@article{Chang2026, 
author = {Kunlin Chang and Yifan Feng and Junfeng Dong and Xiaoyu Mou and Yuanzhen Hao and Duowen He and Yayu Zhang and Xiangru Feng and Xiaoxuan Lu and Yijia Chen and Mengyao Zhao and Jiayang Jin and Xiaoguo Ji and Shengxian Li and Hao Yin and Liming Zhao},
title = {Microbiota-Targeted Intervention in Pancreatic Islet Transplant Recipients: Remodeling Glucose-Metabolism Related Microbial Communities Restores Gut Microbiota Balance and Glucose Stability in Type 2 Diabetes},
year = {2026},
journal = {Food Science and Human Wellness},
keywords = {Islet cell transplantation, Islet function, Gut microbiota, Gut barrier, Gut metabolites},
url = {https://www.sciopen.com/article/10.26599/FSHW.2026.9251109},
doi = {10.26599/FSHW.2026.9251109},
abstract = {Islet cell transplantation (ICT) effectively treats type 2 diabetes mellitus (T2DM), but the use of adjunct immunosuppressants/antibiotics disrupts gut microbiota, thereby impairing glucose homeostasis. This study revealed how ICT-induced dysbiosis in functional microbes modulates islet function and glucose metabolism. T2DM patients exhibited marked gut microbiota dysbiosis after ICT, characterized by a significant enrichment of pro-inflammatory microbiota such as Streptococcus and Enterococcus. Conversely, glucose metabolism-related commensals, including Akkermansia, Faecalibacterium, Bacteroides, Fusobacterium, and Bifidobacterium, were significantly reduced. Using a humanized gut microbiota-associated T2DM-ICT mouse model (HMA-T2DM-ICT), intervention with the defined MicroAFB consortium (Akkermansia, Faecalibacterium, Bacteroides) was tested. MicroAFB intervention significantly improved postoperative antibiotic/medication-induced deficiencies in insulin (INS) and C-peptide (C-P) secretion and elevated glycated hemoglobin (HbA1c). It also significantly reduced serum levels of inflammation markers (IP-10, MCP-1) and upregulated intestinal barrier tight junction proteins (MUC2, Occludin, ZO-1). Importantly, microbiota-derived metabolites (bile acids, vitamins B/K) were not only involved in the improvement of glucose homeostasis but also significantly correlated with key biomarkers, including INS, C-P, HbA1c, and GLP-1. Mechanistically, MicroAFB activated insulin signaling via the IRS/PI3K/AKT and GSK-3β/FOXO1 pathways and regulated metabolites such as bile acids and B vitamins/vitamin K, thus suppressing gluconeogenesis and ultimately enhancing insulin sensitivity and glucose homeostasis. The gut microbiota-derived bile acid 3-sulfodeoxycholic acid restored host homeostasis by rebalancing the gut microbiota and activating the TGR5 receptor and its downstream PI3K/AKT/GSK3β pathway. This work pioneered microbial consortium therapy to rectify post-ICT dysbiosis, directly linking microbiota restoration to improved islet function for durable diabetes remission.}
}