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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2022; 28(6): 635-652
Published online Feb 14, 2022. doi: 10.3748/wjg.v28.i6.635
Effects of viremia and CD4 recovery on gut “microbiome-immunity” axis in treatment-naïve HIV-1-infected patients undergoing antiretroviral therapy
Edda Russo, Giulia Nannini, Gaetana Sterrantino, Seble Tekle Kiros, Vincenzo Di Pilato, Marco Coppi, Simone Baldi, Elena Niccolai, Federica Ricci, Matteo Ramazzotti, Marco Pallecchi, Filippo Lagi, Gian Maria Rossolini, Alessandro Bartoloni, Gianluca Bartolucci, Amedeo Amedei
Edda Russo, Giulia Nannini, Gaetana Sterrantino, Seble Tekle Kiros, Marco Coppi, Simone Baldi, Elena Niccolai, Federica Ricci, Filippo Lagi, Alessandro Bartoloni, Amedeo Amedei, Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
Vincenzo Di Pilato, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa 16126, Italy
Matteo Ramazzotti, Marco Pallecchi, Department of Biomedical, Experimental and Clinical "Mario Serio", University of Florence, Florence 50134, Italy
Gian Maria Rossolini, Microbiology and Virology Unit, Florence Careggi University Hospital, University of Florence, Florence 50134, Italy
Gianluca Bartolucci, Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence 50019, Italy
Author contributions: Russo E and Nannini G contributed equally to the work; Sterrantino G, Russo E, and Amedei A designed the study; Russo E and Sterrantino G revised the literature on this topic; Tekle Kiros S, Niccolai E, Ricci F, Russo E, Baldi S, and Nannini G collected the data; Russo E, Coppi M, Di Pilato V, Nannini G, Baldi S, Ricci F, and Lagi F analysed the data; Ramazzotti M and Di Pilato V performed microbiota analysis; Russo E wrote the manuscript; Russo E edited the manuscript; Amedei A supervised the manuscript; Amedei A, Sterrantino G, Rossolini GM, Bartoucci G, and Bartoloni A revised the manuscript; Russo E, Amedei A, Sterratino G, Bartoloni A, and Rossolini GM provided funding acquisition.
Supported by University of Florence, No. XXXV PhD Program.
Institutional review board statement: The study was reviewed and approved by the Comitato Etico Area Vasta Centro [(Approval No. 15035)].
Conflict-of-interest statement: The authors declare that they have no competing interests to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Amedeo Amedei, BSc, PhD, Professor, Reader (Associate Professor), Department of Clinical and Experimental Medicine, University of Florence, Viale Pieraccini, 6, Florence 50139, Italy. aamedei@unifi.it
Received: May 28, 2021
Peer-review started: May 28, 2021
First decision: June 30, 2021
Revised: July 30, 2021
Accepted: January 13, 2022
Article in press: January 13, 2022
Published online: February 14, 2022
Processing time: 256 Days and 16.9 Hours
ARTICLE HIGHLIGHTS
Research background
Human immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent systemic inflammation and immune activation, even in patients receiving effective antiretroviral therapy (ART). Converging data suggest that gut microbiota (GM) changes can occur throughout including human immunodeficiency virus (HIV) infection treated by ART.
Research motivation
ART has increased the life expectancy of HIV-infected patients; however, chronic inflammation and gut microbiota alterations persist in patients virologically suppressed by ART. These data suggest that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART.
Research objectives
The purpose of this prospective observational study was to compare for the first time the fecal microbial composition, serum and fecal microbial metabolites, and serum cytokine profile of treatment-naïve patients before starting ART and after reaching virological suppression (HIV RNA < 50 copies/mL) after 24 wk of ART.
Research methods
The authors enrolled 12 treatment-naïve HIV-infected patients receiving ART. Fecal microbiota composition was assessed through next generation sequencing, and a comprehensive analysis of a broad spectrum of cytokines in blood was performed through a multiplex approach. In addition, serum free fatty acid (FFA) and fecal short chain fatty acid (SCFA) levels were measured through GC-MS.
Research results
The authors compared microbiota signatures, FFA levels, and cytokine profile before starting ART and after reaching virological suppression. Modest alterations were observed on microbiota composition; moreover, in the same condition, we also observed augmented levels of serum propionic and butyric acids. A reduction of serum IP-10 and an increase of IL-8 level were detected in the viral suppression condition. Thereafter, the same components were compared between immunological responders and non-responders. Concerning the microflora population, we detected a reduction of Faecalibacterium and an increase of Alistipes in immunological non-responders. Simultaneously, fecal isobutyric, isovaleric, and 2-methylbutyric acids were also increased in immunological non-responders.
Research conclusions
The results provid an additional perspective about the impact of HIV infection, ART, and immune recovery on the “microbiome-immunity axis” at the metabolism level. These factors can act as indicators of the active processes occurring in the gastrointestinal tract.
Research perspectives
Future larger-scale, long-term ART and longitudinal studies that include functional metagenomic and metabolomic approaches to identify the roles of the specific differential phylotypes are required to better define the relationship between microbiota-immunity axis and HIV-1 infection and to provide new insights into the targeted treatment, improving the immune recovery and dampening inflammation.
