Effect of modified Zengye decoction on age-related constipation via modulation of the host-microbial metabolic axis

Constipation is a common digestive disorder in the elderly caused by weakened intestinal peristalsis and reduced mucus secretion that significantly impacts quality of life. Current treatments typically provide only temporary symptomatic relief and may lead to dependence and adverse effects.

This study investigated the therapeutic effects of a modified traditional Chinese formula, modified Zengye decoction (MZD) on age-related constipation by modulating the gut microbiome and metabolomics. Aged constipated rats were gavage-fed with or without MZD. After detection of the indicators related to the disease, the microbial and metabolic profiles were generated for all the fecal samples by using 16S rRNA gene sequencing and ¹H nuclear magnetic resonance (¹H NMR) spectroscopy, respectively.

MZD effectively alleviated constipation symptoms in aged mice by enhancing the intestinal peristalsis and antioxidant capacity. Gut microbiome analysis revealed that MZD significantly altered the abundance of Firmicutes, Bacteroidetes, and Actinobacteria. Specifically, the abundance of beneficial bacteria such as Corynebacterium, Roseburia, and Clostridium increased by 6-fold, 4-fold, and 3-fold, respectively. These changes in microbial composition enhanced the production of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. Additionally, MZD significantly increased the expression of Mucin 2 protein and the moisture content of the small intestine, while decreasing pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and increasing anti-inflammatory interleukin-10, which may be attributed to the elevated levels of SCFAs.

By effectively regulating the gut microbiome and SCFA metabolism, MZD demonstrated significant anti-inflammatory and mucus-secretion-promoting effects, showing therapeutic potential for age-related constipation, enteritis, and other inflammation-related intestinal diseases.