L-Histidine alleviates tacrolimus-induced islet dysfunction via the gut-pancreas axis
Year: 2026
Type: article
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.
Source: iScience
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,240
Funders: National Natural Science Foundation of China, Sichuan University, National Science and Technology Major Project, Sichuan Province Science and Technology Support Program, National Key Research and Development Program of China, National Major Science and Technology Projects of China, Chengdu Science and Technology Program
OpenAlex ID: W7221131968