Prasant Kumar Jena1, Lili Sheng1, Yongchun Li1,2,3, Yui-Jui Yvonne Wan1. 1. Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA. 2. Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. 3. Department of Infectious Diseases, Nanhai Hospital, Southern Medical University, Foshan 528200, China.
Abstract
BACKGROUND: Probiotic VSL#3 is used to treat ulcerative colitis. This study examines the effect of VSL#3 in non-alcoholic steatohepatitis (NASH) that has liver carcinogenic potential. METHODS: Western diet (WD)-fed wild-type (WT) mice that do not have hepatic inflammation with lymphocyte infiltration and carcinogenic potential were used for baseline comparison. Age-, sex-, and diet-matched bile acid (BA) receptor farnesoid X receptor (FXR) knockout (KO) mice, which developed severe NASH and had the potential for liver cancer development, were supplemented with and without VSL#3 for 7 months. All the mice were euthanized when they were 10 months old. RESULTS: Supplementation with VSL#3 completely abolished hepatic lymphocyte infiltration, reduced hepatic fat content, and improved insulin sensitivity in WD-fed FXR KO mice. In addition, VSL#3 normalized dysregulated BA homoeostasis by inhibiting the classical BA synthesis pathway, inducing the alternative BA pathway, and activating ileal G-protein coupled BA receptor 1 (GPBAR1)-regulated signaling. Moreover, VSL#3 reconstructed the gut microbiota by reducing Bacteroidaceae, Porphyromonadaceae, and Helicobacteraceae as well as increasing Lachnospiraceae. Further, VSL#3 enriched the abundance of Ruminococcus and Faecalibacterium, which generate butyrate, at the genus level. It also increased the copy number of the butyrate-producing genes bcoA and buk, suggesting their anti-inflammatory and metabolic effects. CONCLUSIONS: VSL#3 is useful in reversing NASH that occurred due to dysregulated BA synthesis and dysbiosis, suggesting its potential in liver cancer prevention. 2020 Hepatobiliary Surgery and Nutrition. All rights reserved.
BACKGROUND: Probiotic VSL#3 is used to treat ulcerative colitis. This study examines the effect of VSL#3 in non-alcoholic steatohepatitis (NASH) that has liver carcinogenic potential. METHODS: Western diet (WD)-fed wild-type (WT) mice that do not have hepatic inflammation with lymphocyte infiltration and carcinogenic potential were used for baseline comparison. Age-, sex-, and diet-matched bile acid (BA) receptor farnesoid X receptor (FXR) knockout (KO) mice, which developed severe NASH and had the potential for liver cancer development, were supplemented with and without VSL#3 for 7 months. All the mice were euthanized when they were 10 months old. RESULTS: Supplementation with VSL#3 completely abolished hepatic lymphocyte infiltration, reduced hepatic fat content, and improved insulin sensitivity in WD-fed FXR KO mice. In addition, VSL#3 normalized dysregulated BA homoeostasis by inhibiting the classical BA synthesis pathway, inducing the alternative BA pathway, and activating ileal G-protein coupled BA receptor 1 (GPBAR1)-regulated signaling. Moreover, VSL#3 reconstructed the gut microbiota by reducing Bacteroidaceae, Porphyromonadaceae, and Helicobacteraceae as well as increasing Lachnospiraceae. Further, VSL#3 enriched the abundance of Ruminococcus and Faecalibacterium, which generate butyrate, at the genus level. It also increased the copy number of the butyrate-producing genes bcoA and buk, suggesting their anti-inflammatory and metabolic effects. CONCLUSIONS: VSL#3 is useful in reversing NASH that occurred due to dysregulated BA synthesis and dysbiosis, suggesting its potential in liver cancer prevention. 2020 Hepatobiliary Surgery and Nutrition. All rights reserved.
Entities:
Keywords:
Bile acid (BA); G-protein coupled bile acid receptor-1 (GPBAR1); farnesoid X receptor (FXR); inflammation; microbiota
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