"The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study"

作者全名："Zhou, Jianyun; Wei, Haoqi; Zhou, An; Xiao, Xu; Xie, Xia; Tang, Bo; Lin, Hui; Tang, Li; Meng, Ruiping; Yuan, Xiaoying; Zhang, Jing; Huang, Cheng; Huang, Baobao; Liao, Xiping; Zhong, Tingting; He, Suyu; Gu, Sai; Yang, Shiming"

作者地址："[Zhou, Jianyun; Wei, Haoqi; Zhou, An; Xiao, Xu; Xie, Xia; Tang, Bo; Lin, Hui; Tang, Li; Meng, Ruiping; Huang, Baobao; Liao, Xiping; Zhong, Tingting; Yang, Shiming] Third Mil Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Xinqiaozheng St, Chongqing 400037, Peoples R China; [Yuan, Xiaoying] Ninth Peoples Hosp Chongqing, Dept Gastroenterol, 69 Jialing Village, Chongqing 400700, Peoples R China; [Zhang, Jing] Chongqing Univ, Dept Gastroenterol, Jiangjin Hosp, 725 Jiangzhou Ave, Chongqing 402260, Peoples R China; [Huang, Cheng] Chonggang Gen Hosp, Dept Gastroenterol, 1 Dayan Sancun, Chongqing 400000, Peoples R China; [He, Suyu] Suining Cent Hosp, Dept Gastroenterol, 22 Youfang St, Suining 629000, Peoples R China; [Gu, Sai] Chongqing Med Univ Jinshan Campus, Dept Gastroenterol, Affiliated Hosp 1, 50 Jinyu Dadao, Chongqing 401112, Peoples R China"

通信作者："Yang, SM (通讯作者)，Third Mil Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Xinqiaozheng St, Chongqing 400037, Peoples R China.; He, SY (通讯作者)，Suining Cent Hosp, Dept Gastroenterol, 22 Youfang St, Suining 629000, Peoples R China.; Gu, S (通讯作者)，Chongqing Med Univ Jinshan Campus, Dept Gastroenterol, Affiliated Hosp 1, 50 Jinyu Dadao, Chongqing 401112, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001148364300003

JCR分区：Q1

影响因子：7.4

年份：2024

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：IBS-C; Linaclotide; Gut microbiome; Blautia; SCFAs

摘要："Background Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy.Methods IBS-C patients were administered a daily linaclotide dose of 290 mu g over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations.Results Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients.Conclusion The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment."

基金机构：Chongqing Science and Technology Foundation

基金资助正文：We would like to additionally thank Xin Xiong and Jinneng Wang for helping with the sample collection and Yuanyuan Lei and Dianji Tu for their expertise and help with the 16S sequencing experiments. We are also grateful for all the patients who participated in the study. None of the patients received any compensation.