A novel therapy targeting the gut–liver axis for chronic hepatitis B: Ursodeoxycholic acid plus Bifidobacterium
Background & Aims: Targeting the gut–liver axis is a promising strategy for treating liver diseases. We aimed to assess the therapeutic efficacy of targeting the gut microbiota-bile acid (BA) axis using ursodeoxycholic acid (UDCA) combined with the probiotic Bifidobacterium to treat chronic...
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2025-08-01
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| author | Zhen Xun Xiaobao Yao Caorui Lin Xinyao Yang Yanfang Zhang Xin Yang Yujue He Renquan Jiang Yanping Lan Yuchen Ye Detai Ye Shanjian Chen Ke Ma Wennan Wu Siyi Xu Bin Yang Can Liu Jing Chen Qi Zheng Qishui Ou |
| author_facet | Zhen Xun Xiaobao Yao Caorui Lin Xinyao Yang Yanfang Zhang Xin Yang Yujue He Renquan Jiang Yanping Lan Yuchen Ye Detai Ye Shanjian Chen Ke Ma Wennan Wu Siyi Xu Bin Yang Can Liu Jing Chen Qi Zheng Qishui Ou |
| author_sort | Zhen Xun |
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| description | Background & Aims: Targeting the gut–liver axis is a promising strategy for treating liver diseases. We aimed to assess the therapeutic efficacy of targeting the gut microbiota-bile acid (BA) axis using ursodeoxycholic acid (UDCA) combined with the probiotic Bifidobacterium to treat chronic hepatitis B (CHB). Methods: BA profiles were characterized by mass spectrometry, and gut microbiota composition was analyzed using 16S rRNA sequencing in patients with CHB and healthy controls (HCs). The effects of UDCA and Bifidobacterium were assessed both in a preclinical model and in a 2-month clinical trial involving 22 patients with CHB who received either UDCA (250 mg twice daily; n = 6), Bifidobacterium (2 g twice daily; n = 6), or a combination of UDCA and Bifidobacterium (n = 10). Results: UDCA was the most significantly decreased serum BA in patients with CHB compared to HCs (p <0.001), and had the strongest anti-HBV effect in vitro and in vivo. In the gut, the Bifidobacterium abundance was the most dramatically decreased fecal genus in patients with CHB (p = 0.018), and had the anti-HBV effect in vivo. Finally, combined treatment with UDCA and Bifidobacterium significantly reduced serum alanine aminotransferase (p = 0.008), HBV DNA (77% reduction; p <0.001), pregenomic RNA (59% reduction; p <0.001), and hepatitis B surface antigen (15% reduction; p = 0.002) levels. It also decreased NKG2A expression on natural killer (NK) cells and PD-1 expression on CD8+ T cells by approximately 50% (p <0.01), while enhancing secretion of granzyme B, perforin, and interferon-γ by CD8+ T and NK cells (p <0.05). These effects were superior to those achieved with either monotherapy. Conclusions: Combined treatment with UDCA and Bifidobacterium promotes CD8+ T/NK cell function and viral control in patients withCHB and may represent a promising adjunct therapy warranting further investigation. Impact and implications: Targeting the gut microbiota-bile acid axis has the potential to treat chronic hepatitis B. Results from preclinical models and a clinical trial show that combination treatment with ursodeoxycholic acid plus the probiotic Bifidobacterium exerts antiviral effects in patients with chronic hepatitis B by promoting CD8+ T cell and natural killer cell function. These findings may advance the understanding of HBV immunology and treatment options for chronic hepatitis B. Clinical Trial Number: ChiCTR2200062861. |
| format | Article |
| id | doaj-art-bb8c875dfffd4dc79312203331d94e6a |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-bb8c875dfffd4dc79312203331d94e6a2025-08-20T03:50:53ZengElsevierJHEP Reports2589-55592025-08-017810145610.1016/j.jhepr.2025.101456A novel therapy targeting the gut–liver axis for chronic hepatitis B: Ursodeoxycholic acid plus BifidobacteriumZhen Xun0Xiaobao Yao1Caorui Lin2Xinyao Yang3Yanfang Zhang4Xin Yang5Yujue He6Renquan Jiang7Yanping Lan8Yuchen Ye9Detai Ye10Shanjian Chen11Ke Ma12Wennan Wu13Siyi Xu14Bin Yang15Can Liu16Jing Chen17Qi Zheng18Qishui Ou19Department of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Clinical Research and Translation Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, ChinaDepartment of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Corresponding authors. Addresses: Department of Hepatology, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. (J. Chen), or (Q. Zheng), or Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. Tel.: +86-591-87981909, fax: 86-591-83340702. (Q. Ou)Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Corresponding authors. Addresses: Department of Hepatology, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. (J. Chen), or (Q. Zheng), or Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. Tel.: +86-591-87981909, fax: 86-591-83340702. (Q. Ou)Department of Laboratory Medicine, Fujian Key Laboratory of Laboratory Medicine, Gene Diagnosis Research Center, Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China; Corresponding authors. Addresses: Department of Hepatology, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. (J. Chen), or (Q. Zheng), or Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. Tel.: +86-591-87981909, fax: 86-591-83340702. (Q. Ou)Background & Aims: Targeting the gut–liver axis is a promising strategy for treating liver diseases. We aimed to assess the therapeutic efficacy of targeting the gut microbiota-bile acid (BA) axis using ursodeoxycholic acid (UDCA) combined with the probiotic Bifidobacterium to treat chronic hepatitis B (CHB). Methods: BA profiles were characterized by mass spectrometry, and gut microbiota composition was analyzed using 16S rRNA sequencing in patients with CHB and healthy controls (HCs). The effects of UDCA and Bifidobacterium were assessed both in a preclinical model and in a 2-month clinical trial involving 22 patients with CHB who received either UDCA (250 mg twice daily; n = 6), Bifidobacterium (2 g twice daily; n = 6), or a combination of UDCA and Bifidobacterium (n = 10). Results: UDCA was the most significantly decreased serum BA in patients with CHB compared to HCs (p <0.001), and had the strongest anti-HBV effect in vitro and in vivo. In the gut, the Bifidobacterium abundance was the most dramatically decreased fecal genus in patients with CHB (p = 0.018), and had the anti-HBV effect in vivo. Finally, combined treatment with UDCA and Bifidobacterium significantly reduced serum alanine aminotransferase (p = 0.008), HBV DNA (77% reduction; p <0.001), pregenomic RNA (59% reduction; p <0.001), and hepatitis B surface antigen (15% reduction; p = 0.002) levels. It also decreased NKG2A expression on natural killer (NK) cells and PD-1 expression on CD8+ T cells by approximately 50% (p <0.01), while enhancing secretion of granzyme B, perforin, and interferon-γ by CD8+ T and NK cells (p <0.05). These effects were superior to those achieved with either monotherapy. Conclusions: Combined treatment with UDCA and Bifidobacterium promotes CD8+ T/NK cell function and viral control in patients withCHB and may represent a promising adjunct therapy warranting further investigation. Impact and implications: Targeting the gut microbiota-bile acid axis has the potential to treat chronic hepatitis B. Results from preclinical models and a clinical trial show that combination treatment with ursodeoxycholic acid plus the probiotic Bifidobacterium exerts antiviral effects in patients with chronic hepatitis B by promoting CD8+ T cell and natural killer cell function. These findings may advance the understanding of HBV immunology and treatment options for chronic hepatitis B. Clinical Trial Number: ChiCTR2200062861.http://www.sciencedirect.com/science/article/pii/S258955592500134XChronic hepatitis BGut microbiotaBile acidImmune cellsTreatment |
| spellingShingle | Zhen Xun Xiaobao Yao Caorui Lin Xinyao Yang Yanfang Zhang Xin Yang Yujue He Renquan Jiang Yanping Lan Yuchen Ye Detai Ye Shanjian Chen Ke Ma Wennan Wu Siyi Xu Bin Yang Can Liu Jing Chen Qi Zheng Qishui Ou A novel therapy targeting the gut–liver axis for chronic hepatitis B: Ursodeoxycholic acid plus Bifidobacterium JHEP Reports Chronic hepatitis B Gut microbiota Bile acid Immune cells Treatment |
| title | A novel therapy targeting the gut–liver axis for chronic hepatitis B: Ursodeoxycholic acid plus Bifidobacterium |
| title_full | A novel therapy targeting the gut–liver axis for chronic hepatitis B: Ursodeoxycholic acid plus Bifidobacterium |
| title_fullStr | A novel therapy targeting the gut–liver axis for chronic hepatitis B: Ursodeoxycholic acid plus Bifidobacterium |
| title_full_unstemmed | A novel therapy targeting the gut–liver axis for chronic hepatitis B: Ursodeoxycholic acid plus Bifidobacterium |
| title_short | A novel therapy targeting the gut–liver axis for chronic hepatitis B: Ursodeoxycholic acid plus Bifidobacterium |
| title_sort | novel therapy targeting the gut liver axis for chronic hepatitis b ursodeoxycholic acid plus bifidobacterium |
| topic | Chronic hepatitis B Gut microbiota Bile acid Immune cells Treatment |
| url | http://www.sciencedirect.com/science/article/pii/S258955592500134X |
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