Cargando…
Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative
Rheumatoid arthritis (RA), an autoimmune disease, is characterized by chronic joint inflammation and pain. We previously found that the deletion of T-cell death-associated gene 8 (TDAG8) significantly reduces disease severity and pain in RA mice. Whether it is by modulating gut microbiota remains un...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998664/ https://www.ncbi.nlm.nih.gov/pubmed/35408888 http://dx.doi.org/10.3390/ijms23073527 |
_version_ | 1784684997508071424 |
---|---|
author | Nguyen, Ngoc Tuan Sun, Wei-Hsin Chen, Tzu-Hsuan Tsai, Po-Chun Chen, Chih-Chen Huang, Shir-Ly |
author_facet | Nguyen, Ngoc Tuan Sun, Wei-Hsin Chen, Tzu-Hsuan Tsai, Po-Chun Chen, Chih-Chen Huang, Shir-Ly |
author_sort | Nguyen, Ngoc Tuan |
collection | PubMed |
description | Rheumatoid arthritis (RA), an autoimmune disease, is characterized by chronic joint inflammation and pain. We previously found that the deletion of T-cell death-associated gene 8 (TDAG8) significantly reduces disease severity and pain in RA mice. Whether it is by modulating gut microbiota remains unclear. In this study, 64 intestinal samples of feces, cecal content, and cecal mucus from the complete Freund’s adjuvant-induced arthritis mouse models were compared. The α- and β-diversity indices of the microbiome were significantly lower in RA mice. Cecal mucus showed a higher ratio of Firmicutes to Bacteroidetes in RA than healthy mice, suggesting the ratio could serve as an RA indicator. Four core genera, Eubacterium_Ventriosum, Alloprevotella, Rikenella, and Treponema, were reduced in content in both feces and mucus RA samples, and could serve microbial markers representing RA progression. TDAG8 deficiency decreased the abundance of proinflammation-related Eubacterium_Xylanophilum, Clostridia, Ruminococcus, Paraprevotella, and Rikenellaceae, which reduced local mucosal inflammation to relieve RA disease severity and pain. The pharmacological block of the TDAG8 function by a salicylanilide derivative partly restored the RA microbiome to a healthy composition. These findings provide a further understanding of specific bacteria interactions with host gut mucus in the RA model. The modulation by TDAG8 on particular bacteria can facilitate microbiota-based therapy. |
format | Online Article Text |
id | pubmed-8998664 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89986642022-04-12 Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative Nguyen, Ngoc Tuan Sun, Wei-Hsin Chen, Tzu-Hsuan Tsai, Po-Chun Chen, Chih-Chen Huang, Shir-Ly Int J Mol Sci Article Rheumatoid arthritis (RA), an autoimmune disease, is characterized by chronic joint inflammation and pain. We previously found that the deletion of T-cell death-associated gene 8 (TDAG8) significantly reduces disease severity and pain in RA mice. Whether it is by modulating gut microbiota remains unclear. In this study, 64 intestinal samples of feces, cecal content, and cecal mucus from the complete Freund’s adjuvant-induced arthritis mouse models were compared. The α- and β-diversity indices of the microbiome were significantly lower in RA mice. Cecal mucus showed a higher ratio of Firmicutes to Bacteroidetes in RA than healthy mice, suggesting the ratio could serve as an RA indicator. Four core genera, Eubacterium_Ventriosum, Alloprevotella, Rikenella, and Treponema, were reduced in content in both feces and mucus RA samples, and could serve microbial markers representing RA progression. TDAG8 deficiency decreased the abundance of proinflammation-related Eubacterium_Xylanophilum, Clostridia, Ruminococcus, Paraprevotella, and Rikenellaceae, which reduced local mucosal inflammation to relieve RA disease severity and pain. The pharmacological block of the TDAG8 function by a salicylanilide derivative partly restored the RA microbiome to a healthy composition. These findings provide a further understanding of specific bacteria interactions with host gut mucus in the RA model. The modulation by TDAG8 on particular bacteria can facilitate microbiota-based therapy. MDPI 2022-03-24 /pmc/articles/PMC8998664/ /pubmed/35408888 http://dx.doi.org/10.3390/ijms23073527 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nguyen, Ngoc Tuan Sun, Wei-Hsin Chen, Tzu-Hsuan Tsai, Po-Chun Chen, Chih-Chen Huang, Shir-Ly Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative |
title | Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative |
title_full | Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative |
title_fullStr | Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative |
title_full_unstemmed | Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative |
title_short | Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative |
title_sort | gut mucosal microbiome is perturbed in rheumatoid arthritis mice and partly restored after tdag8 deficiency or suppression by salicylanilide derivative |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998664/ https://www.ncbi.nlm.nih.gov/pubmed/35408888 http://dx.doi.org/10.3390/ijms23073527 |
work_keys_str_mv | AT nguyenngoctuan gutmucosalmicrobiomeisperturbedinrheumatoidarthritismiceandpartlyrestoredaftertdag8deficiencyorsuppressionbysalicylanilidederivative AT sunweihsin gutmucosalmicrobiomeisperturbedinrheumatoidarthritismiceandpartlyrestoredaftertdag8deficiencyorsuppressionbysalicylanilidederivative AT chentzuhsuan gutmucosalmicrobiomeisperturbedinrheumatoidarthritismiceandpartlyrestoredaftertdag8deficiencyorsuppressionbysalicylanilidederivative AT tsaipochun gutmucosalmicrobiomeisperturbedinrheumatoidarthritismiceandpartlyrestoredaftertdag8deficiencyorsuppressionbysalicylanilidederivative AT chenchihchen gutmucosalmicrobiomeisperturbedinrheumatoidarthritismiceandpartlyrestoredaftertdag8deficiencyorsuppressionbysalicylanilidederivative AT huangshirly gutmucosalmicrobiomeisperturbedinrheumatoidarthritismiceandpartlyrestoredaftertdag8deficiencyorsuppressionbysalicylanilidederivative |