Microbial metabolite p-cresol inhibits gut hormone expression and regulates small intestinal transit in mice

Pernille Baumann Toft, Amanda Marie Vanslette, Kajetan Trošt, Thomas Moritz, Matthew Paul Gillum, Fredrik Bäckhed, Tulika Arora*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

6 Citations (Scopus)
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Abstract

p-cresol is a metabolite produced by microbial metabolism of aromatic amino acid tyrosine. p-cresol and its conjugated forms, p-cresyl sulfate and p-cresyl glucuronide, are uremic toxins that correlate positively with chronic kidney disease and diabetes pathogenesis. However, how p-cresol affects gut hormones is unclear. Here, we expose immortalized GLUTag cells to increasing concentrations of p-cresol and found that p-cresol inhibited Gcg expression and reduced glucagon-like peptide-1 (GLP-1) secretion in vitro. In mice, administration of p-cresol in the drinking water for 2 weeks reduced the transcript levels of Gcg and other gut hormones in the colon; however, it did not affect either fasting or glucose-induced plasma GLP-1 levels. Furthermore, it did not affect glucose tolerance but promoted faster small intestinal transit in mice. Overall, our data suggest that microbial metabolite p-cresol suppresses transcript levels of gut hormones and regulates small intestinal transit in mice.

Original languageEnglish
Article number1200391
JournalFrontiers in Endocrinology
Volume14
Number of pages7
ISSN1664-2392
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 Toft, Vanslette, Trošt, Moritz, Gillum, Bäckhed and Arora.

Keywords

  • GLP-1
  • metabolic disease
  • microbial metabolite
  • p-cresol
  • small intestinal transit

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