Yingjie Guo1, Yanan Yu1, Hailong Li2, Xueli Ding1, Xiaoyu Li1, Xue Jing1, Jianwei Chen3,4, Guilin Liu3, Yuan Lin1, Chen Jiang1, Zhen Liu2, Yuwei He2, Changgui Li5, Zibin Tian6. 1. Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China. 2. Institute of Metabolic Diseases, Qingdao University, Qingdao, 266003, Shandong, China. 3. BGI-Qingdao, BGI-Shenzhen, Qingdao, 266555, Shandong, China. 4. Synthetic Biology Technology Innovation Center of Shandong Province, Qingdao, 266101, Shandong, China. 5. Institute of Metabolic Diseases, Qingdao University, Qingdao, 266003, Shandong, China. lichanggui@medmail.com.cn. 6. Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China. tianzbsun@163.com.
Abstract
PURPOSE: Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. METHODS: KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. RESULTS: Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. CONCLUSIONS: Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.
PURPOSE: Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. METHODS: KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. RESULTS: Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemicmice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. CONCLUSIONS: Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.
Entities:
Keywords:
Gut microbiota; Hyperuricemia; Inflammation; Intestinal barrier; Inulin;; Short chain fatty acids
Authors: Gabriela A Martínez-Nava; Eder O Méndez-Salazar; Janitzia Vázquez-Mellado; Yessica Zamudio-Cuevas; Adriana Francisco-Balderas; Karina Martínez-Flores; Javier Fernández-Torres; Carlos Lozada-Pérez; Dafne L Guido-Gómora; Laura E Martínez-Gómez; Guadalupe E Jiménez-Gutiérrez; Carlos Pineda; Luis H Silveira; Laura Sánchez-Chapul; Roberto Sánchez-Sánchez; María Del Carmen Camacho-Rea; Carlos Martínez-Armenta; Ana I Burguete-García; Citlalli Orbe-Orihuela; Alfredo Lagunas-Martínez; Berenice Palacios-González; Alberto López-Reyes Journal: Clin Rheumatol Date: 2022-10-06 Impact factor: 3.650
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