Zuogui Jiangtang Jieyu prescription improves diabetes-related depression by modulation of gut microbiota and neuroinflammation in hippocampus

Abstract

Context: There is a significant challenge associated with the co-morbidity of mental and physical illnesses throughout the world. A classic example of mental/physical co-morbidity is diabetes-related depression (DD). Objective: DD is treated with Zuogui Jiangtang Jieyu prescription (ZJJ). Diabetes and psychiatric disorders are associated with dysbiosis of the gut microbiota. In this study, the aim is to examine the effects of ZJJ on gut microbiota and neuroinflammation in DD. Methods: A model of DD was established and treated with medium and high doses of ZJJ as well as Metformin & Fluoxetine. A detection of depressive-like behavior was then conducted on the rats. Proinflammatory cytokines were measured in cerebrospinal fluid, and HPA axis-related proteins, glucose metabolism, and lipopolysaccharide (LPS) were measured in serum. Fecal samples from each group were collected and analyzed by 16S rRNA sequencing; TLR4 and MyD88 levels were detected by Western blot and immunohistochemistry (IHC) in the hippocampus. Results: High doses of ZJJ (ZJJ-H) were found to alleviate HPA axis hyperactivity and improve gut microbiota in rats with DD. Additionally, ZJJ treatment attenuated the inflammatory response in cerebrospinal fluid, e.g. a significant reduction in proinflammatory factors, a decrease in serum LPS levels, and an inhibition of TLR4/MyD88-related pathways in the hippocampus. Discussion and conclusion: ZJJ improved DD glucose metabolism and alleviated depression-like behaviors by improving gut microbiota and inhibiting hippocampal TLR4/Myd88 signaling pathways.

Keywords

• Zuogui Jiangtang Jieyu prescription
• Gut microbiota
• 16S rRNA
• Inflammation
• TLR4/MyD88