Long-Term Tracking of the Effects of Colostrum-Derived Lacticaseibacillus rhamnosus Probio-M9 on Gut Microbiota in Mice with Colitis-Associated Tumorigenesis

Author:

Zhao Feiyan1,Hiraishi Keizo23,Li Xiaodong2ORCID,Hu Yaopeng3ORCID,Kojima Daibo4,Sun Zhihong1,Zhang Heping1,Kurahara Lin-Hai2

Affiliation:

1. Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, China

2. Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan

3. Department of Physiology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Fukuoka, Japan

4. Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Fukuoka, Japan

Abstract

Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the probiotic Probio-M9 on CAC-model mice, tracking the microbiota. Feces were obtained at four time points for evaluation of gut microbiota. The effect of Probio-M9 on tight junction protein expression was evaluated in co-cultured Caco-2 cells. Probio-M9 treatment decreased the number of tumors as well as stool consistency score, spleen weight, inflammatory score, and macrophage expression in the CAC model. Probio-M9 accelerated the recovery of the structure, composition, and function of the intestinal microbiota destroyed by azoxymethane (AOM)/dextran sulfate sodium (DSS) by regulating key bacteria (including Lactobacillus murinus, Muribaculaceae bacterium DSM 103720, Muribaculum intestinale, and Lachnospiraceae bacterium A4) and pathways from immediately after administration until the end of the experiment. Probio-M9 co-culture protected against lipopolysaccharide-induced impairment of tight junctions in Caco-2 cells. This study provides valuable insight into the role of Probio-M9 in correcting gut microbiota defects associated with inflammatory bowel disease carcinogenesis and may have clinical application in the treatment of inflammatory carcinogenesis.

Funder

KAKENHI

Inner Mongolia Science and Technology Major Projects

Asia-centered International Joint Research Promotion Fund of Kagawa University Research Promotion Program 2021

Gender Equality Promotion Office of Kagawa University

Central Research Institute of Fukuoka University

Takeda Science Foundation

Publisher

MDPI AG

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4. Gut microbiota composition and functional changes in inflammatory bowel disease and irritable bowel syndrome;Vila;Sci. Transl. Med.,2018

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