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Professor Jiro Nakayama and his research team have demonstrated that the elimination of hepatitis C virus (HCV) leads to a dramatic restoration of the intestinal microbiota.
An increase of Blautia species may be the key to liver function recovery
Points
- Our research group previously analyzed the gut microbiota*1 of patients with chronic hepatitis C and reported how the intestinal environment changes depending on the disease stage. We found that dysbiosis*2 begins in the early stages of chronic hepatitis C and worsens as the disease progresses, with an increase in oral streptococci possessing the enzyme urease*3.
(Inoue T, Nakayama J, and Tanaka Y et al., 2018. Clinical Infectious Diseases) - In the present study, we compared the gut microbiota, fecal bile acid*4 composition, and hepatic expression levels of bile acid-synthesizing enzyme genes between patients infected with hepatitis C virus (HCV) and those who had successfully eliminated the virus through treatment. The results revealed that, following viral clearance, the intestinal environment shifted toward a healthier state.
- In particular, an increase in Blautia*5-a genus of beneficial bacteria-within the gut microbiota was found to be strongly associated with improvements in liver fibrosis*6 and recovery of liver function. Furthermore, patients who received treatment at an earlier stage of the disease (chronic hepatitis) exhibited more favorable restoration of their intestinal environment.
- These findings indicate that dysbiosis caused by chronic hepatitis C is reversible following HCV elimination, and that early treatment plays a crucial role in restoring the gut-microbiota-liver axis.
Abstract
Associate Professor Takako Inoue of Nagoya City University Graduate School of Medical Sciences, Professor Yasuhito Tanaka of Kumamoto University Graduate School of Medical Sciences, and Professor Jiro Nakayama of Kyushu University Faculty of Agriculture, along with their research team, conducted a multifaceted analysis of changes in the intestinal environment and liver condition in chronic hepatitis C patients following antiviral treatment. Their approach included examining gut microbiota composition, fecal bile acid profiles, and hepatic gene expression related to bile acid synthesis.
The results showed that during HCV infection, there was an increase in oral Streptococcus*7 species within the gut microbiota and alteration in gut bile acid profiles which were associated with to an abnormal expression of bile acid-synthesizing enzyme genes in the liver. However, these alterations were restored following viral elimination. Notably, an increase in Blautia, a beneficial bacterial genus, was significantly associated with improvements in liver fibrosis and reductions in ALT levels, indicating an association between gut microbiota restoration and liver function recovery.
Moreover, patients who underwent antiviral treatment during the early stages of the disease, such as chronic hepatitis, exhibited more pronounced recovery of their intestinal environment. In contrast, those who had already progressed to liver cirrhosis showed limited improvement. These findings further underscore the importance of early intervention in chronic hepatitis C treatment.
The findings of this study were published online in the hepatology journal JHEP Reports on June 24, 2025.
Glossary
*1 Gut Microbiota:
The gut microbiota refers to the ecosystem of microorganisms residing in the intestines. More than 100 trillion bacteria inhabit the gut, utilizing dietary components and endogenous substances to produce various metabolites. These microbial activities influence both the maintenance of health and the progression of disease.
*2 Dysbiosis:
Dysbiosis refers to an imbalance in the composition of the gut microbiota, characterized by reduced bacterial diversity (simplification), abnormal increases in typically rare bacterial species, and decreases in normally abundant ones.
*3 Urease:
Urease is an enzyme that hydrolyzes urea into ammonia and carbon dioxide.
*4 Bile Acids:
Bile acids are cholesterol-derived metabolites with antimicrobial properties and roles in metabolic regulation. They are secreted by the liver into the duodenum, reabsorbed through the intestinal tract, and returned to the liver via the enterohepatic circulation. The five major bile acids commonly found in human feces are cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, and ursodeoxycholic acid.
*5 Blautia Bacteria:
Blautia is a genus of Gram-positive, coccoid bacteria considered beneficial to gut health. In Japanese populations, a higher abundance of Blautia has been associated with a reduced risk of obesity and type 2 diabetes. It is therefore gaining attention as a "health-promoting gut bacterium."
*6 Liver Fibrosis:
Liver fibrosis refers to the hardening of liver tissue resulting from repeated injury. If the condition progresses, it can progress to cirrhosis.
*7 Oral Streptococcus:
Oral Streptococcus refers to Gram-positive, coccoid bacteria characterized by their chain-like arrangement. They are common commensals in the oral cavity and can also proliferate in the intestinal tract.
Publication Information
Title: Restoration of the gut-microbiota-liver axis after hepatitis C virus eradication
Authors: Takako Inoue1#, Jiro Nakayama2#, Hiroshi Mori3, Masaru Tanaka2,4, Daisuke Nakagawa2, Masaya Ohnishi5,6, Yui Funatsu2, Kei Moriya7, Hideto Kawaratani7, Hisayashi Watanabe8, Goki Suda9, Yasuteru Kondo10,11,12, Tatsuya Ide13, Satoru Kakizaki14, Satoshi Miuma15, Atsushi Suetsugu5, Kazuhito Kawata16, Takao Watanabe17, Etsuko Iio12, Rie Momoda2, Yutaka Suzuki6, Akira Sakamaki18, Tsunamasa Watanabe19, Takehisa Watanabe12, Katsuya Nagaoka12, Yoichi Hiasa17, Shuji Terai18, Hitoshi Yoshiji7, Atsushi Toyoda3, Ken Kurokawa3, Yasuhito Tanaka12＊ (# indicates co-first authors, * indicates corresponding author)
Affiliated institutions: 1.Nagoya City University, 2.Kyushu University, 3.National Institute of Genetics, 4.JSR Corporation, 5.Gifu University,6.The University of Tokyo, 7.Nara Medical University, 8.Tohoku Central Hospital, Mutual Aid Association of Public School Teachers, 9.Hokkaido University, 10.Sendai Kosei Hospital, 11.Sendai Tokushukai Hospital, 12.Kumamoto University, 13.Kurume University, 14.Takasaki General Medical Center, 15.Nagasaki University, 16.Hamamatsu University School of Medicine, 17.Ehime University, 18.Niigata University, 20.St. Marianna University School of MedicineHEP Reports
DOI：10.1016/j.jhepr.2025.101494
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