Partial restoration of gut‐mucosal dysbiosis in late‐treated HIV‐infected subjects with CD4 T‐cell recovery

Olivas-Martínez, Israel; Rosado‐Sánchez, Isaac; Varela, Juan Antonio Cordero; Sobrino, Salvador; Genebat, Miguel; Herrero-Fernández, Inés; Pablos, Rocío M. de; Carvajal, Ana E.; Ruiz, Rocío; Álvarez-Ríos, Ana Isabel; Fontillón-Alberdi, M.; Bulnes-Ramos, Ángel; Garrido-Rodríguez, Vanesa; Pozo-Balado, María del Mar; Leal, Manuel; Pacheco, Yolanda M.

doi:10.1002/ctm2.788

Cited by 6 publications

(7 citation statements)

References 10 publications

(15 reference statements)

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“…This study revealed an increase in faecal Prevotellaceae abundance in INRs, which was associated with a reduction in gut IGKC + IgA + plasma cells. This is consistent with the partial restoration of intestinal microbial balance in late‐treated PLWH 41 . Prevotella abundance has been positively related to the overactivation of mucosal T cells and myeloid DCs 4 .…”

Section: Discussionsupporting

confidence: 87%

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Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non‐responders

Wang,

Zhen,

Guo

et al. 2024

Clinical & Translational Med

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BackgroundThe gut is an important site for human immunodeficiency virus (HIV) infection and immune responses. The role of gut mucosal immune cells in immune restoration in patients infected with HIV undergoing antiretroviral therapy remains unclear.MethodsIleocytes, including 54 475 immune cells, were obtained from colonoscopic biopsies of five HIV‐negative controls, nine immunological responders (IRs), and three immunological non‐responders (INRs) and were analyzed using single‐cell RNA sequencing. Immunohistochemical assays were performed for validation. The 16S rRNA gene was amplified using PCR in faecal samples to analyze faecal microbiota. Flow cytometry was used to analyze CD4+ T‐cell counts and the activation of T cells.ResultsThis study presents a global transcriptomic profile of the gut mucosal immune cells in patients infected with HIV. Compared with the IRs, the INRs exhibited a lower proportion of gut plasma cells, especially the IGKC+IgA+ plasma cell subpopulation. IGKC+IgA+ plasma cells were negatively associated with enriched f. Prevotellaceae the INRs and negatively correlated with the overactivation of T cells, but they were positively correlated with CD4+ T‐cell counts. The INRs exhibited a higher proportion of B cells than the IRs. Follicular and memory B cells were significantly higher in the INRs. Reduced potential was observed in the differentiation of follicular or memory B cells into gut plasma cells in INRs. In addition, the receptor‐ligand pairs CD74_MIF and CD74_COPA of memory B/ follicular helper T cells were significantly reduced in the INRs, which may hinder the differentiation of memory and follicular B cells into plasma cells.ConclusionsOur study shows that plasma cells are dysregulated in INRs and provides an extensive resource for deciphering the immune pathogenesis of HIV in INRs.Key points An investigation was carried out at the single‐cell‐level to analyze gut mucosal immune cells alterations in PLWH after ART. B cells were significantly increased and plasma cells were significantly decreased in the INRs compared to the IRs and NCs. There are gaps in the transition from gut follicular or memory B cellsinto plasma cells in INRs.

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Section: Discussionsupporting

confidence: 87%

“…This is consistent with the partial restoration of intestinal microbial balance in late-treated PLWH. 41 Prevotella abundance has been positively related to the overactivation of mucosal T cells and myeloid DCs. 4 Prevotella is also associated with inflammation, opportunistic infections, and autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non‐responders

Wang,

Zhen,

Guo

et al. 2024

Clinical & Translational Med

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“…To shed light on the questions above, a recent paper by Olivas-Martínez et al 8 attempts to address the microbiome composition of HIV patients based on their treatment regimen and immunological outcome. Due to differences in populations, local diet, sampling, and analysis techniques, previous assessments according to immune response following infection and cART have been lacking or challenging to interpret when compared with each other.…”

Section: Hiv and The Microbiomementioning

confidence: 99%

“…To shed light on the questions above, a recent paper by Olivas‐Martínez et al 8 . attempts to address the microbiome composition of HIV patients based on their treatment regimen and immunological outcome.…”

Section: Hiv and The Microbiomementioning

confidence: 99%

HIV‐associated dysbiosis and immune recovery during antiretroviral therapy

Johnson

Byrareddy

2022

Clinical and Translational Dis

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The microbiomes of people living with HIV (PLWH) are significantly dysregulated with a loss of bacteria diversity and shifts in composition, including increases in pathogenic and decreases in beneficial species. Because of the microbiome's role in modulating health, the effect of this dysbiosis on immune response in PLWH has been a significant concern, mainly because these shifts can persist even after viral suppression during combination antiretroviral therapy (cART). However, due to limitations on sample availability, few studies have been able to provide insights into these microbiome‐immune interactions. Recently, Olivas‐Martínez et al. characterized ileum and caecum mucosa‐associated microbiomes of PLWH based on their level of peripheral CD4+ T‐cell reconstitution following long‐term cART. Their analysis revealed distinct microbiome signatures predictive of recovery. Additionally, differences in markers of gut inflammation and damage between response groups were described, further implicating mucosal disruptions with immune reconstitution. These new data demonstrate an interdependence of microbiome and therapy response, and additional studies are urgently required to fully elucidate this crosstalk and microbiome dynamics from before/after infection and finally, long‐term viral suppression with cART.

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“…In addition to standard ART, more alternative therapies such as fecal microbiota transplantation, predigested protein enteral nutritional supplementation, immunosuppressant supplementation, and human umbilical cord mesenchymal stem cell transfusion have been used to promote immune recovery in HIV/AID‐INRs. It has recently been shown that gut microbial metabolism can affect the immune recovery inpatients infected with HIV (Lee et al, 2018; Vujkovic‐Cvijin & Somsouk, 2019), and fecal microbiota transplantation in HIV patients can promote immune recovery (Olivas‐Martinez et al, 2022; Serrano‐Villar et al, 2021). Moreover, a study has shown that malnutrition promotes the transformation of the immune cell phenotype into a pro‐inflammatory phenotype, maintains a chronic inflammatory state, and then affects immune recovery (Feria et al, 2018; Nishimura et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders

Zheng

et al. 2022

The Anatomical Record

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HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS‐INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS‐INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS‐INRs. In our study, to identify the typical HIV/AIDS‐INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography–tandem mass spectrometry (TMT‐LC–MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome‐specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs‐INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS‐INRs.

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Partial restoration of gut‐mucosal dysbiosis in late‐treated HIV‐infected subjects with CD4 T‐cell recovery

Cited by 6 publications

References 10 publications

Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non‐responders

Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non‐responders

HIV‐associated dysbiosis and immune recovery during antiretroviral therapy

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders

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