TWK10 relieves loperamide-induced constipation in rats fed a high-fat diet modulating enteric neurotransmitters, short-chain fatty acids and gut microbiota.

Obesity and constipation can alter the intestinal microbiota composition, affecting intestinal barrier integrity, immune function, and metabolic processes. Numerous studies have suggested that and could increase short-chain fatty acid (SCFA) production, thus improving the intestinal microbiota composition, mitigating obesity, and protecting the gastrointestinal tract. Therefore, in this study, we aimed to investigate the impact of TWK10 (TWK10) on gut dysbiosis, obesity, and constipation induced by a high-fat diet and loperamide. Over a 5-week experimental period, rats were fed a high-fat diet and subsequently induced with gut dysbiosis and constipation using loperamide. Concurrently, rats were administered different doses of TWK10 or TWK10-fermented soy milk. Following administration of TWK10 or its fermented soy milk, the expression of adipocyte transcription factors such as PPARγ, C/EBPα, and C/EBPβ proteins and adipocyte size were significantly downregulated ( < 0.05). Regarding intestinal motility, compared to the high-fat diet-induced obesity and loperamide-induced constipation group (L), rats receiving TWK10 or its fermented soy milk exhibited regulation of gastrointestinal hormone levels such as gastrin (GT), somatostatin (Sst), calcitonin gene-related peptide (CGRP), and acetylcholinesterase (Ache) in serum. Additionally, there was a notable increase in the intestinal transit ratio, particularly in the 1X TWK10 group, in which it increased by 10.29% ( < 0.05). Furthermore, the consumption of TWK10 or its fermented soy milk significantly increased the number of goblet cells, as well as the thickness of the muscle and mucosal layers in the colon ( < 0.05). Analysis of SCFA content in fecal samples revealed a significant increase in SCFA concentrations, particularly acetic acid, following administration of both TWK10 and its fermented soy milk. Finally, TWK10 was found to modulate the composition of the intestinal microbiota and increase microbial diversity. In conclusion, TWK10 and its fermented soy milk effectively alleviated loperamide-induced constipation in rats fed a high-fat diet. These findings suggest that TWK10 and its fermented soy milk may potentially be functional foods for promoting intestinal health.