Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels

The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from...

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Autores principales: Yunju Jeong, JooYeon Jhun, Seon-Yeong Lee, Hyun Sik Na, JeongWon Choi, Keun-Hyung Cho, Seung Yoon Lee, A Ram Lee, Sang-Jun Park, Hyun Ju You, Ji-Won Kim, Myeong Soo Park, Bin Kwon, Mi-La Cho, Geun Eog Ji, Sung-Hwan Park
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:2b4862f98fe14966a0baf2cc49aae2db2021-11-15T11:25:19ZTherapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels1664-322410.3389/fimmu.2021.736196https://doaj.org/article/2b4862f98fe14966a0baf2cc49aae2db2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.736196/fullhttps://doaj.org/toc/1664-3224The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes—IL-17A, IRF4, RORC, IL-21, and IL-23R—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.Yunju JeongYunju JeongJooYeon JhunJooYeon JhunJooYeon JhunSeon-Yeong LeeSeon-Yeong LeeHyun Sik NaHyun Sik NaHyun Sik NaJeongWon ChoiJeongWon ChoiKeun-Hyung ChoKeun-Hyung ChoKeun-Hyung ChoSeung Yoon LeeSeung Yoon LeeSeung Yoon LeeA Ram LeeA Ram LeeA Ram LeeSang-Jun ParkHyun Ju YouHyun Ju YouJi-Won KimMyeong Soo ParkBin KwonMi-La ChoMi-La ChoMi-La ChoGeun Eog JiGeun Eog JiSung-Hwan ParkFrontiers Media S.A.articlerheumatoid arthritisrheumatoid factormicrobiomeBifidobacterium longumT helper 17 cellImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic rheumatoid arthritis
rheumatoid factor
microbiome
Bifidobacterium longum
T helper 17 cell
Immunologic diseases. Allergy
RC581-607
spellingShingle rheumatoid arthritis
rheumatoid factor
microbiome
Bifidobacterium longum
T helper 17 cell
Immunologic diseases. Allergy
RC581-607
Yunju Jeong
Yunju Jeong
JooYeon Jhun
JooYeon Jhun
JooYeon Jhun
Seon-Yeong Lee
Seon-Yeong Lee
Hyun Sik Na
Hyun Sik Na
Hyun Sik Na
JeongWon Choi
JeongWon Choi
Keun-Hyung Cho
Keun-Hyung Cho
Keun-Hyung Cho
Seung Yoon Lee
Seung Yoon Lee
Seung Yoon Lee
A Ram Lee
A Ram Lee
A Ram Lee
Sang-Jun Park
Hyun Ju You
Hyun Ju You
Ji-Won Kim
Myeong Soo Park
Bin Kwon
Mi-La Cho
Mi-La Cho
Mi-La Cho
Geun Eog Ji
Geun Eog Ji
Sung-Hwan Park
Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels
description The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes—IL-17A, IRF4, RORC, IL-21, and IL-23R—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.
format article
author Yunju Jeong
Yunju Jeong
JooYeon Jhun
JooYeon Jhun
JooYeon Jhun
Seon-Yeong Lee
Seon-Yeong Lee
Hyun Sik Na
Hyun Sik Na
Hyun Sik Na
JeongWon Choi
JeongWon Choi
Keun-Hyung Cho
Keun-Hyung Cho
Keun-Hyung Cho
Seung Yoon Lee
Seung Yoon Lee
Seung Yoon Lee
A Ram Lee
A Ram Lee
A Ram Lee
Sang-Jun Park
Hyun Ju You
Hyun Ju You
Ji-Won Kim
Myeong Soo Park
Bin Kwon
Mi-La Cho
Mi-La Cho
Mi-La Cho
Geun Eog Ji
Geun Eog Ji
Sung-Hwan Park
author_facet Yunju Jeong
Yunju Jeong
JooYeon Jhun
JooYeon Jhun
JooYeon Jhun
Seon-Yeong Lee
Seon-Yeong Lee
Hyun Sik Na
Hyun Sik Na
Hyun Sik Na
JeongWon Choi
JeongWon Choi
Keun-Hyung Cho
Keun-Hyung Cho
Keun-Hyung Cho
Seung Yoon Lee
Seung Yoon Lee
Seung Yoon Lee
A Ram Lee
A Ram Lee
A Ram Lee
Sang-Jun Park
Hyun Ju You
Hyun Ju You
Ji-Won Kim
Myeong Soo Park
Bin Kwon
Mi-La Cho
Mi-La Cho
Mi-La Cho
Geun Eog Ji
Geun Eog Ji
Sung-Hwan Park
author_sort Yunju Jeong
title Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels
title_short Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels
title_full Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels
title_fullStr Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels
title_full_unstemmed Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels
title_sort therapeutic potential of a novel bifidobacterium identified through microbiome profiling of ra patients with different rf levels
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/2b4862f98fe14966a0baf2cc49aae2db
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