A Synbiotic Ameliorates Con A-Induced Autoimmune Hepatitis in Mice through Modulation of Gut Microbiota and Immune Imbalance
Qingqing Liu
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
LinFen Central Hospital, LinFen, 041000 China
Search for more papers by this authorHao Yang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorXing Kang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorHaixia Tian
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorYongbo Kang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorLin Li
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorXiaodan Yang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorHaixia Liu
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorPeng Ren
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorXiaoyu Kuang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorMingwei Tong
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorCorresponding Author
Weiping Fan
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Jinzhong, 030619 China
E-mail: [email protected]
Search for more papers by this authorQingqing Liu
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
LinFen Central Hospital, LinFen, 041000 China
Search for more papers by this authorHao Yang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorXing Kang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorHaixia Tian
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorYongbo Kang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorLin Li
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorXiaodan Yang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorHaixia Liu
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorPeng Ren
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorXiaoyu Kuang
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorMingwei Tong
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Jinzhong, 030619 China
Search for more papers by this authorCorresponding Author
Weiping Fan
Department of Microbiology and Immunology, Shanxi Medical University, Jinzhong, 030619 China
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Jinzhong, 030619 China
E-mail: [email protected]
Search for more papers by this authorAbstract
Scope
Changes in the intestinal flora are related to autoimmune hepatitis (AIH) development. The aim of this study is to investigate the synergistic effects of probiotics and prebiotics on liver injury induced by concanavalin A (Con A).
Methods and results
C57BL/6 mice are fed probiotics (Pro), prebiotics (Pre), synbiotic (Syn) for 7 days and then Con A is injected via tail veins to induce AIH. Additionally, methylprednisolone (MP) is gavaged 0.5 h after the Con A injection. It is found that both Pro, Pre, Syn, and MP decrease the levels of serum transaminase, liver F4/80+ macrophage cells, and hepatocellular apoptosis. Pro, Pre, and Syn decrease proinflammatory cytokines, elevate levels of anti-inflammatory as well as restored immune imbalance in AIH. Besides, Pro, Pre, and Syn not only reshape the perturbed gut microbiota, but also maintain intestinal barrier integrity, block the activation of lipopolysaccharide (LPS)/TLR4/NF-κB pathway in the liver. Interestingly, the effects of Syn are superior to Pro or Pre alone in Con A-induced acute liver injury.
Conclusions
Syn obviously facilitates AIH remission. The combined use of Pro and Pre is effective in improving Pro and Pre efficacy and can be an important tool for preventing and adjuvant treating patients for AIH.
Conflict of Interest
The authors declare no conflict of interests.
Open Research
Data Availability Statement
The data that support the findings of this study are openly available in the BioSample database at http://www.ncbi.nlm.nih.gov/bioproject/925295, reference number [PRJNA925295].
Supporting Information
| Filename | Description |
|---|---|
| mnfr4394-sup-0001-SuppMat.pdf433.9 KB | Abbreviations The abbreviations summarizing the main notation that has been adopted were shown in Supporting Information Table S2. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1G. N. Dalekos, J. Koskinas, G. V. Papatheodoridis, Ann. Gastroenterol. 2019, 32, 1.
- 2G. J. Webb, G. M. Hirschfield, E. L. Krawitt, M. E. Gershwin, Annu. Rev. Pathol. 2018, 13, 247.
- 3N. Cazzagon, S. Sarcognato, A. Floreani, G. Corrà, S. De Martin, V. Guzzardo, F. P. Russo, M. Guido, JHEP Rep. 2021, 3, 100286.
- 4Y. Yang, M. Yan, H. Zhang, X. Wang, Exp. Ther. Med. 2013, 6, 459.
- 5Y. Wei, B. Zeng, J. Chen, G. Cui, C. Lu, W. Wu, J. Yang, H. Wei, R. Xue, L. Bai, Z. Chen, L. Li, K. Iwabuchi, T. Uede, L. Van Kaer, H. Diao, Sci. Rep. 2016, 6, 36365.
- 6T. Liwinski, C. Casar, M. C. Ruehlemann, C. Bang, M. Sebode, S. Hohenester, G. Denk, W. Lieb, A. W. Lohse, A. Franke, C. Schramm, Aliment. Pharmacol. Ther. 2020, 51, 1417.
- 7Y. Wei, Y. Li, L. Yan, C. Sun, Q. Miao, Q. Wang, X. Xiao, M. Lian, B. Li, Y. Chen, J. Zhang, Y. Li, B. Huang, Y. Li, Q. Cao, Z. Fan, X. Chen, J. Y. Fang, M. E. Gershwin, R. Tang, X. Ma, Gut. 2020, 69, 569.
- 8K. R. Pandey, S. R. Naik, B. V. Vakil, J. Food Sci. Technol. 2015, 52, 7577.
- 9M.-M. Zhang, World J. Gastroenterol. 2010, 16, 3970.
- 10H. Jiang, R. Yan, K. Wang, Q. Wang, X. Chen, L. Chen, L. Li, Lv. L. 2021, 133, 111000.
- 11L. Lv, C. Yao, R. Yan, H. Jiang, Q. Wang, K. Wang, S. Ren, S. Jiang, J. Xia, S. Li, Y. Yu, mSystems 2021, 6, e0038421.
- 12K. Wang, L. Lv, R. Yan, Q. Wang, H. Jiang, W. Wu, Y. Li, J. Ye, J. Wu, L. Yang, X. Bian, X. Jiang, Y. Lu, J. Xie, Q. Wang, J. Shen, L. Li, mSphere 2020, 5, e00791.
- 13N. Kobyliak, L. Abenavoli, G. Mykhalchyshyn, L. Kononenko, L. Boccuto, D. Kyriienko, O. Dynnyk, J. Gastrointestin. Liver Dis. 2018, 27, 41.
- 14G. Leccese, A. Bibi, S. Mazza, F. Facciotti, F. Caprioli, P. Landini, M. Paroni, Cells 2020, 9, 1824.
- 15A. Consonni, C. Cordiglieri, E. Rinaldi, R. Marolda, I. Ravanelli, E. Guidesi, M. Elli, R. Mantegazza, F. Baggi, OncoTargets Ther. 2018, 9, 22269.
10.18632/oncotarget.25170 Google Scholar
- 16Q. Liu, H. Tian, Y. Kang, Y. Tian, L. Li, X. Kang, H. Yang, Y. Wang, J. Tian, F. Zhang, M. Tong, H. Cai, W. Fan, J. Nutr. Biochem. 2021, 98, 108863.
- 17M. K. Yadav, I. Kumari, B. Singh, K. K. Sharma, S. K. Tiwari, Appl. Microbiol. Biotechnol. 2022, 106, 505.
- 18B. Pourrajab, S. Fatahi, M. H. Sohouli, M.-A. Gaman, F. Shidfar, Crit. Rev. Food Sci. Nutr. 2022, 62, 490.
- 19Q. Liu, Z. P. Duan, D. K. Ha, S. Bengmark, J. Kurtovic, S. M. Riordan, Hepatology 2004, 39, 1441.
- 20T. Tang, J. Song, J. Li, H. Wang, Y. Zhang, H. Suo, Carbohydr. Polym. 2020, 243, 116398.
- 21G. Liu, W. Zhao, J. Bai, J. Cui, H. Liang, B. Lu, Biochem. Cell Biol. 2021, 99, 231.
- 22H. Wang, Y. Zhao, B. Ren, Y. Qin, G. Li, D. Kong, H. Qin, J. Hao, D. Sun, H. Wang, Stem. Cell Res. Ther. 2021, 12, 541.
- 23M.-C. Hsu, S.-H. Liu, C.-W. Wang, N.-Y. Hu, E. S. C. Wu, Y.-C. Shih, P. J. S. Chiu, Eur. J. Pharmacol. 2017, 812, 113.
- 24J. Fang, J. She, F. Lin, J.-C. Wu, R. Han, R. Sheng, G. Wang, Z.-H. Qin, Front. Pharmacol. 2022, 13, 889383.
- 25J. Chen, Y. Wei, J. He, G. Cui, Y. Zhu, C. Lu, Y. Ding, R. Xue, L. Bai, T. Uede, L. Li, H. Diao, Sci. Rep. 2014, 4, 7259.
- 26L. Yang, Q. Ao, Q. Zhong, W. Li, W. Li, Basic Clin. Pharmacol. Toxicol. 2020, 127, 371.
- 27M. Leist, A. Wendel, J. Hepatol. 1996, 25, 948.
- 28B. Terziroli Beretta-Piccoli, G. Mieli-Vergani, D. Vergani, Cell Mol. Immunol. 2022, 19, 158.
- 29W. Wu, L. Lv, D. Shi, J. Ye, D. Fang, F. Guo, Y. Li, X. He, L. Li, Front. Microbiol. 2017, 8, 1804.
- 30L.-M. Liu, W.-J. Tu, T. Zhu, X.-T. Wang, Z.-L. Tan, H. Zhong, D.-Y. Gao, D.-Y. Liang, OncoTargets Ther. 2016, 7, 49027.
- 31W. Wu, L. Lv, D. Shi, J. Ye, D. Fang, F. Guo, Y. Li, X. He, L. Li, Front. Microbiol. 2017, 8, 1804.
- 32L. Yang, X. Bian, W. Wu, L. Lv, Y. Li, J. Ye, X. Jiang, Q. Wang, D. Shi, D. Fang, J. Wu, K. Wang, Q. Wang, J. Xia, J. Xie, Y. Lu, L. Li, Microb. Biotechnol. 2020, 13, 1860.
- 33L. Fontana, J. Plaza-Díaz, P. Robles-Bolívar, H. Valente-Godínez, M. J. Sáez-Lara, F. Abadía-Molina, C. Gómez-Llorente, Á. Gil, A. I. Álvarez-Mercado, Nutrients. 2021, 13, 202.
- 34T.-J. Lim, S. Lim, J. H. Yoon, M. J. Chung, J. Microbiol. 2021, 59, 417.
- 35H. Wu, S. Tang, M. Zhou, J. Xue, Z. Yu, J. Zhu, FEBS Open Bio. 2021, 11, 1406.
- 36J. Sun, P. Kumar Panda, S. Kumar Samal, R. Ahuja, S. Ajeganova, I. Hafström, A. Liu, J. Frostegård, ACR Open Rheumatol. 2021, 3, 642.
- 37J. Han, W. Zhuang, W. Feng, F. Dong, F. Hua, R. Yao, X. Qu, Cell Mol. Immunol. 2021, 18, 2177.
- 38O. Palomares, M. Martín-Fontecha, R. Lauener, C. Traidl-Hoffmann, O. Cavkaytar, M. Akdis, C. A. Akdis, Genes. Immun. 2014, 15, 511.
- 39H. Wang, X. Feng, W. Yan, D. Tian, Front Immunol. 2020, 11, 575572.
- 40T. Liwinski, C. Casar, M. C. Ruehlemann, C. Bang, M. Sebode, S. Hohenester, G. Denk, W. Lieb, A. W. Lohse, A. Franke, C. Schramm, Aliment. Pharmacol. Ther. 2020, 51, 1417.
- 41C. Chelakkot, Y. Choi, D.-K. Kim, H. T. Park, J. Ghim, Y. Kwon, J. Jeon, M.-S. Kim, Y.-K. Jee, Y. S. Gho, H.-S. Park, Y.-K. Kim, S. H. Ryu, Exp. Mol. Med. 2018, 50, e450.
- 42H. R. Wardill, S. A. R. Van Der Aa, A. R. Da Silva Ferreira, R. Havinga, W. J. E. Tissing, H. J. M. Harmsen, Eur. J. Cancer 2021, 153, 27.
- 43Q. Liu, B.-Y. Cai, L.-X. Zhu, X. Xin, X. Wang, Z.-M. An, S. Li, Y.-Y. Hu, Q. Feng, Life Sci. 2020, 261, 118457.
- 44R. Bubnov, L. Babenko, L. Lazarenko, M. Kryvtsova, O. Shcherbakov, N. Zholobak, O. Golubnitschaja, M. Spivak, EPMA J. 2019, 10, 317.
- 45G. R. Gibson, R. Hutkins, M. E. Sanders, S. L. Prescott, R. A. Reimer, S. J. Salminen, K. Scott, C. Stanton, K. S. Swanson, P. D. Cani, K. Verbeke, G. Reid, Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 491.
- 46M. Deng, F. Qu, L. Chen, C. Liu, M. Zhang, F. Ren, H. Guo, H. Zhang, S. Ge, C. Wu, L. Zhao, J. Endocrinol. 2020, 245, 425.
- 47K. R. Pandey, S. R. Naik, B. V. Vakil, J. Food Sci. Technol. 2015, 52, 7577.
- 48L.-H. Lian, X. Jin, Y.-L. Wu, X. F. Cai, J. J. Lee, J.-X. Nan, J. Pharmacol. Sci. 2010, 114, 147.
- 49X. Fan, Y. Zhang, H. Dong, B. Wang, H. Ji, X. Liu, Food Chem. 2015, 166, 609.
- 50J. Xu, X. Zhang, M. Monestier, N. L. Esmon, C. T. Esmon, J. Immunol. 2011, 187, 2626.
- 51M. Arumugam, J. Raes, E. Pelletier, D. Le Paslier, T. Yamada, D. R. Mende, G. R. Fernandes, J. Tap, T. Bruls, J.-M. Batto, M. Bertalan, N. Borruel, F. Casellas, L. Fernandez, L. Gautier, T. Hansen, M. Hattori, T. Hayashi, M. Kleerebezem, K. Kurokawa, M. Leclerc, F. Levenez, C. Manichanh, H. B. Nielsen, T. Nielsen, N. Pons, J. Poulain, J. Qin, T. Sicheritz-Ponten, S. D. Tims, et al., Nature 2011, 473, 174.
- 52C. Liang, X.-H. Zhou, Y.-H. Jiao, M.-J. Guo, L. Meng, P.-M. Gong, L.-Z. Lyu, H.-Y. Niu, Y.-F. Wu, S.-W. Chen, X. Han, L.-W. Zhang, Mol. Nutr. Food Res. 2021, 65, 2100136.
- 53Y.-H. Chen, C.-C. Chiu, S.-W. Hung, W.-C. Huang, Y.-P. Lee, J.-Y. Liu, Y.-T. Huang, T.-H. Chen, H.-L. Chuang, Nutr. Res. 2019, 69, 20.
- 54X. Fan, R. Men, H. Wang, M. Shen, T. Wang, T. Ye, X. Luo, L. Yang, Front. Pharmacol. 2019, 10, 1189.
- 55 Ministry of Health of the People′s Republic of China, (2010) NO.65:the species list can be used for food[EB/OL]. 2010. (in Chinese) ht tps://doi.org/.
- 56Y. Bouhnik, K. Vahedi, L. Achour, A. Attar, J. R. M. Salfati, P. Pochart, P. Marteau, B. Flourie?, F. Bornet, J.-C. Rambaud, J. Nutr. 1999, 129, 113.
- 57S. Reagan-Shaw, M. Nihal, N. Ahmad, FASEB J. 2008, 22, 659.
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