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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.
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.
Afiliação
  • Zhou J; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Wei H; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Zhou A; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Xiao X; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Xie X; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Tang B; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Lin H; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Tang L; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Meng R; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Yuan X; Department of Gastroenterology, The Ninth People's Hospital of Chongqing, No. 69 Jialing Village, Beibei District, Chongqing, China, 400700.
  • Zhang J; Department of Gastroenterology, Chongqing University Jiangjin Hospital, No.725, Jiangzhou Avenue, Jiangjin District, Chongqing, China, 402260.
  • Huang C; Department of Gastroenterology, Chonggang General Hospital, No. 1 Dayan Sancun, Dadukou District, Chongqing, China, 400000.
  • Huang B; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Liao X; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • Zhong T; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037.
  • He S; Department of Gastroenterology, Suining Central Hospital, 22 Youfang Street, Chuanshan District, Suining, China, 629000. hesuyu2009@163.com.
  • Gu S; Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University Jinshan Campus, 50 Jinyu Dadao, Liangjiang New District, Chongqing, China, 401112. 1601792466@qq.com.
  • Yang S; Department of Gastroenterology, The Second Affiliated Hospital, The Third Military Medical University, Xinqiaozheng Street, Chongqing, China, 400037. 13228686589@163.com.
J Transl Med ; 22(1): 98, 2024 01 23.
Article em En | MEDLINE | ID: mdl-38263117
ABSTRACT

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 µg 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. TRIAL REGISTRATION This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos / Síndrome do Intestino Irritável / Microbioma Gastrointestinal Tipo de estudo: Clinical_trials / Observational_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Transl Med Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos / Síndrome do Intestino Irritável / Microbioma Gastrointestinal Tipo de estudo: Clinical_trials / Observational_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Transl Med Ano de publicação: 2024 Tipo de documento: Article