Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China.
Appl Microbiol Biotechnol. 2022 Feb;106(4):1615-1631. doi: 10.1007/s00253-022-11813-5. Epub 2022 Feb 7.
Rhubarb, a traditional herb, has been used in clinical practice for hundreds of years to cure constipation, but its mechanism is still not clear enough. Currently, growing evidence suggests that intestinal flora might be a potential target for the treatment of constipation. Thus, the aim of this study was to clarify the laxative effect of rhubarb via systematically analyzing the metagenome and metabolome of the gut microbiota. In this study, the laxative effects of rhubarb were investigated by loperamide-induced constipation in rats. The gut microbiota was determined by high-throughput sequencing of 16S rRNA gene. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for fecal metabolomics analysis. The data showed that rhubarb could significantly shorten gastrointestinal transit time, increase fecal water content and defecation frequency, improve gastrointestinal hormone disruption, and protect the colon mucus layer. Analysis of 16S rRNA gene sequencing indicated that rhubarb could improve the disorder of intestinal microbiota in constipated rats. For example, beneficial bacteria such as Ligilactobacillus, Limosilalactobacillus, and Prevotellaceae UCG-001 were remarkably increased, and pathogens such as Escherichia-Shigella were significantly decreased after rhubarb treatment. Additionally, the fecal metabolic profiles of constipated rats were improved by rhubarb. After rhubarb treatment, metabolites such as chenodeoxycholic acid, cholic acid, prostaglandin F2α, and α-linolenic acid were markedly increased in constipation rats; in contrast, the metabolites such as lithocholic acid, calcidiol, and 10-hydroxystearic acid were notably reduced in constipation rats. Moreover, correlation analysis indicated a close relationship between intestinal flora, fecal metabolites, and biochemical indices associated with constipation. In conclusion, the amelioration of rhubarb in constipation might modulate the intestinal microflora and its metabolism. Moreover, the application of fecal metabolomics could provide a new strategy to uncover the mechanism of herbal medicines.Key points• Rhubarb could significantly improve gut microbiota disorder in constipation rats.• Rhubarb could markedly modulate the fecal metabolite profile of constipated rats.
大黄是一种传统草药，已在临床实践中使用数百年以治疗便秘，但其机制尚不清楚。目前，越来越多的证据表明，肠道菌群可能是治疗便秘的潜在靶点。因此，本研究旨在通过系统分析肠道微生物菌群的宏基因组和代谢组学来阐明大黄的通便作用。在这项研究中，通过洛哌丁胺诱导的大鼠便秘来研究大黄的通便作用。通过 16S rRNA 基因高通量测序来确定肠道微生物菌群。采用超高效液相色谱-四极杆飞行时间质谱法进行粪便代谢组学分析。数据表明，大黄可显著缩短胃肠道转运时间，增加粪便含水量和排便频率，改善胃肠激素紊乱，保护结肠黏液层。16S rRNA 基因测序分析表明，大黄可改善便秘大鼠肠道微生物菌群的紊乱。例如，大黄处理后，有益菌如Ligilactobacillus、Limosilalactobacillus 和 Prevotellaceae UCG-001 显著增加，而大肠杆菌-志贺氏菌等病原体显著减少。此外，大黄还可改善便秘大鼠的粪便代谢谱。大黄处理后，便秘大鼠中胆酸脱氧胆酸、胆酸、前列腺素 F2α 和α-亚麻酸等代谢物明显增加；相反，石胆酸、钙二醇和 10-羟基硬脂酸等代谢物在便秘大鼠中明显减少。此外，相关分析表明，肠道菌群、粪便代谢物与便秘相关的生化指标之间存在密切关系。总之，大黄对便秘的改善可能通过调节肠道微生物菌群及其代谢来实现。此外，粪便代谢组学的应用可以为揭示草药的作用机制提供一种新策略。
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