Microbiota-derived butyrate dampens linaclotide stimulation of the guanylate cyclase C pathway in patient-derived colonoids.

ABSTRACT:

Background & aims

Disorders of gut-brain interaction (DGBI) are complex conditions that result in decreased quality of life and a significant cost burden. Linaclotide, a guanylin cyclase C (GCC) receptor agonist, is approved as a DGBI treatment. However, its efficacy has been limited and variable across DGBI patients. Microbiota and metabolomic alterations are noted in DGBI patients, provoking the hypothesis that the microbiota may impact the GCC response to current therapeutics.

Methods

Human-derived intestinal organoids were grown from pediatric DGBI, non-IBD colon biopsies (colonoids). Colonoids were treated with 250 nM linaclotide and assayed for cGMP to develop a model of GCC activity. Butyrate was administered to human colonoids overnight at a concentration of 1 mM. Co

SUBMITTER: Velez Lopez A 

PROVIDER: S-EPMC10841278 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature