Comparative study of liver injury protection by Akkermansia muciniphila and Faecalibacterium prausnitzii interventions in live and cell-free supernatant forms via targeting the hepcidin – ferroportin axis in mice with CCl₄-induced liver fibrosis
Abstract Background liver fibrosis is associated with dysregulated iron homeostasis regulated by the hepcidin-ferroportin axis, and dysbiotic gut microbiota. This study aimed to investigate the preventive and ameliorative effects of live and cell-free supernatant (CFS) forms of Akkermansia muciniphi...
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BMC
2025-07-01
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| Series: | Gut Pathogens |
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| Online Access: | https://doi.org/10.1186/s13099-025-00728-x |
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| author | Sara Ahmadi Badi Hananeh Tavakoli Aval Hamid Reza Moradi Amin Malek Seyed Amirhesam Seyedi Mehdi Davari Ahmad Bereimipour Soghra Khani Shohreh Khatami Seyed Davar Siadat |
| author_facet | Sara Ahmadi Badi Hananeh Tavakoli Aval Hamid Reza Moradi Amin Malek Seyed Amirhesam Seyedi Mehdi Davari Ahmad Bereimipour Soghra Khani Shohreh Khatami Seyed Davar Siadat |
| author_sort | Sara Ahmadi Badi |
| collection | DOAJ |
| description | Abstract Background liver fibrosis is associated with dysregulated iron homeostasis regulated by the hepcidin-ferroportin axis, and dysbiotic gut microbiota. This study aimed to investigate the preventive and ameliorative effects of live and cell-free supernatant (CFS) forms of Akkermansia muciniphila and Faecalibacterium prausnitzii, as important gut microbiota members, on liver fibrosis by targeting the hepcidin-ferroportin axis in both in vitro and in vivo models. Methods At the in vitro level, the effects of A. muciniphila and F. prausnitzii on the expression of collagen type I alpha 1 (COL1A1) and ferroportin (SLC40A1) transcripts in hepatic stellate cells (HSCs) were evaluated in transforming growth factor beta (TGFβ)-activated LX-2 cells, a human hepatic stellate cell line. In vivo, male C57BL/6 mice were intraperitoneally (IP) injected with 10% carbon tetrachloride (CCl₄) twice weekly for 6 weeks to establish the liver fibrosis model. Administration of live and CFS forms of A. muciniphila and F. prausnitzii was initiated 10 days before CCl₄ injection and continued until the end of the experiment. Liver injury and fibrosis were assessed using serum markers, hematoxylin and eosin (H&E), and Masson’s trichrome staining. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were used to evaluate the effects of the interventions on gene expression related to the hepcidin-ferroportin axis in liver, colon and brain samples. Additionally, qPCR was used to determine alterations in the relative abundance of key gut microbiota members in fecal samples. Results Both A. muciniphila and F. prausnitzii, as well as their CFS, significantly downregulated COL1A1 expression in TGFβ-activated LX-2 cells, accompanied by reduced alpha-smooth muscle actin (α-SMA) protein expression in liver tissue. In vivo, intervention with F. prausnitzii, particularly its CFS, led to a greater induction of hepatic hepcidin and ferroportin expression compared to A. muciniphila and its CFS. Serum liver injury markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH)) and iron levels were markedly improved following treatment with live F. prausnitzii and its CFS. Additionally, F. prausnitzii CFS significantly enhanced hepcidin gene expression in brain tissue, suggesting broader systemic benefits. Conclusion We demonstrated that F. prausnitzii and its CFS had greater beneficial potential than A. muciniphila and its CFS in the prevention and amelioration of liver fibrosis, likely through modulation of the hepcidin-ferroportin axis. These findings may support the development of next-generation probiotics and postbiotics for liver injury, which warrants further investigation. |
| format | Article |
| id | doaj-art-51bc5bf9eb374f5db44d0e637f7b24a3 |
| institution | Kabale University |
| issn | 1757-4749 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Gut Pathogens |
| spelling | doaj-art-51bc5bf9eb374f5db44d0e637f7b24a32025-08-20T03:46:00ZengBMCGut Pathogens1757-47492025-07-0117111810.1186/s13099-025-00728-xComparative study of liver injury protection by Akkermansia muciniphila and Faecalibacterium prausnitzii interventions in live and cell-free supernatant forms via targeting the hepcidin – ferroportin axis in mice with CCl₄-induced liver fibrosisSara Ahmadi Badi0Hananeh Tavakoli Aval1Hamid Reza Moradi2Amin Malek3Seyed Amirhesam Seyedi4Mehdi Davari5Ahmad Bereimipour6Soghra Khani7Shohreh Khatami8Seyed Davar Siadat9Microbiology Research Center, Pasteur Institute of IranMicrobiology Research Center, Pasteur Institute of IranDepartment of Basic Sciences, School of Veterinary Medicine, Shiraz UniversityMicrobiology Research Center, Pasteur Institute of IranMicrobiology Research Center, Pasteur Institute of IranMicrobiology Research Center, Pasteur Institute of IranDepartment of Biological Sciences and BioDiscovery Institute, University of North TexasDepartment of Biochemistry, Pasteur Institute of IranDepartment of Biochemistry, Pasteur Institute of IranMicrobiology Research Center, Pasteur Institute of IranAbstract Background liver fibrosis is associated with dysregulated iron homeostasis regulated by the hepcidin-ferroportin axis, and dysbiotic gut microbiota. This study aimed to investigate the preventive and ameliorative effects of live and cell-free supernatant (CFS) forms of Akkermansia muciniphila and Faecalibacterium prausnitzii, as important gut microbiota members, on liver fibrosis by targeting the hepcidin-ferroportin axis in both in vitro and in vivo models. Methods At the in vitro level, the effects of A. muciniphila and F. prausnitzii on the expression of collagen type I alpha 1 (COL1A1) and ferroportin (SLC40A1) transcripts in hepatic stellate cells (HSCs) were evaluated in transforming growth factor beta (TGFβ)-activated LX-2 cells, a human hepatic stellate cell line. In vivo, male C57BL/6 mice were intraperitoneally (IP) injected with 10% carbon tetrachloride (CCl₄) twice weekly for 6 weeks to establish the liver fibrosis model. Administration of live and CFS forms of A. muciniphila and F. prausnitzii was initiated 10 days before CCl₄ injection and continued until the end of the experiment. Liver injury and fibrosis were assessed using serum markers, hematoxylin and eosin (H&E), and Masson’s trichrome staining. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were used to evaluate the effects of the interventions on gene expression related to the hepcidin-ferroportin axis in liver, colon and brain samples. Additionally, qPCR was used to determine alterations in the relative abundance of key gut microbiota members in fecal samples. Results Both A. muciniphila and F. prausnitzii, as well as their CFS, significantly downregulated COL1A1 expression in TGFβ-activated LX-2 cells, accompanied by reduced alpha-smooth muscle actin (α-SMA) protein expression in liver tissue. In vivo, intervention with F. prausnitzii, particularly its CFS, led to a greater induction of hepatic hepcidin and ferroportin expression compared to A. muciniphila and its CFS. Serum liver injury markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH)) and iron levels were markedly improved following treatment with live F. prausnitzii and its CFS. Additionally, F. prausnitzii CFS significantly enhanced hepcidin gene expression in brain tissue, suggesting broader systemic benefits. Conclusion We demonstrated that F. prausnitzii and its CFS had greater beneficial potential than A. muciniphila and its CFS in the prevention and amelioration of liver fibrosis, likely through modulation of the hepcidin-ferroportin axis. These findings may support the development of next-generation probiotics and postbiotics for liver injury, which warrants further investigation.https://doi.org/10.1186/s13099-025-00728-xHepcidinFerroportinLiver fibrosisAkkermansia muciniphilaFaecalibacterium prausnitziiGut microbiota |
| spellingShingle | Sara Ahmadi Badi Hananeh Tavakoli Aval Hamid Reza Moradi Amin Malek Seyed Amirhesam Seyedi Mehdi Davari Ahmad Bereimipour Soghra Khani Shohreh Khatami Seyed Davar Siadat Comparative study of liver injury protection by Akkermansia muciniphila and Faecalibacterium prausnitzii interventions in live and cell-free supernatant forms via targeting the hepcidin – ferroportin axis in mice with CCl₄-induced liver fibrosis Gut Pathogens Hepcidin Ferroportin Liver fibrosis Akkermansia muciniphila Faecalibacterium prausnitzii Gut microbiota |
| title | Comparative study of liver injury protection by Akkermansia muciniphila and Faecalibacterium prausnitzii interventions in live and cell-free supernatant forms via targeting the hepcidin – ferroportin axis in mice with CCl₄-induced liver fibrosis |
| title_full | Comparative study of liver injury protection by Akkermansia muciniphila and Faecalibacterium prausnitzii interventions in live and cell-free supernatant forms via targeting the hepcidin – ferroportin axis in mice with CCl₄-induced liver fibrosis |
| title_fullStr | Comparative study of liver injury protection by Akkermansia muciniphila and Faecalibacterium prausnitzii interventions in live and cell-free supernatant forms via targeting the hepcidin – ferroportin axis in mice with CCl₄-induced liver fibrosis |
| title_full_unstemmed | Comparative study of liver injury protection by Akkermansia muciniphila and Faecalibacterium prausnitzii interventions in live and cell-free supernatant forms via targeting the hepcidin – ferroportin axis in mice with CCl₄-induced liver fibrosis |
| title_short | Comparative study of liver injury protection by Akkermansia muciniphila and Faecalibacterium prausnitzii interventions in live and cell-free supernatant forms via targeting the hepcidin – ferroportin axis in mice with CCl₄-induced liver fibrosis |
| title_sort | comparative study of liver injury protection by akkermansia muciniphila and faecalibacterium prausnitzii interventions in live and cell free supernatant forms via targeting the hepcidin ferroportin axis in mice with ccl₄ induced liver fibrosis |
| topic | Hepcidin Ferroportin Liver fibrosis Akkermansia muciniphila Faecalibacterium prausnitzii Gut microbiota |
| url | https://doi.org/10.1186/s13099-025-00728-x |
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