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

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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.

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          Most cited references84

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          DADA2: High resolution sample inference from Illumina amplicon data

          We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
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            The SILVA ribosomal RNA gene database project: improved data processing and web-based tools

            SILVA (from Latin silva, forest, http://www.arb-silva.de) is a comprehensive web resource for up to date, quality-controlled databases of aligned ribosomal RNA (rRNA) gene sequences from the Bacteria, Archaea and Eukaryota domains and supplementary online services. The referred database release 111 (July 2012) contains 3 194 778 small subunit and 288 717 large subunit rRNA gene sequences. Since the initial description of the project, substantial new features have been introduced, including advanced quality control procedures, an improved rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. Furthermore, the extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches.
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              Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2

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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2361519
                URI : https://loop.frontiersin.org/people/1765167
                URI : https://loop.frontiersin.org/people/1796868
                URI : https://loop.frontiersin.org/people/1778290
                URI : https://loop.frontiersin.org/people/1525360
                URI : https://loop.frontiersin.org/people/666937
                URI : https://loop.frontiersin.org/people/942961
                URI : https://loop.frontiersin.org/people/2394495
                URI : https://loop.frontiersin.org/people/1078484
                URI : https://loop.frontiersin.org/people/938627
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                29 August 2023
                2023
                : 14
                : 1244473
                Affiliations
                [1] 1 Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM) , Ciudad de México, Mexico
                [2] 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] 3 Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , Ciudad de México, Mexico
                [4] 4 Hospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS) , Ciudad de México, Mexico
                [5] 5 UMAE Hospital General Dr. Gaudencio González Garza, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS) , Ciudad de México, Mexico
                [6] 6 Hospital de Pediatría “Doctor Silvestre Frenk Freund”, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social , México, Mexico
                Author notes

                Edited by: Nicholas Funderburg, The Ohio State University, United States

                Reviewed by: Tiffany Hensley-McBain, McLaughlin Research Institutes, United States; Modupe Coker, The State University of New Jersey, United States

                *Correspondence: Sandra Pinto-Cardoso, sandra.pintocardoso.cieni@ 123456gmail.com ; Vilma Carolina Bekker-Méndez, bekkermendez@ 123456yahoo.com

                †These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fimmu.2023.1244473
                10497879
                37711620
                7153a8f8-a4c1-4461-9515-58932d7cdd6f
                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

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 June 2023
                : 09 August 2023
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 88, Pages: 15, Words: 8667
                Funding
                Funded by: Consejo Nacional de Ciencia y Tecnología , doi 10.13039/501100003141;
                Funded by: Instituto Mexicano del Seguro Social , doi 10.13039/501100004881;
                This work was supported by grants from Apoyo financiero para el desarrollo de protocolos de investigación y desarrollo tecnológico sobre temas específicos de los temas prioritarios de salud del Instituto Mexicano del Seguro Social (Fondo de Investigación en Salud FIS/IMSS/PROT/PRIO/19/097 R-2018-785-130), Programa Presupuestario F003 “Programas Nacionales Estratégicos de Ciencia,. Tecnología y Vinculación con los Sectores Social, Público y Privado” Dirección de Ciencia de Frontera, Consejo Nacional de Humanidades Ciencias y Tecnologías (CONAHCYT, Convocatoria Ciencia de Frontera 2019 formely FORDECYT-PRONACES/140641/2020) and the Programa Presupuestal P016, Anexo 13 del Decreto del Presupuesto de Egresos de la Federación.
                Categories
                Immunology
                Original Research
                Custom metadata
                Viral Immunology

                Immunology
                pediatric hiv infection,mother-to-child-transmission,gut microbiome,immune activation,inflammation,antibiotics,healthy eating index

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