the bacterial gut microbiome

Ribeiro, Ana Beatriz Dein Terra Mota; Heimesaat, Markus M.; Bereswill, Stefan

doi:10.1556/1886.2017.00016

Cited by 28 publications

(13 citation statements)

References 42 publications

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“…It is now widely accepted that, aside from the direct effect on gastrointestinal mucosal immunity (45)(46)(47)(48), HIV infection is characterized by gut microbiota compositional and functional changes, not fully reverted by cART (1,3,5,12,13,18,(49)(50)(51)(52)(53). However, the causal relationship between altered intestinal microbiota composition, gut damage, and cART remains an open question that needs to be answered in order to improve microbiome-targeted therapies.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Interestingly, a landmark study recently showed no effect of experimental gut microbiota dysbiosis on disease progression in an SIV infection model, indicating that the associations we observed in PLWHA may result from the confounders (Ortiz et al, 2018). Therefore, we suggest that future microbiome studies on HIV infection should take these confounders into consideration (Noguera-Julian et al, 2016; Tincati et al, 2016; Ribeiro et al, 2017; Hamad et al, 2018; Klatt and Manuzak, 2018; Williams et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…In HIV-infection, leaky gut and an increased plasma level of microbiota products contribute to immune activation, which has been linked to HAND (Eden et al, 2007; Sandler and Douek, 2012; Yilmaz et al, 2013; Eden et al, 2016). Furthermore, gut microbiota dysbiosis is common in HIV-infection, especially in those with low CD4 T-cell counts (Tincati et al, 2016; Ribeiro et al, 2017; Hamad et al, 2018; Williams et al, 2018). Whether gut microbiota play a role in the pathogenesis of HAND, currently remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Dysbiosis Is Not Independently Associated With Neurocognitive Impairment in People Living With HIV

Zhang

Yang

et al. 2019

Front. Microbiol.

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Gut microbiota dysbiosis, which has been linked to many neurological diseases, is common in HIV infection. However, its role in the pathogenesis of neurocognitive impairment is still not established. In this study, a total of 85 HIV infected subjects, naïve to antiretroviral therapy, were classified into two groups—those with HIV-associated neurological diseases (HAND) and those without, using the Montreal Cognitive Assessment (MoCA) test. Fecal samples were collected from all subjects and microbiota were analyzed by 16S rRNA amplicon sequencing. Subjects with HAND were older (P < 0.001), with lower levels of education (P = 0.002), lower CD4 T-cell counts (P = 0.032), and greater heterosexual preference (P < 0.001), than those without HAND. Gut microbiota from subjects with HAND showed significantly lower α-diversity compared to gut microbiota from subjects without HAND (Shannon index, P = 0.003). To exclude confounding bias, 25 subjects from each group, with comparable age, gender, CD4 T-cell count, educational level and sexual preference were further analyzed. The two groups showed comparable α-diversity (for SOB index, Shannon index, Simpson index, ACE index, and Chao index, all with P-value > 0.05) and β-diversity (ANOSIM statistic = 0.010, P = 0.231). There were no significant differences in microbiota composition between the two groups after the correction for a false discovery rate. Consistently, microbiota from the two groups presented similar predictive functional profiles. Gut microbiota dysbiosis is not independently associated with neurocognitive impairment in people living with HIV.

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“…The one anatomic region that revealed a decrease in identical sequences and an increase in unique sequences was the gut; however, the findings in the gut did not reach statistical significance. This suggests that cells located in the gut are under strict immune regulation preventing their response to normal gut flora, which limits cellular proliferation and expansion of identical HIV-1 sequences (66)(67)(68)(69)(70).…”

Section: Fig 14mentioning

confidence: 99%

Impact of Antiretroviral Therapy Duration on HIV-1 Infection of T Cells within Anatomic Sites

Lee

Stockenström

Morcilla

et al. 2020

J Virol

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Understanding the impact of antiretroviral therapy (ART) duration on HIV-infected cells is critical for developing successful curative strategies. To address this issue, we conducted a cross-sectional/inter-participant genetic characterization of HIV-1 RNA from pre- and on-therapy plasmas and HIV-1 DNA from CD4+ T cell subsets derived from peripheral blood (PB), lymph node (LN), and gut tissues of 26 participants after 3 to 17.8 years of ART. Our studies revealed in four acute/early participants who had paired PB and LN samples a substantial reduction in the proportion of HIV-infected cells per year on therapy within the LN. Extrapolation to all 12 acute/early participants estimated a much smaller reduction in the proportion of HIV-1-infected cells within LNs per year on therapy that was similar to that in the participants treated during chronic infection. LN-derived effector memory T (TEM) cells contained HIV-1 DNA that was genetically identical to viral sequences derived from pre- and on-therapy plasma samples. The proportion of identical HIV-1 DNA sequences increased within PB-derived TEM cells. However, the infection frequency of TEM cells in PB was stable, indicating that cellular proliferation that compensates for T cell loss over time contributes to HIV-1 persistence. This study suggests that ART reduces HIV-infected T cells and that clonal expansion of HIV-infected cells maintains viral persistence. Importantly, LN-derived TEM cells are a probable source of HIV-1 genomes capable of producing infectious HIV-1 and should be targeted by future curative strategies. IMPORTANCE HIV-1 persists as an integrated genome in CD4+ memory T cells during effective therapy, and cessation of current treatments results in resumption of viral replication. To date, the impact of antiretroviral therapy duration on HIV-infected CD4+ T cells and the mechanisms of viral persistence in different anatomic sites is not clearly elucidated. In the current study, we found that treatment duration was associated with a reduction in HIV-infected T cells. Our genetic analyses revealed that CD4+ effector memory T (TEM) cells derived from the lymph node appeared to contain provirus that was genetically identical to plasma-derived virions. Moreover, we found that cellular proliferation counterbalanced the decay of HIV-infected cells throughout therapy. The contribution of cellular proliferation to viral persistence is particularly significant in TEM cells. Our study emphasizes the importance of HIV-1 intervention and provides new insights into the location of memory T cells infected with HIV-1 DNA, which is capable of contributing to viremia.

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Changes of the intestinal microbiome—host homeostasis in HIV-infected individuals — a focus on the bacterial gut microbiome

Cited by 28 publications

References 42 publications

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

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

Gut Microbiota Dysbiosis Is Not Independently Associated With Neurocognitive Impairment in People Living With HIV

Impact of Antiretroviral Therapy Duration on HIV-1 Infection of T Cells within Anatomic Sites

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