Multiple Low-Dose Radiation ameliorates type-2 diabetes mellitus via gut microbiota modulation to activate TLR4/MyD88/NF-κB pathway

Background Type 2 diabetes mellitus (T2DM) is the fastest-growing metabolic disease in the world. The gut microbiota is linked to the T2DM. Recent studies have showed that the metabolism of gut microbiota can trigger T2DM. Low dose Radiation (LDR) has been proved to activate various protective bioeffects on diabetes. However, the underlying mechanisms remain unclear. Method In this study, T2DM mouse model was established using high fat diet combined with streptozocin (STZ) injection, and then exposed to multiple 75 mGy LDR every other day for one month. The changes of blood glucose levels, body weight, organ weight and damage of pancreas were measured. In addition, 16S rDNA amplicon sequencing was used to detect gut microbiota alteration. Metabolic profiling was carried out using liquid mass spectrometry system, followed by the combinative analysis of gut microbiota alteration. Furthermore, inflammatory factors and related pathways were detected. Results We found that LDR attenuate blood glucose level and weight of body, pancreas, brain, liver and testis in T2DM mice, and reduce pancreas impairment. In addition, in the gut, LDR regulated the relative abundance of bacilli, desulfobacterota, verrucomicrobiota and proteobacteria. The non-target metabolomics analysis found that LDR significantly improve the metabolic abnormalities in T2DM, which is closely related to the gut microbiota abundance. Furthermore, the inflammatory effects activated by TLR4/MyD88/NF-κB pathways in T2DM were ameliorated by LDR. Conclussion : These results suggest that LDR may exert a beneficial role in T2DM by modulating gut microbiota and metabolites, especially in TLR4/MyD88/NF-κB pathway.