Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection
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 dr...
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1244473/full |
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| author | Cecilia Rosel-Pech 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 |
| author_facet | Cecilia Rosel-Pech 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 |
| author_sort | Cecilia Rosel-Pech |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T12:17:43Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T12:17:43Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9221c2009db84e83ac26592beb0957202023-08-30T08:50:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12444731244473Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infectionCecilia Rosel-Pech0Cecilia Rosel-Pech1Sandra Pinto-Cardoso2Monserrat Chávez-Torres3Nadia Montufar4Iván Osuna-Padilla5Santiago Ávila-Ríos6Gustavo Reyes-Terán7Charmina Aguirre-Alvarado8Norma Angelica Matías Juan9Héctor Pérez-Lorenzana10José Guillermo Vázquez-Rosales11Vilma Carolina Bekker-Méndez12Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoUnidad 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, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoPosgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoUnidad 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, MexicoHospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, MexicoUMAE Hospital General Dr. Gaudencio González Garza, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, MexicoHospital de Pediatría “Doctor Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México, MexicoUnidad 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, MexicoIntroductionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1244473/fullpediatric HIV infectionmother-to-child-transmissiongut microbiomeimmune activationinflammationantibiotics |
| spellingShingle | Cecilia Rosel-Pech 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 Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection Frontiers in Immunology pediatric HIV infection mother-to-child-transmission gut microbiome immune activation inflammation antibiotics |
| title | Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection |
| title_full | Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection |
| title_fullStr | Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection |
| title_full_unstemmed | Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection |
| title_short | Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection |
| title_sort | distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric hiv infection |
| topic | pediatric HIV infection mother-to-child-transmission gut microbiome immune activation inflammation antibiotics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1244473/full |
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