Effect of fecal microbiota transplantation on diabetic wound healing through the IL-17A-mTOR-HIF1α signaling axis.

Abstract

Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a "virtual organ" can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A-mTOR-HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A-mTOR-HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.

Importance: The Intestinal microbiota, as the organ with the largest number of microorganisms in the body, plays a crucial role in the physiological functions of the human body. Normal microbiota can be involved in various functions such as energy absorption, metabolism, and immunity of the body, and microbiota imbalance is related to many diseases such as obesity and diabetes. Diabetes, as one of the world's three major chronic diseases, is a significant health issue that troubles more than a billion people globally. Diabetic wounds are a problem that all diabetic patients must confront when undergoing surgery, and it is an important cause of non-traumatic amputations. Exploring the role of intestinal microorganisms in the wound-healing process of diabetic mice can offer the possibility of using microorganisms as a therapeutic means to intervene in clinically related diseases.