Clostridium butyricum Modulates the Microbiome to Protect Intestinal Barrier Function in Mice with Antibiotic-Induced Dysbiosis

Mao Hagihara; Yasutoshi Kuroki; Tadashi Ariyoshi; Seiya Higashi; Kazuo Fukuda; Rieko Yamashita; Asami Matsumoto; Takeshi Mori; Kaoru Mimura; Naoko Yamaguchi; Shoshiro Okada; Tsunemasa Nonogaki; Tadashi Ogawa; Kenta Iwasaki; Susumu Tomono; Nobuhiro Asai; Yusuke Koizumi; Kentaro Oka; Yuka Yamagishi; Motomichi Takahashi; Hiroshige Mikamo

doi:10.1016/j.isci.2019.100772

Clostridium butyricum Modulates the Microbiome to Protect Intestinal Barrier Function in Mice with Antibiotic-Induced Dysbiosis

iScience. 2020 Jan 24;23(1):100772. doi: 10.1016/j.isci.2019.100772. Epub 2019 Dec 13.

Authors

Mao Hagihara¹, Yasutoshi Kuroki², Tadashi Ariyoshi², Seiya Higashi³, Kazuo Fukuda³, Rieko Yamashita¹, Asami Matsumoto³, Takeshi Mori⁴, Kaoru Mimura⁵, Naoko Yamaguchi⁵, Shoshiro Okada⁵, Tsunemasa Nonogaki⁶, Tadashi Ogawa⁷, Kenta Iwasaki⁸, Susumu Tomono⁹, Nobuhiro Asai⁴, Yusuke Koizumi⁴, Kentaro Oka², Yuka Yamagishi⁴, Motomichi Takahashi², Hiroshige Mikamo¹⁰

Affiliations

¹ Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute 480-1195, Japan.
² Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Japan; Miyarisan Pharmaceutical Co., Ltd., Saitama 114-0016, Japan.
³ Miyarisan Pharmaceutical Co., Ltd., Saitama 114-0016, Japan.
⁴ Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Japan.
⁵ Department of Pharmacology, Aichi Medical University, Nagakute 480-1195, Japan.
⁶ Department of Pharmacy, College of Pharmacy Kinjo Gakuin University, Nagoya 463-8521, Japan.
⁷ Department of Legal Medicine, Aichi Medical University, Nagakute 480-1195, Japan.
⁸ Departments of Kidney Disease and Transplant Immunology, Aichi Medical University, Nagakute 480-1195, Japan.
⁹ Department of Microbiology and Immunology, Aichi Medical University, Nagakute 480-1195, Japan.
¹⁰ Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Japan. Electronic address: mikamo@aichi-med-u.ac.jp.

Abstract

Clostridium butyricum MIYAIRI 588 (CBM 588) is a probiotic bacterium that has previously been used to prevent antibiotic-associated diarrhea. However, the underlying mechanism by which CBM 588 protects the gut epithelial barrier remains unclear. Here, we show that CBM 588 increased the abundance of Bifidobacterium, Lactobacillus, and Lactococcus species in the gut microbiome and also enhanced the intestinal barrier function of mice with antibiotic-induced dysbiosis. Additionally, CBM 588 significantly promoted the expansion of IL-17A-producing γδT cells and IL-17A-producing CD4 cells in the colonic lamina propria (cLP), which was closely associated with changes in the intestinal microbial composition. Additionally, CBM 588 plays an important role in controlling antibiotic-induced gut inflammation through upregulation of anti-inflammatory lipid metabolites such as palmitoleic acid, 15d-prostaglandin J₂, and protectin D₁. This study reveals a previously unrecognized mechanism of CBM 588 and provides new insights into gut epithelial barrier protection with probiotics under conditions of antibiotic-induced dysbiosis.

Keywords: Clinical Microbiology; Microbiome.