Bofutsushosan improves gut barrier function with a bloom of Akkermansia muciniphila and improves glucose metabolism in mice with diet-induced obesity

• Published in: Scientific reports Vol. 10; no. 1; p. 5544
• Main Authors: Fujisaka, Shiho, Usui, Isao, Nawaz, Allah, Igarashi, Yoshiko, Okabe, Keisuke, Furusawa, Yukihiro, Watanabe, Shiro, Yamamoto, Seiji, Sasahara, Masakiyo, Watanabe, Yoshiyuki, Nagai, Yoshinori, Yagi, Kunimasa, Nakagawa, Takashi, Tobe, Kazuyuki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.03.2020; Nature Publishing Group
• Subjects: 38/91; 631/443/319/1642/393; 64/60; 692/163/2743/393; 82; 82/51; 82/58; Akkermansia - classification; Akkermansia - drug effects; Akkermansia - genetics; Akkermansia - isolation & purification; Akkermansia muciniphila; Animals; Antibiotics; Blood Glucose - drug effects; Cecum; Colon; Constipation; Dextran; Diet, High-Fat - adverse effects; Digestive system; Digestive tract; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Dysbacteriosis; Endotoxemia; Endotoxins - blood; Feces - microbiology; Gastrointestinal Microbiome - drug effects; Glucose; Glucose metabolism; Glucose tolerance; Herbal medicine; High fat diet; Humanities and Social Sciences; Insulin; Intestinal microflora; Intestine; Intolerance; Lipopolysaccharide-binding protein; Lipopolysaccharides; Male; Metabolism; Mice; Microbiota; multidisciplinary; Obesity; Obesity - blood; Obesity - chemically induced; Obesity - drug therapy; Permeability; RNA, Ribosomal, 16S - genetics; rRNA 16S; Science; Science (multidisciplinary); Sequence analysis; Sequence Analysis, DNA
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-62506-w

Obesity and insulin resistance are associated with dysbiosis of the gut microbiota and impaired intestinal barrier function. Herein, we report that Bofutsushosan (BFT), a Japanese herbal medicine, Kampo, which has been clinically used for constipation in Asian countries, ameliorates glucose metabolism in mice with diet–induced obesity. A 16S rRNA sequence analysis of fecal samples showed that BFT dramatically increased the relative abundance of Verrucomicrobia, which was mainly associated with a bloom of Akkermansia muciniphila (AKK). BFT decreased the gut permeability as assessed by FITC-dextran gavage assay, associated with increased expression of tight-junction related protein, claudin-1, in the colon. The BFT treatment group also showed significant decreases of the plasma endotoxin level and expression of the hepatic lipopolysaccharide-binding protein. Antibiotic treatment abrogated the metabolic effects of BFT. Moreover, many of these changes could be reproduced when the cecal contents of BFT-treated donors were transferred to antibiotic-pretreated high fat diet-fed mice. These data demonstrate that BFT modifies the gut microbiota with an increase in AKK, which may contribute to improving gut barrier function and preventing metabolic endotoxemia, leading to attenuation of diet-induced inflammation and glucose intolerance. Understanding the interaction between a medicine and the gut microbiota may provide insights into new pharmacological targets to improve glucose metabolism.