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Association between CD4(+) T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders

BACKGROUND: CD4(+) T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflam...

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Autores principales: Lu, Danfeng, Zhang, Jian-Bo, Wang, Yue-Xin, Geng, Shi-Tao, Zhang, Zunyue, Xu, Yu, Li, Shao-You, Wang, Kun-Hua, Kuang, Yi-Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336095/
https://www.ncbi.nlm.nih.gov/pubmed/34344350
http://dx.doi.org/10.1186/s12879-021-06491-z
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author Lu, Danfeng
Zhang, Jian-Bo
Wang, Yue-Xin
Geng, Shi-Tao
Zhang, Zunyue
Xu, Yu
Li, Shao-You
Wang, Kun-Hua
Kuang, Yi-Qun
author_facet Lu, Danfeng
Zhang, Jian-Bo
Wang, Yue-Xin
Geng, Shi-Tao
Zhang, Zunyue
Xu, Yu
Li, Shao-You
Wang, Kun-Hua
Kuang, Yi-Qun
author_sort Lu, Danfeng
collection PubMed
description BACKGROUND: CD4(+) T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4(+) T cell counts in HIV-infected individuals. However, the association between CD4(+) T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4(+) T cell counts < 500 cells/μL) from Yunnan Province, China, has not been previously investigated. METHODS: To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count < 200 cells/μL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8(+) T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups. RESULTS: Compared to INRs with CD4 count > 200 cells/μL, those with CD4 count < 200 cells/μL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/μL group than in the CD4 count > 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4(+) T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae. CONCLUSIONS: Our study demonstrated that lower CD4(+) T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4(+) T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06491-z.
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spelling pubmed-83360952021-08-04 Association between CD4(+) T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders Lu, Danfeng Zhang, Jian-Bo Wang, Yue-Xin Geng, Shi-Tao Zhang, Zunyue Xu, Yu Li, Shao-You Wang, Kun-Hua Kuang, Yi-Qun BMC Infect Dis Research BACKGROUND: CD4(+) T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4(+) T cell counts in HIV-infected individuals. However, the association between CD4(+) T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4(+) T cell counts < 500 cells/μL) from Yunnan Province, China, has not been previously investigated. METHODS: To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count < 200 cells/μL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8(+) T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups. RESULTS: Compared to INRs with CD4 count > 200 cells/μL, those with CD4 count < 200 cells/μL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/μL group than in the CD4 count > 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4(+) T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae. CONCLUSIONS: Our study demonstrated that lower CD4(+) T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4(+) T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06491-z. BioMed Central 2021-08-03 /pmc/articles/PMC8336095/ /pubmed/34344350 http://dx.doi.org/10.1186/s12879-021-06491-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Lu, Danfeng
Zhang, Jian-Bo
Wang, Yue-Xin
Geng, Shi-Tao
Zhang, Zunyue
Xu, Yu
Li, Shao-You
Wang, Kun-Hua
Kuang, Yi-Qun
Association between CD4(+) T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders
title Association between CD4(+) T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders
title_full Association between CD4(+) T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders
title_fullStr Association between CD4(+) T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders
title_full_unstemmed Association between CD4(+) T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders
title_short Association between CD4(+) T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders
title_sort association between cd4(+) t cell counts and gut microbiota and serum cytokines levels in hiv-infected immunological non-responders
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336095/
https://www.ncbi.nlm.nih.gov/pubmed/34344350
http://dx.doi.org/10.1186/s12879-021-06491-z
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