Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection

Frontiers in Immunology

Immunology

Monserrat Chávez-Torres¹  Santiago Ávila-Ríos¹  Sandra Pinto-Cardoso¹  Nadia Montufar¹  Iván Osuna-Padilla¹  Norma Angelica Matías Juan²  José Guillermo Vázquez-Rosales³  Gustavo Reyes-Terán⁴  Cecilia Rosel-Pech⁵  Héctor Pérez-Lorenzana⁶  Charmina Aguirre-Alvarado⁷  Vilma Carolina Bekker-Méndez⁷ 

[1] Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, Mexico;Hospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, Mexico;Hospital de Pediatría “Doctor Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México, Mexico;Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico;Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico;Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, Mexico;UMAE Hospital General Dr. Gaudencio González Garza, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, Mexico;Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, Mexico;

关键词: pediatric HIV infection;    mother-to-child-transmission;    gut microbiome;    immune activation;    inflammation;    antibiotics;    healthy eating index;   

DOI  :  10.3389/fimmu.2023.1244473

 received in 2023-06-22, accepted in 2023-08-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionOur understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children.MethodsWe enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata.ResultsChildren had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively).ConclusionThe gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.

【 授权许可】

Unknown   
Copyright © 2023 Rosel-Pech, Pinto-Cardoso, Chávez-Torres, Montufar, Osuna-Padilla, Ávila-Ríos, Reyes-Terán, Aguirre-Alvarado, Matías Juan, Pérez-Lorenzana, Vázquez-Rosales and Bekker-Méndez