Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function

Objective To investigate whether the next-generation probiotics Akkermansia muciniphila can prevent non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC). Methods We constructed a NASH-HCC model called STAM. STAM mice received oral saline or A. muciniphila starting at 4 weeks o...

Full description

Bibliographic Details
Main Authors: ZHANG Wujian, LI Tao
Format: Article
Language:zho
Published: Magazine House of Cancer Research on Prevention and Treatment 2023-05-01
Series:Zhongliu Fangzhi Yanjiu
Subjects:
Online Access:http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.22.1259
_version_ 1797808885227061248
author ZHANG Wujian
LI Tao
author_facet ZHANG Wujian
LI Tao
author_sort ZHANG Wujian
collection DOAJ
description Objective To investigate whether the next-generation probiotics Akkermansia muciniphila can prevent non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC). Methods We constructed a NASH-HCC model called STAM. STAM mice received oral saline or A. muciniphila starting at 4 weeks of age. Liver tissues were evaluated by HE staining and oil red O staining for NASH activity, and intrahepatic expression levels of inflammatory cytokines and ileal tight junction proteins were measured by RT-PCR. Results At 8 weeks of age, the steatosis, ballooning degeneration and NAS scores, TNF-α, MCP-1, IL-1β, and IL-6 mRNA expression were significantly decreased in the STAM+A. muciniphila group (both P < 0.05) compared with those in the STAM+saline group (all P < 0.05). At 20 weeks of age, the number of liver surface tumors formed, tumor size and IL-6 level were decreased in the STAM + A. muciniphila group (all P < 0.05). A. muciniphila restored the thickness of the colon mucosal layer and the number of goblet cells in STAM mice as well as increased the mRNA expression of the tight junction proteins ZO-1, Claudin-3, and Occludin in ileal epithelial cells. Conclusion Akkermansia muciniphila can inhibit the progression of NASH to HCC by improving the intestinal barrier function and may serve as a candidate drug to prevent NASH-HCC.
first_indexed 2024-03-13T06:44:18Z
format Article
id doaj.art-70fa5f0bbe2a4a7ba0f7c0c18f6c1389
institution Directory Open Access Journal
issn 1000-8578
language zho
last_indexed 2024-03-13T06:44:18Z
publishDate 2023-05-01
publisher Magazine House of Cancer Research on Prevention and Treatment
record_format Article
series Zhongliu Fangzhi Yanjiu
spelling doaj.art-70fa5f0bbe2a4a7ba0f7c0c18f6c13892023-06-08T10:42:08ZzhoMagazine House of Cancer Research on Prevention and TreatmentZhongliu Fangzhi Yanjiu1000-85782023-05-0150546346910.3971/j.issn.1000-8578.2023.22.12598578.2023.22.1259Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier FunctionZHANG Wujian0LI Tao1Department of Anus-intestines, The First Affiliated Hospital of Heilongjiang Traditional Chinese Medicine, Harbin 150001, ChinaDepartment of Gastroenterology, Nanfang Hospital of Southern Medical University, Guangzhou 510000, ChinaObjective To investigate whether the next-generation probiotics Akkermansia muciniphila can prevent non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC). Methods We constructed a NASH-HCC model called STAM. STAM mice received oral saline or A. muciniphila starting at 4 weeks of age. Liver tissues were evaluated by HE staining and oil red O staining for NASH activity, and intrahepatic expression levels of inflammatory cytokines and ileal tight junction proteins were measured by RT-PCR. Results At 8 weeks of age, the steatosis, ballooning degeneration and NAS scores, TNF-α, MCP-1, IL-1β, and IL-6 mRNA expression were significantly decreased in the STAM+A. muciniphila group (both P < 0.05) compared with those in the STAM+saline group (all P < 0.05). At 20 weeks of age, the number of liver surface tumors formed, tumor size and IL-6 level were decreased in the STAM + A. muciniphila group (all P < 0.05). A. muciniphila restored the thickness of the colon mucosal layer and the number of goblet cells in STAM mice as well as increased the mRNA expression of the tight junction proteins ZO-1, Claudin-3, and Occludin in ileal epithelial cells. Conclusion Akkermansia muciniphila can inhibit the progression of NASH to HCC by improving the intestinal barrier function and may serve as a candidate drug to prevent NASH-HCC.http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.22.1259probioticsakkermansia muciniphilanon-alcoholic fatty liver diseasehepatocellular carcinoma
spellingShingle ZHANG Wujian
LI Tao
Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function
Zhongliu Fangzhi Yanjiu
probiotics
akkermansia muciniphila
non-alcoholic fatty liver disease
hepatocellular carcinoma
title Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function
title_full Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function
title_fullStr Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function
title_full_unstemmed Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function
title_short Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function
title_sort akkermansia muciniphila suppresses non alcoholic steatohepatitis associated liver cancer in mice by recovering intestinal barrier function
topic probiotics
akkermansia muciniphila
non-alcoholic fatty liver disease
hepatocellular carcinoma
url http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.22.1259
work_keys_str_mv AT zhangwujian akkermansiamuciniphilasuppressesnonalcoholicsteatohepatitisassociatedlivercancerinmicebyrecoveringintestinalbarrierfunction
AT litao akkermansiamuciniphilasuppressesnonalcoholicsteatohepatitisassociatedlivercancerinmicebyrecoveringintestinalbarrierfunction