Butyric Acid Modulates Gut Microbiota to Alleviate Inflammation and Secondary Bone Loss in Ankylosing Spondylitis

<b>Background:</b> Ankylosing spondylitis (AS) is a chronic inflammatory and autoimmune disease that primarily affects the sacroiliac joints and axial skeleton. While the exact pathogenetic mechanism of AS remains unclear, previous reports have highlighted the involvement of genetic fact...

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Main Authors: Ke You, Lianjun Yang, Zhihai Su, Jun Shen, Xinyang Fan, Yuanqing Guo, Zhen Yuan, Hai Lu
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/9
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author Ke You
Lianjun Yang
Zhihai Su
Jun Shen
Xinyang Fan
Yuanqing Guo
Zhen Yuan
Hai Lu
author_facet Ke You
Lianjun Yang
Zhihai Su
Jun Shen
Xinyang Fan
Yuanqing Guo
Zhen Yuan
Hai Lu
author_sort Ke You
collection DOAJ
description <b>Background:</b> Ankylosing spondylitis (AS) is a chronic inflammatory and autoimmune disease that primarily affects the sacroiliac joints and axial skeleton. While the exact pathogenetic mechanism of AS remains unclear, previous reports have highlighted the involvement of genetic factors, immune responses, and gut microbiota dysregulation in the development of this condition. Short-chain fatty acids (SCFAs), which are microbial fermentation products derived from sugar, protein, and dietary fibers, play a role in maintaining the intestinal barrier function and reducing inflammatory responses. The aim of this study was to investigate the therapeutic potential of butyric acid (BA), an important SCFA, in the treatment of AS. <b>Methods:</b> To evaluate the anti-inflammatory and anti-bone loss effects of BA, a murine AS model was established using proteoglycan and dimethyl dioctadecyl ammonium (DDA) adjuvants. Various techniques, including an enzyme-linked immunosorbent assay (ELISA), magnetic resonance imaging (MRI), micro-CT, histology, quantitative PCR (qPCR) for intestinal tight junction protein expression, and 16S rDNA sequencing to analyze gut microbiota abundance, were employed to assess the inflammation and bone health in the target tissues. <b>Results:</b> The results indicated that BA demonstrated potential in alleviating the inflammatory response in the peripheral joints and the axial spine affected by AS, as evidenced by the reductions in inflammatory infiltration, synovial hyperplasia, and endplate erosion. Furthermore, BA was found to impact the intestinal barrier function positively. Notably, BA was associated with the downregulation of harmful inflammatory factors and the reversal of bone loss, suggesting its protective effects against AS. <b>Conclusions:</b> These beneficial effects were attributed to the modulation of gut microbiota, anti-inflammatory properties, and the maintenance of skeletal metabolic homeostasis. This study contributes new evidence supporting the relationship between gut microbiota and bone health.
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spelling doaj-art-be93ca6472654a899fdc748ae110e5b92025-01-24T13:23:42ZengMDPI AGBiomedicines2227-90592024-12-01131910.3390/biomedicines13010009Butyric Acid Modulates Gut Microbiota to Alleviate Inflammation and Secondary Bone Loss in Ankylosing SpondylitisKe You0Lianjun Yang1Zhihai Su2Jun Shen3Xinyang Fan4Yuanqing Guo5Zhen Yuan6Hai Lu7Department of Spine Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519082, ChinaDepartment of Spine Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519082, ChinaDepartment of Spine Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519082, ChinaDepartment of Spine Surgery, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, ChinaCentre of Education Development, South China Normal University, Guangzhou 510006, ChinaDepartment of Spine Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519082, ChinaFaculty of Health Sciences, University of Macau, Macau 999078, ChinaDepartment of Spine Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519082, China<b>Background:</b> Ankylosing spondylitis (AS) is a chronic inflammatory and autoimmune disease that primarily affects the sacroiliac joints and axial skeleton. While the exact pathogenetic mechanism of AS remains unclear, previous reports have highlighted the involvement of genetic factors, immune responses, and gut microbiota dysregulation in the development of this condition. Short-chain fatty acids (SCFAs), which are microbial fermentation products derived from sugar, protein, and dietary fibers, play a role in maintaining the intestinal barrier function and reducing inflammatory responses. The aim of this study was to investigate the therapeutic potential of butyric acid (BA), an important SCFA, in the treatment of AS. <b>Methods:</b> To evaluate the anti-inflammatory and anti-bone loss effects of BA, a murine AS model was established using proteoglycan and dimethyl dioctadecyl ammonium (DDA) adjuvants. Various techniques, including an enzyme-linked immunosorbent assay (ELISA), magnetic resonance imaging (MRI), micro-CT, histology, quantitative PCR (qPCR) for intestinal tight junction protein expression, and 16S rDNA sequencing to analyze gut microbiota abundance, were employed to assess the inflammation and bone health in the target tissues. <b>Results:</b> The results indicated that BA demonstrated potential in alleviating the inflammatory response in the peripheral joints and the axial spine affected by AS, as evidenced by the reductions in inflammatory infiltration, synovial hyperplasia, and endplate erosion. Furthermore, BA was found to impact the intestinal barrier function positively. Notably, BA was associated with the downregulation of harmful inflammatory factors and the reversal of bone loss, suggesting its protective effects against AS. <b>Conclusions:</b> These beneficial effects were attributed to the modulation of gut microbiota, anti-inflammatory properties, and the maintenance of skeletal metabolic homeostasis. This study contributes new evidence supporting the relationship between gut microbiota and bone health.https://www.mdpi.com/2227-9059/13/1/9ankylosing spondylitisgut microbiotashort-chain fatty acidinflammatory responsebone loss
spellingShingle Ke You
Lianjun Yang
Zhihai Su
Jun Shen
Xinyang Fan
Yuanqing Guo
Zhen Yuan
Hai Lu
Butyric Acid Modulates Gut Microbiota to Alleviate Inflammation and Secondary Bone Loss in Ankylosing Spondylitis
Biomedicines
ankylosing spondylitis
gut microbiota
short-chain fatty acid
inflammatory response
bone loss
title Butyric Acid Modulates Gut Microbiota to Alleviate Inflammation and Secondary Bone Loss in Ankylosing Spondylitis
title_full Butyric Acid Modulates Gut Microbiota to Alleviate Inflammation and Secondary Bone Loss in Ankylosing Spondylitis
title_fullStr Butyric Acid Modulates Gut Microbiota to Alleviate Inflammation and Secondary Bone Loss in Ankylosing Spondylitis
title_full_unstemmed Butyric Acid Modulates Gut Microbiota to Alleviate Inflammation and Secondary Bone Loss in Ankylosing Spondylitis
title_short Butyric Acid Modulates Gut Microbiota to Alleviate Inflammation and Secondary Bone Loss in Ankylosing Spondylitis
title_sort butyric acid modulates gut microbiota to alleviate inflammation and secondary bone loss in ankylosing spondylitis
topic ankylosing spondylitis
gut microbiota
short-chain fatty acid
inflammatory response
bone loss
url https://www.mdpi.com/2227-9059/13/1/9
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