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      A gut microbiome signature for HIV and metabolic dysfunction-associated steatotic liver disease

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          Abstract

          Introduction

          Metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver axis is considered to be strongly implicated in the pathogenesis of MASLD. We aimed to characterize the gut microbiota composition in PLWH and MASLD and compare it with that of two control groups: PLWH without MASLD and individuals with MASLD without HIV infection.

          Methods

          We collected clinical data and stool samples from participants. Bacterial 16S rRNA genes were amplified, sequenced, and clustered into operational taxonomic unit. Alpha diversity was studied by Shannon and Simpson indexes. To study how different the gut microbiota composition is between the different groups, beta diversity estimation was evaluated by principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity. To further analyze differences in microbiome composition we performed a linear discriminant analysis (LDA) effect size (LEfSe).

          Results

          We included 30 HIV +MASLD +, 30 HIV +MASLD - and 20 HIV -MASLD + participants. Major butyrate producers, including Faecalibacterium, Ruminococcus, and Lachnospira dominated the microbiota in all three groups. Shannon’s and Simpson’s diversity metrics were higher among MASLD + individuals (Kruskal-Wallis p = 0.047). Beta diversity analysis showed distinct clustering in MASLD -, with MASLD + participants overlapping regardless of HIV status (ADONIS significance <0.001). MASLD was associated with increased homogeneity across individuals, in contrast to that observed in the HIV+NAFDL- group, in which the dispersion was higher (Permanova test, p value <0.001; ANOSIM, p value <0.001). MASLD but not HIV determined a different microbiota structure (HIV +MASLD- vs. HIV +MASLD +, q-value = 0.002; HIV -MASLD + vs. HIV +MASLD +, q-value = 0.930; and HIV -MASLD + vs. HIV +MASLD -, q-value < 0.001). The most abundant genera in MASLD- were Prevotella, Bacteroides, Dialister, Acidaminococcos, Alloprevotella, and Catenibacterium. In contrast, the most enriched genera in MASLD+ were Ruminococcus, Streptococcus, Holdemanella, Blautia, and Lactobacillus.

          Conclusions

          We found a microbiome signature linked to MASLD, which had a greater influence on the overall structure of the gut microbiota than HIV status alone.

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          Most cited references42

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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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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              ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R

              After more than fifteen years of existence, the R package ape has continuously grown its contents, and has been used by a growing community of users. The release of version 5.0 has marked a leap towards a modern software for evolutionary analyses. Efforts have been put to improve efficiency, flexibility, support for 'big data' (R's long vectors), ease of use and quality check before a new release. These changes will hopefully make ape a useful software for the study of biodiversity and evolution in a context of increasing data quantity.
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                Author and article information

                Contributors
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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                14 December 2023
                2023
                : 14
                : 1297378
                Affiliations
                [1] 1 Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Madrid, Spain
                [2] 2 CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid, Spain
                [3] 3 Universidad Complutense de Madrid (UCM) , Madrid, Spain
                [4] 4 Department of Nutrition and Food Science, Complutense University of Madrid , Madrid, Spain
                [5] 5 HIV Unit - Internal Medicine Service, Hospital Universitario La Paz , Madrid, Spain
                [6] 6 Department of Gastroenterology and Hepatology, Metabolic Liver Disease Clinic, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Madrid, Spain
                Author notes

                Edited by: Jaime Federico Andrade-Villanueva, University of Guadalajara, Mexico

                Reviewed by: Monserrat Alvarez, Centro de Investigación Biomédica de Occidente, Mexico

                Shaoyi Zhang, University of California, San Francisco, United States

                *Correspondence: Javier Martínez-Sanz, javier.martinez.sanz@ 123456salud.madrid.org ; Matilde Sánchez-Conde, mariamatilde.sanchez@ 123456salud.madrid.org

                †These authors have contributed equally to this work

                ‡These authors share senior authorship

                Article
                10.3389/fimmu.2023.1297378
                10755913
                a569f3b9-ec84-4821-9763-d3ddc18b4732
                Copyright © 2023 Martínez-Sanz, Talavera-Rodríguez, Díaz-Álvarez, Rosas Cancio-Suárez, Rodríguez, Alba, Montes, Martín-Mateos, Burgos-Santamaría, Moreno, Serrano-Villar and Sánchez-Conde

                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
                : 20 September 2023
                : 24 November 2023
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 42, Pages: 0, Words: 4200
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Instituto de Salud Carlos III project PI17/01717 Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016. Co-funded by European Regional Development Fund “a way to make Europe”.
                Categories
                Immunology
                Original Research
                Custom metadata
                Microbial Immunology

                Immunology
                hiv,masld,nafld,gut microbiome,microbiome
                Immunology
                hiv, masld, nafld, gut microbiome, microbiome

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