Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets

Abstract

Type 2 diabetes is a common metabolic disorder related to insulin resistance, or deficiency of insulin secretion, caused by decreased insulin sensitivity and destruction of islet structure and function. As the second human genome, the microbiota has been observed to have a growing relationship with diabetes in recent years. Microbiota imbalance has been hypothesized to be involved in the regulation of energy metabolism and the inflammatory immune response in diabetes. The present study aimed to investigate whether fecal microbiota transplantation (FMT) could alleviate the symptoms associated with type 2 diabetes. To this end, a type 2 diabetes mouse model was first established through the consumption of a high-fat diet combined with streptozotocin (100 mg/kg), and FMT was used to rebuild the gut microbiota of diabetic mice. Fasting blood glucose, oral glucose tolerance tests, and HbA1c levels were monitored, while the hypoglycemic effects of FMT were also observed. Insulin levels were tested by ELISA and related indexes such as HOMA-IR, HOMA-IS, and HOMA-β were calculated. We found that insulin resistance and pancreatic islet β-cells were improved after FMT treatment. Meanwhile, the markers of inflammation in the pancreatic tissue were detected by ELISA and immunohistochemistry, which indicated that inflammatory response decreased following FMT treatment. Furthermore, flow cytometry and western blot results revealed that FMT inhibited the β-cell apoptosis. Here, the effect of FMT on hypoglycemia in type 2 diabetes was addressed by improving insulin resistance and repairing impaired islets, thereby providing a potential treatment strategy for type 2 diabetes.

Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice

“…S2B). However, in our model and as published by many authors (38)(39)(40), fasting glucose was slightly lower after FMT in comparison to sham FMT, but significantly lower when compared to WD-fed, antibiotics-treated, S-gavaged mice that did not receive DS (two-way ANOVA showed a main effect of FMT gavage # P = 0.0042; Sidak post hoc, *P = 0.04) (SI Appendix, Fig. S2C).…”

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

“…FMT seems to improve disease outcomes through alteration of physiological parameters such as inflammation and gut dysbiosis. For instance, in an STZ‐HFD mouse model of T2DM, fecal transplantation from healthy donor mice ameliorated hyperglycemia, insulin resistance, inflammation, and also improved pancreatic beta‐cell function via inhibition of apoptosis (Wang, Lu, et al., 2020). In another study, FMT from NLRP3 knockout mice resulted in the suppression of astrocyte dysfunction and depressive behavior which had been induced by chronic stress.…”

Microbiota-Mitochondria Inter-Talk: A Potential Therapeutic Strategy in Obesity and Type 2 Diabetes

“…Growing evidence suggests that fecal microbiota transplantation (FMT) is a valuable and promising therapeutic option for diabetes and obesity disorders [131]. FMT showed beneficial effects by attenuating the pancreatic islet β-cell destruction and improving the insulin resistance in T2D patients [131,132], as well as reducing the low-grade chronic inflammation caused by a microbiota imbalance [131].…”

“…Growing evidence suggests that fecal microbiota transplantation (FMT) is a valuable and promising therapeutic option for diabetes and obesity disorders [ 131 ]. FMT showed beneficial effects by attenuating the pancreatic islet β-cell destruction and improving the insulin resistance in T2D patients [ 131 , 132 ], as well as reducing the low-grade chronic inflammation caused by a microbiota imbalance [ 131 ]. Moreover, a recent study by Who et al showed that altered gut microbiota mediates some of the antidiabetic effects of metformin, a drug widely used in T2D that inhibits complex I and enhances the ADP:ATP ratio, thereby activating liver AMPK to slow liver gluconeogenesis [ 133 ].…”