Baoyang Xu1, Yiqin Yan1, Juncheng Huang1, Boqi Yin1, Yunxin Pan1, Libao Ma2. 1. Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. 2. Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China. Electronic address: malibao@mail.hzau.edu.cn.
Abstract
Cortex Phellodendri extract (CPE) has been used in China to treat diarrhea whereas the underlying mechanisms remain poorly understood. Given that dysbiosis of gut microbiota is a potential reason for diarrhea, and that oral CPE has a low absorption rate in intestine, we hypothesized that modification of gut microbiota is an important factor in CPE's anti-diarrhea effect. To test this hypothesis, we established a diarrhea model by challenging post-weaning mice with oral Enterotoxigenic-Escherichia coli (ETEC), and then the mice were treated with two doses of CPE (80 mg/kg bodyweight and 160 mg/kg bodyweight) or the vehicle control (phosphate buffered saline). Diarrhea indices, inflammatory factors, morphology of jejunum, short-chain fatty acids (SCFAs), and serum endocrine were determined. Modification of gut microbiota was analyzed using 16S rDNA high-throughput sequencing. The changes in functional profiles of gut microbiota were predicted using software PICRUSt. We then explored the association between CPE-responding bacteria and the symptoms indices with the spearman's rank correlation coefficient and significance test. Compared with diarrheal mice, CPE decreased Gut/Carcass ratio and water content of stool, increased goblet cell density and villus height/crypt depth of jejunum, as well as decreased inflammatory indices (Tumour Necrosis Factor-α, Myeloperoxidase and Interleukin-1α). CPE shifted the gut microbiota significantly by increasing alpha diversity (observed species, ace, Shannon, and Simpson) and restoring the gut microbiota. CPE increased Firmicutes and decreased Bacteroidetes. The reduced genus Prevotella, Acinetobacter, and Morganella were positively associated with the diarrhea indices, whereas increased genus Odoribacter, Rikenella, and Roseburia were negatively associated with the diarrhea indices. The abundance of carbohydrate metabolism-related gene and SCFAs-producing bacteria were increased, which was evidenced by increased butyric acid and total SCFAs concentration in the caecum. Consequently, endocrine peptides glucagon-like peptide-1, epidermal growth factor, and peptide tyrosine tyrosine in serum were elevated. CONCLUSIONS: CPE shows a shift function on the gut microbiota in alleviating the diarrhea of mice in a dose-dependent manner. In addition, the microbial metabolites SCFAs may mediate CPE's anti-diarrhea effect by enhancing endocrine secretion in mice.
Cortex Phellodendri extract (CPE) has been used in China to treat diarrhea whereas the underlying mechanisms remain poorly understood. Given that dysbiosis of gut microbiota is a potential reason for diarrhea, and that oral CPE has a low absorption rate in intestine, we hypothesized that modification of gut microbiota is an important factor in CPE's anti-diarrhea effect. To test this hypothesis, we established a diarrhea model by challenging post-weaning mice with oral Enterotoxigenic-Escherichia coli (ETEC), and then the mice were treated with two doses of CPE (80 mg/kg bodyweight and 160 mg/kg bodyweight) or the vehicle control (phosphate buffered saline). Diarrhea indices, inflammatory factors, morphology of jejunum, short-chain fatty acids (SCFAs), and serum endocrine were determined. Modification of gut microbiota was analyzed using 16S rDNA high-throughput sequencing. The changes in functional profiles of gut microbiota were predicted using software PICRUSt. We then explored the association between CPE-responding bacteria and the symptoms indices with the spearman's rank correlation coefficient and significance test. Compared with diarrheal mice, CPE decreased Gut/Carcass ratio and water content of stool, increased goblet cell density and villus height/crypt depth of jejunum, as well as decreased inflammatory indices (Tumour Necrosis Factor-α, Myeloperoxidase and Interleukin-1α). CPE shifted the gut microbiota significantly by increasing alpha diversity (observed species, ace, Shannon, and Simpson) and restoring the gut microbiota. CPE increased Firmicutes and decreased Bacteroidetes. The reduced genus Prevotella, Acinetobacter, and Morganella were positively associated with the diarrhea indices, whereas increased genus Odoribacter, Rikenella, and Roseburia were negatively associated with the diarrhea indices. The abundance of carbohydrate metabolism-related gene and SCFAs-producing bacteria were increased, which was evidenced by increased butyric acid and total SCFAs concentration in the caecum. Consequently, endocrine peptides glucagon-like peptide-1, epidermal growth factor, and peptide tyrosine tyrosine in serum were elevated. CONCLUSIONS:CPE shows a shift function on the gut microbiota in alleviating the diarrhea of mice in a dose-dependent manner. In addition, the microbial metabolites SCFAs may mediate CPE's anti-diarrhea effect by enhancing endocrine secretion in mice.
Authors: Zunxiang Yan; Kang Zhang; Kai Zhang; Guibo Wang; Lei Wang; Jingyan Zhang; Zhengying Qiu; Zhiting Guo; Xiaoping Song; Jianxi Li Journal: Front Vet Sci Date: 2022-02-15
Authors: Raphaële Gresse; Frédérique Chaucheyras-Durand; Juan J Garrido; Sylvain Denis; Angeles Jiménez-Marín; Martin Beaumont; Tom Van de Wiele; Evelyne Forano; Stéphanie Blanquet-Diot Journal: Front Microbiol Date: 2021-07-19 Impact factor: 5.640