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Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. Modifications of gut microbiota seem to be associated with the disease, but the impact of gut microbiota on therapies’ outcome remains unclear. A role of T cells in RA pathogenesis has been addressed, particularly on the Th17/Treg c...

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Autores principales: Marazzato, Massimiliano, Iannuccelli, Cristina, Guzzo, Maria Paola, Nencioni, Lucia, Lucchino, Bruno, Radocchia, Giulia, Gioia, Chiara, Bonfiglio, Giulia, Neroni, Bruna, Guerrieri, Francesca, Pantanella, Fabrizio, Garzoli, Stefania, Vomero, Marta, Barbati, Cristiana, Di Franco, Manuela, Schippa, Serena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304627/
https://www.ncbi.nlm.nih.gov/pubmed/35872763
http://dx.doi.org/10.3389/fmed.2022.921675
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author Marazzato, Massimiliano
Iannuccelli, Cristina
Guzzo, Maria Paola
Nencioni, Lucia
Lucchino, Bruno
Radocchia, Giulia
Gioia, Chiara
Bonfiglio, Giulia
Neroni, Bruna
Guerrieri, Francesca
Pantanella, Fabrizio
Garzoli, Stefania
Vomero, Marta
Barbati, Cristiana
Di Franco, Manuela
Schippa, Serena
author_facet Marazzato, Massimiliano
Iannuccelli, Cristina
Guzzo, Maria Paola
Nencioni, Lucia
Lucchino, Bruno
Radocchia, Giulia
Gioia, Chiara
Bonfiglio, Giulia
Neroni, Bruna
Guerrieri, Francesca
Pantanella, Fabrizio
Garzoli, Stefania
Vomero, Marta
Barbati, Cristiana
Di Franco, Manuela
Schippa, Serena
author_sort Marazzato, Massimiliano
collection PubMed
description Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. Modifications of gut microbiota seem to be associated with the disease, but the impact of gut microbiota on therapies’ outcome remains unclear. A role of T cells in RA pathogenesis has been addressed, particularly on the Th17/Treg cells balance. Our study aimed to evaluate in early RA (ERA) patients compared to a control group, fecal gut microbiota composition, short-chain fatty acids concentrations, and the levels of circulating Th17/Treg and their own cytokines, before and after 3 months of standard treatment (Methotrexate (MTX) plus glucocorticoids). Fecal microbiota characterization was carried out on 19 ERA patients and 20 controls matched for sex and age. Significant decreased biodiversity levels, and a partition on the base of the microbiota composition, between the ERA patients at baseline compared to controls, were observed. The co-occurrent analysis of interactions revealed a characteristic clustered structure of the microbial network in controls that is lost in ERA patients where an altered connection between microbes and clinical parameters/metabolites has been reported. Microbial markers such as Acetanaerobacterium elongatum, Cristiansella massiliensis, and Gracilibacter thermotolerans resulted significantly enriched in control group while the species Blautia gnavus emerged to be more abundant in ERA patients. Our results showed an alteration in Th17/Treg balance with higher Th17 levels and lower Treg levels in ERA group respect to control at baseline, those data improved after therapy. Treatment administration and the achievement of a low disease activity/remission appear to exert a positive pressure on the structure of intestinal microbiota with the consequent restoration of biodiversity, of the structure of microbial network, and of the abundance of taxa that became closer to those presented by the subject without the disease. We also found an association between Blautia gnavus and ERA patients characterized by a significant reduction of propionic acid level. Furthermore significant differences highlighted at baseline among controls and ERA patients are no more evident after treatment. These data corroborate the role played by gut microbiota in the disease and suggest that therapy aimed to restore gut microbiota would improve treatment outcome.
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spelling pubmed-93046272022-07-23 Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study Marazzato, Massimiliano Iannuccelli, Cristina Guzzo, Maria Paola Nencioni, Lucia Lucchino, Bruno Radocchia, Giulia Gioia, Chiara Bonfiglio, Giulia Neroni, Bruna Guerrieri, Francesca Pantanella, Fabrizio Garzoli, Stefania Vomero, Marta Barbati, Cristiana Di Franco, Manuela Schippa, Serena Front Med (Lausanne) Medicine Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. Modifications of gut microbiota seem to be associated with the disease, but the impact of gut microbiota on therapies’ outcome remains unclear. A role of T cells in RA pathogenesis has been addressed, particularly on the Th17/Treg cells balance. Our study aimed to evaluate in early RA (ERA) patients compared to a control group, fecal gut microbiota composition, short-chain fatty acids concentrations, and the levels of circulating Th17/Treg and their own cytokines, before and after 3 months of standard treatment (Methotrexate (MTX) plus glucocorticoids). Fecal microbiota characterization was carried out on 19 ERA patients and 20 controls matched for sex and age. Significant decreased biodiversity levels, and a partition on the base of the microbiota composition, between the ERA patients at baseline compared to controls, were observed. The co-occurrent analysis of interactions revealed a characteristic clustered structure of the microbial network in controls that is lost in ERA patients where an altered connection between microbes and clinical parameters/metabolites has been reported. Microbial markers such as Acetanaerobacterium elongatum, Cristiansella massiliensis, and Gracilibacter thermotolerans resulted significantly enriched in control group while the species Blautia gnavus emerged to be more abundant in ERA patients. Our results showed an alteration in Th17/Treg balance with higher Th17 levels and lower Treg levels in ERA group respect to control at baseline, those data improved after therapy. Treatment administration and the achievement of a low disease activity/remission appear to exert a positive pressure on the structure of intestinal microbiota with the consequent restoration of biodiversity, of the structure of microbial network, and of the abundance of taxa that became closer to those presented by the subject without the disease. We also found an association between Blautia gnavus and ERA patients characterized by a significant reduction of propionic acid level. Furthermore significant differences highlighted at baseline among controls and ERA patients are no more evident after treatment. These data corroborate the role played by gut microbiota in the disease and suggest that therapy aimed to restore gut microbiota would improve treatment outcome. Frontiers Media S.A. 2022-07-08 /pmc/articles/PMC9304627/ /pubmed/35872763 http://dx.doi.org/10.3389/fmed.2022.921675 Text en Copyright © 2022 Marazzato, Iannuccelli, Guzzo, Nencioni, Lucchino, Radocchia, Gioia, Bonfiglio, Neroni, Guerrieri, Pantanella, Garzoli, Vomero, Barbati, Di Franco and Schippa. https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Medicine
Marazzato, Massimiliano
Iannuccelli, Cristina
Guzzo, Maria Paola
Nencioni, Lucia
Lucchino, Bruno
Radocchia, Giulia
Gioia, Chiara
Bonfiglio, Giulia
Neroni, Bruna
Guerrieri, Francesca
Pantanella, Fabrizio
Garzoli, Stefania
Vomero, Marta
Barbati, Cristiana
Di Franco, Manuela
Schippa, Serena
Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study
title Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study
title_full Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study
title_fullStr Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study
title_full_unstemmed Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study
title_short Gut Microbiota Structure and Metabolites, Before and After Treatment in Early Rheumatoid Arthritis Patients: A Pilot Study
title_sort gut microbiota structure and metabolites, before and after treatment in early rheumatoid arthritis patients: a pilot study
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304627/
https://www.ncbi.nlm.nih.gov/pubmed/35872763
http://dx.doi.org/10.3389/fmed.2022.921675
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