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

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 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 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.