Zengye decoction plays a key role in treating aged constipation by regulating host gut microbiota and endogenous metabolites.

Zengye decoction (ZYD), a traditional Chinese medicinal formula, has been used in the treatment of various chronic diseases, such as constipation and skin dryness syndrome. Clinically, the specific mechanisms and targets of ZYD for treating disease remain unclear. The present study was undertaken to investigate the effects of ZYD on the gut microbiota and host metabolites in aged constipated rats and the relationship between the intestinal microbiota and the host. Rats were divided randomly into three groups, the control group (n = 10), recovery group (n = 10) and ZYD group (n = 10). First, the aged constipation model was established for the ZYD group and recovery group. Then, rats in the ZYD group were treated with ZYD. Urinary and faecal samples of each animal were collected in microcentrifuge tubes. Next, 16s rRNA gene sequencing was employed to analyse the composition of the gut microbiome in faecal samples and afterwards the metabolic function of the altered gut microbiota was predicted. Additionally, ¹H NMR profiling was used to detect the alterations of host metabolites in urine and faecal samples to verify the metabolic function results obtained from sequencing. As a result, ZYD reduced the level of harmful bacteria, such as Desulfovibrio, Ruminococcus, Prevotella and Dorea, and increased the abundance of Oxalobacter, Clostridium and Roseburia. The functional prediction of changes in the gut microbiota induced by ZYD revealed that ZYD promoted energy storage, regulated amino acid metabolism, inhibited methane metabolism, strengthened the physiological function of glutathione and reduced bacterial toxin. The ¹H NMR profiles revealed that ZYD regulated the carbohydrates, short chain fatty acids, amino acids and amines in the aged constipated rats. In addition, most metabolic changes observed were related to the function of intestinal microbiota. These results suggest that ZYD can regulate the intestinal microbiota of constipated rats to normal levels and change the endogenous metabolites of the host through the intestinal microbiota to achieve therapeutic effects.