Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolism

BackgroundRheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Numerous clinical studies have indicated a correlation between alterations in gut microbiota and the onset and progression of RA. This research aims to restore intestinal microbiota to a healthy state through th...

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Main Authors: Yang Yang, Qing Hong, Xuehong Zhang, Zhenmin Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1518181/full
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author Yang Yang
Yang Yang
Qing Hong
Qing Hong
Xuehong Zhang
Zhenmin Liu
Zhenmin Liu
author_facet Yang Yang
Yang Yang
Qing Hong
Qing Hong
Xuehong Zhang
Zhenmin Liu
Zhenmin Liu
author_sort Yang Yang
collection DOAJ
description BackgroundRheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Numerous clinical studies have indicated a correlation between alterations in gut microbiota and the onset and progression of RA. This research aims to restore intestinal microbiota to a healthy state through the oral administration of Bifidobacterium in the early stages with the goal of delaying the onset and progression of RA.MethodsCollagen-induced arthritis (CIA) rat model was constructed to assess the development of RA using arthritis clinical scores, paw thickness, pathological analysis of knee joint. The immune response was evaluated by determinating specific antibodies and cytokines in serum and synovial fluid. The expression of intestinal barrier protein was analyzed by qPCR to evaluate the intestinal barrier function. Alterations in gut microbiota and metabolites were assessed by 16S rDNA and non-targeted metabolomics.ResultsThe findings reveal that administering Bifidobacterium animalis BD400 orally led to a significant reduction in arthritis clinical scores and paw swelling thickness in CIA rats. Additionally, there was a decrease in osteo-facial fusion and calcified cartilage thickening in the knee joint. Furthermore, the oral administration of B. animalis BD400 resulted in the down-regulation of inflammatory factors TNF-α and collagenase MMP-13 in the knee joint. Levels of specific antibodies (anti-CII IgG, anti-CII IgG1, and anti-CII IgG2a) and cytokine IL-17A in serum, as well as cytokines (TNF-α and IL-1β) in the synovial fluid of B. animalis BD400-treated CIA rats, were significantly reduced (p < 0.05). The gene expression levels of intestinal barrier proteins (occludin-1, MUC-2, and ZO-1) showed a significant increase (p < 0.05) in B. animalis BD400-treated CIA rats. The oral administration of B. animalis BD400 altered the composition of intestinal microorganisms in CIA rats at the phylum and genus levels, particularly affecting the genus HT002. B. animalis BD400 alleviates RA by down-regulating 1-methyl-L-histidine and urocanate in the histidine metabolism, laying a foundation for the RA prevention.ConclusionBy affecting genus HT002 and histidine metabolism in the gut microbiota of CIA rats, B. animalis BD400 restored intestinal permeability, inhibited systemic inflammatory response, and ultimately slowed down the development of RA.
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spelling doaj-art-edf16201a34d403081d5a8190e52b1ce2025-01-22T07:13:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15181811518181Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolismYang Yang0Yang Yang1Qing Hong2Qing Hong3Xuehong Zhang4Zhenmin Liu5Zhenmin Liu6State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Shanghai, ChinaDairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Shanghai, ChinaDairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaState Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Shanghai, ChinaDairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, ChinaBackgroundRheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Numerous clinical studies have indicated a correlation between alterations in gut microbiota and the onset and progression of RA. This research aims to restore intestinal microbiota to a healthy state through the oral administration of Bifidobacterium in the early stages with the goal of delaying the onset and progression of RA.MethodsCollagen-induced arthritis (CIA) rat model was constructed to assess the development of RA using arthritis clinical scores, paw thickness, pathological analysis of knee joint. The immune response was evaluated by determinating specific antibodies and cytokines in serum and synovial fluid. The expression of intestinal barrier protein was analyzed by qPCR to evaluate the intestinal barrier function. Alterations in gut microbiota and metabolites were assessed by 16S rDNA and non-targeted metabolomics.ResultsThe findings reveal that administering Bifidobacterium animalis BD400 orally led to a significant reduction in arthritis clinical scores and paw swelling thickness in CIA rats. Additionally, there was a decrease in osteo-facial fusion and calcified cartilage thickening in the knee joint. Furthermore, the oral administration of B. animalis BD400 resulted in the down-regulation of inflammatory factors TNF-α and collagenase MMP-13 in the knee joint. Levels of specific antibodies (anti-CII IgG, anti-CII IgG1, and anti-CII IgG2a) and cytokine IL-17A in serum, as well as cytokines (TNF-α and IL-1β) in the synovial fluid of B. animalis BD400-treated CIA rats, were significantly reduced (p < 0.05). The gene expression levels of intestinal barrier proteins (occludin-1, MUC-2, and ZO-1) showed a significant increase (p < 0.05) in B. animalis BD400-treated CIA rats. The oral administration of B. animalis BD400 altered the composition of intestinal microorganisms in CIA rats at the phylum and genus levels, particularly affecting the genus HT002. B. animalis BD400 alleviates RA by down-regulating 1-methyl-L-histidine and urocanate in the histidine metabolism, laying a foundation for the RA prevention.ConclusionBy affecting genus HT002 and histidine metabolism in the gut microbiota of CIA rats, B. animalis BD400 restored intestinal permeability, inhibited systemic inflammatory response, and ultimately slowed down the development of RA.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1518181/fullrheumatoid arthritisBifidobacteriumgut microbiotametabolomicsearly intervention
spellingShingle Yang Yang
Yang Yang
Qing Hong
Qing Hong
Xuehong Zhang
Zhenmin Liu
Zhenmin Liu
Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolism
Frontiers in Immunology
rheumatoid arthritis
Bifidobacterium
gut microbiota
metabolomics
early intervention
title Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolism
title_full Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolism
title_fullStr Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolism
title_full_unstemmed Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolism
title_short Bifidobacterium animalis BD400 protects from collagen-induced arthritis through histidine metabolism
title_sort bifidobacterium animalis bd400 protects from collagen induced arthritis through histidine metabolism
topic rheumatoid arthritis
Bifidobacterium
gut microbiota
metabolomics
early intervention
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1518181/full
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