Chaihushugan powder regulates the gut microbiota to alleviate mitochondrial oxidative stress in the gastric tissues of rats with functional dyspepsia

Xuejiao Liu ¹ Keming Yang ² Yuebo Jia ¹ Yeliya Yeertai ¹ Chenheng Wu ¹ Xiangxiang Wang ³ Qingling Jia ¹ Zhijian Gu ¹ Jun Cong ¹ Jianghong Ling ^1*

• ¹ Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Beijing Municipality, China
• ² Shenzhen Traditional Chinese Medicine Hospital, Shenzhen ，Guangdong, China
• ³ School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Municipality, China

Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanismis not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.The FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGPtreated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion.Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.The CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP.However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.Chaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.