Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease with a complex etiology comprising numerous genetic and environmental factors; however, many of the mechanisms underlying disease development remain unclear. Nevertheless, a critical role has recently been assigned to intestinal microorganisms in T1DM disease pathogenesis. In particular, a decrease in intestinal microbial diversity, increase in intestinal permeability, and the translocation of intestinal bacteria to the pancreas have been reported in patients and animal models with T1DM. Moreover, intestinal microbial metabolites differ between healthy individuals and patients with T1DM. Specifically, short-chain fatty acid (SCFA) production, which contributes to intestinal barrier integrity and immune response regulation, is significantly reduced in patients with T1DM. Considering this correlation between intestinal microorganisms and T1DM, many studies have investigated the potential of intestinal microbiota in preventive and therapeutic strategies for T1DM. Objective: The aim of this review is to provide further support for the notion that intestinal microbiota contributes to the regulation of T1DM occurrence and development. In particular, this article reviews the involvement of the intestinal microbiota and the associated metabolites in T1DM pathogenesis, as well as recent studies on the involvement of the intestinal microbiota in T1DM prevention and treatment. Conclusion:Intestinal microbes and their metabolites contribute to T1DM occurrence and development and may become a potential target for novel therapeutics.

Stem cell engraftment is currently a promising approach for type 1 diabetes mellitus (T1DM) treatment. In our previous study, engraftment of a combination of human amniotic epithelial cells (hAECs) and hyaluronic acid (HA) showed potent anti-diabetic effect in streptozotocin (STZ)-induced T1DM mice via tail vein injection. Here, we adopted a different route of stem cell delivery, that is via pancreatic subcapsular transplantation. This combined local engraftment of hAECs and HA in STZ-induced T1DM rats showed potent anti-diabetic activity, leading to stronger hypoglycaemia, more intact islet structure and increased number of insulin-positive cells compared with those with hAECs or insulin treatments. Engraftment of hAECs alone increased the proportion of Th1 and Treg cells and decreased the proportion of Th2 and Th17 cells to protect islet β cells in STZ-induced T1DM rats, whereas the combined engraftment of hAECs and HA showed more potent regulatory capacity, considerably decreased the level of TNF-α and IL-17 and increased the level of TGF-β1 compared with those by other treatments. The potent synergistic effect of HA contributed to the recovery of immune balance in the diabetic rat model, thereby suggesting a new strategy for effective treatment of T1DM. How to cite this article: Cheng Y-W, Luo Y, Zheng S-J, Xiao J-H. Combination therapy with human amniotic epithelial cells and hyaluronic acid promotes immune balance recovery in type 1 diabetic rats through local engraftment.