Michihiro Iwaki1, Takaomi Kessoku1, Anna Ozaki1, Yuki Kasai1, Takashi Kobayashi1, Asako Nogami1, Yasushi Honda1, Yuji Ogawa1, Kento Imajo1, Masato Yoneda1, Ayako Maeda2, Yoshiki Tanaka2, Shunji Nakajima2, Hiroshi Ohno2, Haruki Usuda3, Miwa Kawanaka4, Takumi Kawaguchi5, Takuji Torimura5, Masayoshi Kage6, Hideyuki Hyogo7, Hirokazu Takahashi8,9, Yuichiro Eguchi9, Shinichi Aishima10, Koichiro Wada3, Noritoshi Kobayashi11, Yoshio Sumida12, Satoru Saito1, Atsushi Nakajima1. 1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. 2. Biofermin Pharmaceutical Co., Ltd, Kobe, Japan. 3. Department of Pharmacology, Faculty of Medicine, Shimane University, Izumo, Japan. 4. Department of General Internal Medicine 2, Kawasaki Medical Center, Kawasaki Medical School, Kurashiki, Japan. 5. Division of Gastroenterology, Department of Medicine, School of Medicine, Kurume University, Kurume, Japan. 6. Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan. 7. Department of Gastroenterology, JA Hiroshima Kouseiren General Hospital, Hatsukaichi, Japan. 8. Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan. 9. Liver Center, Saga University Hospital, Saga, Japan. 10. Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan. 11. Department of Oncology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. 12. Division of Hepatology and Pancreatology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Nagakute, Japan.
Abstract
BACKGROUND AND AIM: Gut microbiota composition is associated with the pathogenesis of non-alcoholic fatty liver disease. However, the association between gut microbiota composition and non-alcoholic fatty liver disease in non-obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non-obese and obese patients with non-alcoholic fatty liver disease. METHODS: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short-chain fatty acid levels in fecal samples from 51 non-obese patients with non-alcoholic fatty liver disease (body mass index <25 kg/m2 ) and 51 obese patients with non-alcoholic fatty liver disease (body mass index ≥30 kg/m2 ) who underwent pathological examination and 87 controls at five hospitals in Japan. RESULTS: Although no significant differences between the non-obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non-obese patients with non-alcoholic fatty liver disease compared with those in obese patients with non-alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non-obese patients with non-alcoholic fatty liver disease. CONCLUSIONS: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non-alcoholic fatty liver disease in non-obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917).
BACKGROUND AND AIM: Gut microbiota composition is associated with the pathogenesis of non-alcoholic fatty liver disease. However, the association between gut microbiota composition and non-alcoholic fatty liver disease in non-obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non-obese and obese patients with non-alcoholic fatty liver disease. METHODS: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short-chain fatty acid levels in fecal samples from 51 non-obese patients with non-alcoholic fatty liver disease (body mass index <25 kg/m2 ) and 51 obese patients with non-alcoholic fatty liver disease (body mass index ≥30 kg/m2 ) who underwent pathological examination and 87 controls at five hospitals in Japan. RESULTS: Although no significant differences between the non-obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non-obese patients with non-alcoholic fatty liver disease compared with those in obese patients with non-alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non-obese patients with non-alcoholic fatty liver disease. CONCLUSIONS: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non-alcoholic fatty liver disease in non-obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917).