L-Histidine alleviates tacrolimus-induced islet dysfunction via the gut-pancreas axis.

Authors

Zhen Geng, Qiang Li, Duo Wang, Hongji Yang, Hailian Wang, Jinku Bao, Yi Wang, Liang Wei

Published in

iScience. Volume 29. Issue 11. Pages 117802. Nov 20, 2026. Epub Oct 09, 2026.

Abstract

Tacrolimus is widely used after organ transplantation but can impair pancreatic β-cell function and glucose homeostasis. Using rodent models, antibiotic-mediated microbiota depletion, fecal microbiota transplantation, 16S rRNA sequencing, metabolomic profiling, and MIN-6 cells, we examined whether microbiota-associated L-histidine contributes to β-cell protection. Tacrolimus altered gut microbial composition and increased histidine-associated microbial and metabolic signals. L-histidine supplementation improved glucose tolerance and insulin secretion, reduced β-cell apoptosis, and increased PI3K/Akt/mTOR/p70S6K signaling and PDX-1, NeuroD1, and MafA expression. Microbiota depletion attenuated several protective effects of L-histidine, supporting a contribution of the gut microbiota to this response. These findings connect a microbiota-associated amino acid with tacrolimus-related β-cell dysfunction and provide a framework for investigating microbiota-metabolite contributions to metabolic complications of immunosuppression.

PMID:
42894858
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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