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<p>The gut microbiome of people living with human immunodeficiency virus (PLWH) has been characterized, but its role in influencing host immunity and associated clinical features are unclear. Here we used shotgun metagenomics to characterize the faecal microbiome of two geographically distinct cohorts of PLWH and healthy controls in Israel and Ethiopia. We uncovered disease-specific, geographically divergent microbial patterns including a shift from <i>Bacteroides</i> to <i>Prevotella</i> species in an Israeli cohort and multiple Enterobacteriaceae species including <i>Escherichia coli</i> and <i>Klebsiella quasivariicola</i> in an Ethiopian cohort. We identified correlations between human immunodeficiency virus-related dysbiosis and the extent of systemic immunodeficiency, as proxied by peripheral CD4<sup>+</sup> T cell counts. Faecal microbiome transplantation from PLWH with high peripheral CD4<sup>+</sup> T cell counts induced colonic epithelium-associated CD4<sup>+</sup> T cells in germ-free or antibiotic-treated recipient mice. Impaired epithelium-associated lymphocyte induction in recipients of faecal microbiome transplantation from severely immunodeficient PLWH donors was associated with altered protection from <i>Cryptosporidium parvum</i> infection. Collectively, our results suggest a link between systemic immunodeficiency and associated intestinal dysbiosis in PLWH, resulting in impaired gut mucosal immunity.</p>

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Human immunodeficiency virus-associated gut microbiome impacts systemic immunodeficiency and susceptibility to opportunistic gut infection

  • 期刊论文

  • 发表日期：

    2026年2月16日

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  • Stavros Bashiardes,
  • Melina Heinemann,
  • Lorenz Adlung,
  • Rafael Valdés-Mas,
  • Jemal Ali Mahdi,
  • Samuel P. Nobs,
  • Timur Tuganbaev,
  • Takahiro Yamada,
  • Max Horn,
  • Uria Mor,
  • Yotam Cohen,
  • Sarah Israel,
  • Maya Korem,
  • Yonatan Oster,
  • Karen Olshtain-Pops,
  • Efrat Orenbuch-Harroch,
  • Muhammed Dervis Arslan,
  • Shahar Molina,
  • Maya Zur,
  • Shimrit Eliyahu-Miller,
  • Aurélie Bukimer,
  • Sara Federici,
  • Mally Dori-Bachash,
  • Nira Amar,
  • Daniel Elbirt,
  • Ronit Cohen-Poradosu,
  • Dan Turner,
  • Tiberiu Hershcovici,
  • Elez Vainer,
  • Noa Stettner,
  • Alon Harmelin,
  • Hailay Gebremeskel,
  • Yazezew Kebede,
  • Sabine Schmidt,
  • Niv Zmora,
  • Arunraj Dhamodaran,
  • Jens Puschhof,
  • Zvi Bentwich,
  • Hagit Shapiro,
  • Ido Amit,
  • Hila Elinav,
  • Eran Elinav

摘要

The gut microbiome of people living with human immunodeficiency virus (PLWH) has been characterized, but its role in influencing host immunity and associated clinical features are unclear. Here we used shotgun metagenomics to characterize the faecal microbiome of two geographically distinct cohorts of PLWH and healthy controls in Israel and Ethiopia. We uncovered disease-specific, geographically divergent microbial patterns including a shift from Bacteroides to Prevotella species in an Israeli cohort and multiple Enterobacteriaceae species including Escherichia coli and Klebsiella quasivariicola in an Ethiopian cohort. We identified correlations between human immunodeficiency virus-related dysbiosis and the extent of systemic immunodeficiency, as proxied by peripheral CD4+ T cell counts. Faecal microbiome transplantation from PLWH with high peripheral CD4+ T cell counts induced colonic epithelium-associated CD4+ T cells in germ-free or antibiotic-treated recipient mice. Impaired epithelium-associated lymphocyte induction in recipients of faecal microbiome transplantation from severely immunodeficient PLWH donors was associated with altered protection from Cryptosporidium parvum infection. Collectively, our results suggest a link between systemic immunodeficiency and associated intestinal dysbiosis in PLWH, resulting in impaired gut mucosal immunity.