Study on Sijunzi decoction regulating intestinal microbiota structure and metabolic profile for improving chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a syndrome encompassing several systemic diseases. Sijunzi Decoction (SJZD) is a classic formula in traditional Chinese medicine (TCM) for the treatment of spleen deficiency syndrome. Studies have demonstrated that SJZD can effectively alleviate CFS by modulating the gut microbiota, yet the underlying mechanisms are still unknown. This investigation examined the specific mechanisms by which SJZD regulates intestinal microbiota structure and metabolic profiles to improve CFS. A rat model of CFS triggered by combined multi-factor stress was established, and the rats were treated with SJZD continuously for 30 days. Comprehensive evaluation included body weight, 3-h food intake, intestinal propulsion and gastric emptying rates, exhaustive swimming time, skeletal muscle ATPase content, and indices correlated with oxidative stress and energy metabolism. Serum metabolomics, fecal metabolomics, and 16S rRNA microbial community analysis were applied to investigate the therapeutic mechanism of SJZD in CFS rats. SJZD can improve the general symptoms of CFS rats, as well as the abnormalities of indicators related to oxidative stress and energy metabolism. Metabolomics results showed that SJZD exerted therapeutic effects mainly by regulating 7 fecal differential metabolites and 25 serum differential metabolites. 16S rRNA sequencing analysis illustrated that SJZD elevated the diversity and composition of intestinal microbiota in CFS rats, while decreasing the Firmicutes/Bacteroidetes (F/B) ratio. Moreover, significant relationships were detected between the microbiota and serum/fecal metabolites as well as biochemical indices. SJZD exhibited significant therapeutic effects on CFS rats, and its mechanism may be correlated with regulating the intestinal microbiota structure and metabolic profiles of CFS rats, thereby improving oxidative stress injury and energy metabolism disorders.