Microbial metabolite p-cresol inhibits gut hormone expression and regulates small intestinal transit in mice
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Microbial metabolite p-cresol inhibits gut hormone expression and regulates small intestinal transit in mice. / Toft, Pernille Baumann; Vanslette, Amanda Marie; Trošt, Kajetan; Moritz, Thomas; Gillum, Matthew Paul; Bäckhed, Fredrik; Arora, Tulika.
In: Frontiers in Endocrinology, Vol. 14, 1200391, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Microbial metabolite p-cresol inhibits gut hormone expression and regulates small intestinal transit in mice
AU - Toft, Pernille Baumann
AU - Vanslette, Amanda Marie
AU - Trošt, Kajetan
AU - Moritz, Thomas
AU - Gillum, Matthew Paul
AU - Bäckhed, Fredrik
AU - Arora, Tulika
N1 - Publisher Copyright: Copyright © 2023 Toft, Vanslette, Trošt, Moritz, Gillum, Bäckhed and Arora.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - GLP-1
KW - metabolic disease
KW - microbial metabolite
KW - p-cresol
KW - small intestinal transit
U2 - 10.3389/fendo.2023.1200391
DO - 10.3389/fendo.2023.1200391
M3 - Journal article
C2 - 37534214
AN - SCOPUS:85166435214
VL - 14
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
M1 - 1200391
ER -
ID: 361688945