Distinct effects of TU-100 (daikenchuto) on long-lasting dysbiosis in the small intestine in patients with colorectal cancer and inflammatory bowel disease.

The profile of the human small intestinal microbiota remains to be uncovered primarily due to sampling difficulties. Ileostomy provides the intestinal luminal contents as ileostomy effluents (IE) that offer opportunity for performing extensive analyses of nutrients, gastrointestinal fluids, metabolites, and microbiome. In the present study, we evaluated changes in the microbiome, pH, and bacterial short-chain fatty acids (SCFAs) in IE obtained from patients who had undergone ileostomy following surgical resection of colon cancer and inflammatory bowel disease (IBD). We enrolled 11 patients who varied in the duration of ileostomy from 3 days to >5 years after surgery and had no inflammation in the small intestine. The analyses suggested that IE from patients previously having IBD had less diversity and greater intraday and interday fluctuations, and increased pH and decreased levels of propionic acid and acetic acid than those in IE from patients previously having cancer. Furthermore, correlation analysis suggested a possible effect of the intestinal microbiome on luminal pH, presumably via SCFA production. The present study suggested that inflammation in the colon may induce long-term dysbiosis in the small intestine even after removal of diseased parts of the colon. Moreover, pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) was found to have beneficial effects on postoperative bowel dysfunction and the human small intestinal microbiota. Taken together, these results suggest the necessity of a direct remedy for dysbiosis and the treatment of gastrointestinal lesions to achieve favorable outcomes for chronic gastrointestinal disorders.

Polaprezinc prevents ongoing thioacetamide-induced liver fibrosis in rats.

AIMS: Cirrhotic patients commonly have a liver zinc deficiency, which may aggravate liver fibrosis due to the lack of antioxidative effects of zinc. This study examined the ability of polaprezinc, N-(3-aminopropionyl)-l-histidinato zinc, to prevent fibrosis in a rat model of thioacetamide (TAA)-induced hepatic fibrosis. MAIN METHODS: Liver cirrhosis was induced by orally administering TAA for 20 weeks. The rats were cotreated with one of the following for the last 10 weeks of TAA treatment: (1) polaprezinc (50 or 200mg/kg/day); (2) l-carnosine (155 mg/kg/day), which contained equal amounts of l-carnosine as 200mg/kg/day polaprezinc; (3) zinc sulfate (112 mg/kg/day) or (4) zinc-l-aspartic complex (317.8 mg/kg/day). Both zinc supplementations contained equal amounts of zinc as high-dose polaprezinc. KEY FINDINGS: Hepatic zinc levels fell significantly in rats treated with TAA for 20 weeks. Cotreating with high-dose polaprezinc and zinc-l-aspartic complex for 10 weeks prevented hepatic zinc loss. Hepatic hydroxyproline and tissue inhibitor of metalloproteinases-1 (TIMP-1) were significantly higher in rats treated with TAA for 20 weeks than 10 weeks, whereas polaprezinc prevented changes in these fibrosis markers and reduced hepatic transforming growth factor-ß1 protein concentration, macroscopic and histologic changes. TAA caused oxidative stress-related changes in the liver that were prevented by high-dose polaprezinc and partially by zinc-l-aspartic complex. Treatment with l-carnosine, low-dose polaprezinc or zinc sulfate for 10 weeks did not affect liver fibrosis progression or oxidative stress-related changes. SIGNIFICANCE: Polaprezinc may prevent ongoing fibrosis by preventing zinc depletion, oxidative stress and fibrosis markers in cirrhotic livers.