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