Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway
ABSTRACT Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget d...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Microbial Biotechnology |
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| Online Access: | https://doi.org/10.1111/1751-7915.70083 |
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| author | Ruonan Zhang Xuewei Sun Han Lu Xinrui Zhang Mingyan Zhang Xuewen Ji Xinyi Yu Chengliang Tang Zihan Wu Yinghua Mao Jin Zhu Minjun Ji Zhan Yang |
| author_facet | Ruonan Zhang Xuewei Sun Han Lu Xinrui Zhang Mingyan Zhang Xuewen Ji Xinyi Yu Chengliang Tang Zihan Wu Yinghua Mao Jin Zhu Minjun Ji Zhan Yang |
| author_sort | Ruonan Zhang |
| collection | DOAJ |
| description | ABSTRACT Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear. We utilised bacterial 16S rRNA gene profiling, antimicrobial treatments, and faecal microbiota transplantation tests to explore whether DSF therapy for ALI is dependent on gut microbiota. Our findings indicate that DSF primarily restores intestinal microbiome balance by modulating the abundance of Akkermansia muciniphila (A. muciniphila), leading to significant alleviation of ALI symptoms in a gut microbiota dependent manner. We also found that A. muciniphila can promote the activation of PI3K/Akt pathway, correct the Bcl‐2/Bax ratio, and further inhibit hepatocyte apoptosis. In conclusion, DSF ameliorates ALI by modulating the intestinal microbiome and activating the PI3K/AKT pathway through A. muciniphila. |
| format | Article |
| id | doaj-art-543cf545593e415d9ec1231550d0c36e |
| institution | Kabale University |
| issn | 1751-7915 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Microbial Biotechnology |
| spelling | doaj-art-543cf545593e415d9ec1231550d0c36e2025-01-31T06:26:35ZengWileyMicrobial Biotechnology1751-79152025-01-01181n/an/a10.1111/1751-7915.70083Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt PathwayRuonan Zhang0Xuewei Sun1Han Lu2Xinrui Zhang3Mingyan Zhang4Xuewen Ji5Xinyi Yu6Chengliang Tang7Zihan Wu8Yinghua Mao9Jin Zhu10Minjun Ji11Zhan Yang12Department of Pathogen Biology Nanjing Medical University Nanjing ChinaHuadong Medical Institute of Biotechniques Nanjing ChinaThe Second Affiliated Hospital of Nanjing Medical University Nanjing ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine Nanjing ChinaJinling Clinical Medical College, Nanjing University of Chinese Medicine Nanjing ChinaSchool of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine Nanjing ChinaDepartment of Infectious Disease The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaHuadong Medical Institute of Biotechniques Nanjing ChinaHuadong Medical Institute of Biotechniques Nanjing ChinaHuadong Medical Institute of Biotechniques Nanjing ChinaHuadong Medical Institute of Biotechniques Nanjing ChinaDepartment of Pathogen Biology Nanjing Medical University Nanjing ChinaHuadong Medical Institute of Biotechniques Nanjing ChinaABSTRACT Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear. We utilised bacterial 16S rRNA gene profiling, antimicrobial treatments, and faecal microbiota transplantation tests to explore whether DSF therapy for ALI is dependent on gut microbiota. Our findings indicate that DSF primarily restores intestinal microbiome balance by modulating the abundance of Akkermansia muciniphila (A. muciniphila), leading to significant alleviation of ALI symptoms in a gut microbiota dependent manner. We also found that A. muciniphila can promote the activation of PI3K/Akt pathway, correct the Bcl‐2/Bax ratio, and further inhibit hepatocyte apoptosis. In conclusion, DSF ameliorates ALI by modulating the intestinal microbiome and activating the PI3K/AKT pathway through A. muciniphila.https://doi.org/10.1111/1751-7915.70083acetaminophenacute liver injuryAkkermansia muciniphiladisulfiramgut microbiomePI3K/Akt pathway |
| spellingShingle | Ruonan Zhang Xuewei Sun Han Lu Xinrui Zhang Mingyan Zhang Xuewen Ji Xinyi Yu Chengliang Tang Zihan Wu Yinghua Mao Jin Zhu Minjun Ji Zhan Yang Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway Microbial Biotechnology acetaminophen acute liver injury Akkermansia muciniphila disulfiram gut microbiome PI3K/Akt pathway |
| title | Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway |
| title_full | Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway |
| title_fullStr | Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway |
| title_full_unstemmed | Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway |
| title_short | Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway |
| title_sort | akkermansia muciniphila mediated the preventive effect of disulfiram on acute liver injury via pi3k akt pathway |
| topic | acetaminophen acute liver injury Akkermansia muciniphila disulfiram gut microbiome PI3K/Akt pathway |
| url | https://doi.org/10.1111/1751-7915.70083 |
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