SEARCHCOHORTinfectious disease, pediatrics

cohort·infectious disease, pediatrics, gastroenterology, epidemiology, biomedical research·PMC10497879

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

Frontiers in Immunology · 12 authors, 6 centres

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TL;DR

In a cohort of 31 children, the gut microbiota of perinatally HIV-infected children (CLWH) did not differ from that of HIV-unexposed uninfected children (HUU), while sex and markers of chronic immune activation were associated with distinct microbial signatures.

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This cross-sectional cohort study enrolled 31 Mexican children aged 3 to 15 years, including 15 CLWH on long-term suppressive antiretroviral therapy (predominantly protease inhibitor-based) and 16 HUU. Gut microbiota was profiled by 16S rRNA sequencing, and soluble and cellular markers of HIV disease progression were quantified by flow cytometry, ELISA, and multiplex-bead assays. No differences in alpha or beta diversity were found between CLWH and HUU, suggesting long-term ART may normalize gut microbial ecology. Sex influenced microbiota composition, with males showing higher microbial richness and Firmicutes enrichment, and females enriched in Bacteroides. Limitations include the small sample size, cross-sectional design, and inability to perform subgroup analyses by ART regimen.

STUDY TYPE

cohort

SPECIALTY

infectious disease

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ORIGINAL PAPER

PMC10497879

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

Frontiers in Immunology

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ABSTRACT

Introduction Our 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. Methods We 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. Results Children 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). Conclusion The 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.

CITATION EXPORT

Cecilia Rosel-Pech, Sandra Pinto-Cardoso, Monserrat Chávez-Torres et al.. Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection. Frontiers in Immunology. (2023). https://doi.org/10.3389/fimmu.2023.1244473

AUTHORS

12 · 6 CENTRES

Cecilia Rosel-Pech, Sandra Pinto-Cardoso, Monserrat Chávez-Torres, Nadia Montufar, Iván Osuna-Padilla, Santiago Ávila-Ríos, Gustavo Reyes-Terán, Charmina Aguirre-Alvarado, Norma Angelica Matías Juan, Héctor Pérez-Lorenzana, José Guillermo Vázquez-Rosales, Vilma Carolina Bekker-Méndez

1 Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico
2 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
3 Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, Mexico
4 Hospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, Mexico
5 UMAE Hospital General Dr. Gaudencio González Garza, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, Mexico
6 Hospital de Pediatría “Doctor Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México, Mexico