Viral Liver Disease and Intestinal Gut–Liver Axis
Abstract
:1. Introduction
2. The Gut–Liver Axis
2.1. Physical Elements of the Intestinal Barrier
2.2. Control of the Microbiota by the Gut-Associated Lymphoid Tissue
2.3. Stratification of the Microbiota by Mucus
3. HBV Infection and Intestinal Microbiota
3.1. HBV and Intestinal Dysbiosis
3.2. Microbiota and Immune Responses in HBV
3.3. Microbiota and HBV Treatment
4. HCV Infection and Intestinal Microbiota
Effect of HCV Treatment on Intestinal Microbiota
5. Other Hepatitis Viruses (A, D, and E)
6. Cirrhosis and Intestinal Microbiota
6.1. Involvement of Microbiota in the Pathogenesis of Cirrhosis
6.2. Microbiota and HE
6.3. HBV Cirrhosis
6.4. HBV-Related HCC
6.5. HCV Cirrhosis
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Cohn, R. A brief history of the portal circulation. AMA Arch. Intern. Med. 1957, 100, 848–852. [Google Scholar] [CrossRef]
- Ursell, L.K.; Metcalf, J.L.; Parfrey, L.W.; Knight, R. Defining the human microbiome. Nutr. Rev. 2012, 70, S38–S44. [Google Scholar] [CrossRef]
- Turnbaugh, P.J.; Ley, R.E.; Hamady, M.; Fraser-Liggett, C.M.; Knight, R.; Gordon, J.I. The human microbiome project. Nature 2007, 449, 804–810. [Google Scholar] [CrossRef]
- De Sordi, L.; Lourenço, M.; Debarbieux, L. The Battle Within: Interactions of Bacteriophages and Bacteria in the Gastrointestinal Tract. Cell Host Microbe. 2019, 25, 210–218. [Google Scholar] [CrossRef]
- Bhattarai, Y.; Muniz Pedrogo, D.A.; Kashyap, P.C. Irritable bowel syndrome: A gut microbiota-related disorder? Am. J. Physiol. Gastrointest. Liver Physiol. 2017, 312, G52–G62. [Google Scholar] [CrossRef]
- Catinean, A.; Neag, M.A.; Muntean, D.M.; Bocsan, I.C.; Buzoianu, A.D. An overview on the interplay between nutraceuticals and gut microbiota. PeerJ 2018, 6, e4465. [Google Scholar] [CrossRef]
- Philips, C.A.; Augustine, P.; Yerol, P.K.; Ramesh, G.N.; Ahamed, R.; Rajesh, S.; George, T.; Kumbar, S. Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease. J. Clin. Transl. Hepatol. 2020, 8, 87–99. [Google Scholar] [CrossRef]
- Milosevic, I.; Vujovic, A.; Barac, A.; Djelic, M.; Korac, M.; Radovanovic Spurnic, A.; Gmizic, I.; Stevanovic, O.; Djordjevic, V.; Lekic, N.; et al. Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. Int. J. Mol. Sci. 2019, 20, 395. [Google Scholar] [CrossRef]
- Reyes, A.; Semenkovich, N.P.; Whiteson, K.; Rohwer, F.; Gordon, J.I. Going viral: Next-generation sequencing applied to phage populations in the human gut. Nat. Rev. Microbiol. 2012, 10, 607–617. [Google Scholar] [CrossRef]
- Ringel, Y.; Maharshak, N.; Ringel-Kulka, T.; Wolber, E.A.; Sartor, R.B.; Carroll, I.M. High throughput sequencing reveals distinct microbial populations within the mucosal and luminal niches in healthy individuals. Gut Microbes 2015, 6, 173–181. [Google Scholar] [CrossRef]
- Mariat, D.; Firmesse, O.; Levenez, F.; Guimarăes, V.; Sokol, H.; Doré, J.; Corthier, G.; Furet, J.P. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 2009, 9, 123. [Google Scholar] [CrossRef]
- Claesson, M.J.; Cusack, S.; O’Sullivan, O.; Greene-Diniz, R.; de Weerd, H.; Flannery, E.; Marchesi, J.R.; Falush, D.; Dinan, T.; Fitzgerald, G.; et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc. Natl. Acad. Sci. USA 2011, 108, 4586–4591. [Google Scholar] [CrossRef]
- Jalanka-Tuovinen, J.; Salonen, A.; Nikkilä, J.; Immonen, O.; Kekkonen, R.; Lahti, L.; Palva, A.; de Vos, W.M. Intestinal microbiota in healthy adults: Temporal analysis reveals individual and common core and relation to intestinal symptoms. PLoS ONE 2011, 6, e23035. [Google Scholar] [CrossRef]
- Lin, A.; Bik, E.M.; Costello, E.K.; Dethlefsen, L.; Haque, R.; Relman, D.A.; Singh, U. Distinct distal gut microbiome diversity and composition in healthy children from Bangladesh and the United States. PLoS ONE 2013, 8, e53838. [Google Scholar] [CrossRef]
- Chong, C.W.; Ahmad, A.F.; Lim, Y.A.; Teh, C.S.; Yap, I.K.; Lee, S.C.; Chin, Y.T.; Loke, P.; Chua, K.H. Effect of ethnicity and socioeconomic variation to the gut microbiota composition among pre-adolescent in Malaysia. Sci. Rep. 2015, 5, 13338. [Google Scholar] [CrossRef]
- Zhang, J.; Guo, Z.; Xue, Z.; Sun, Z.; Zhang, M.; Wang, L.; Wang, G.; Wang, F.; Xu, J.; Cao, H.; et al. A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles, geography and ethnicities. ISME J. 2015, 9, 1979–1990. [Google Scholar] [CrossRef]
- Rampelli, S.; Schnorr, S.L.; Consolandi, C.; Turroni, S.; Severgnini, M.; Peano, C.; Brigidi, P.; Crittenden, A.N.; Henry, A.G.; Candela, M. Metagenome Sequencing of the Hadza Hunter-Gatherer Gut Microbiota. Curr. Biol. 2015, 25, 1682–1693. [Google Scholar] [CrossRef]
- Segata, N. Gut Microbiome: Westernization and the Disappearance of Intestinal Diversity. Curr. Biol. 2015, 25, R611–R613. [Google Scholar] [CrossRef]
- De Filippo, C.; Cavalieri, D.; Di Paola, M.; Ramazzotti, M.; Poullet, J.B.; Massart, S.; Collini, S.; Pieraccini, G.; Lionetti, P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. USA 2010, 107, 14691–14696. [Google Scholar] [CrossRef]
- Raimondi, S.; Amaretti, A.; Gozzoli, C.; Simone, M.; Righini, L.; Candeliere, F.; Brun, P.; Ardizzoni, A.; Colombari, B.; Paulone, S.; et al. Longitudinal Survey of Fungi in the Human Gut: ITS Profiling, Phenotyping, and Colonization. Front. Microbiol. 2019, 10, 1575. [Google Scholar] [CrossRef]
- Biedermann, L.; Rogler, G. The intestinal microbiota: Its role in health and disease. Eur. J. Pediatr. 2015, 174, 151–167. [Google Scholar] [CrossRef]
- Hiippala, K.; Jouhten, H.; Ronkainen, A.; Hartikainen, A.; Kainulainen, V.; Jalanka, J.; Satokari, R. The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation. Nutrients 2018, 10, 988. [Google Scholar] [CrossRef]
- Cervantes-Barragan, L.; Chai, J.N.; Tianero, M.D.; Di Luccia, B.; Ahern, P.P.; Merriman, J.; Cortez, V.S.; Caparon, M.G.; Donia, M.S.; Gilfillan, S.; et al. Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells. Science 2017, 357, 806–810. [Google Scholar] [CrossRef]
- Sender, R.; Fuchs, S.; Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016, 14, e1002533. [Google Scholar] [CrossRef]
- Hollister, E.B.; Gao, C.; Versalovic, J. Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology 2014, 146, 1449–1458. [Google Scholar] [CrossRef]
- Doré, J.; Simrén, M.; Buttle, L.; Guarner, F. Hot topics in gut microbiota. United Eur. Gastroenterol. J. 2013, 1, 311–318. [Google Scholar] [CrossRef]
- Hillman, E.T.; Lu, H.; Yao, T.; Nakatsu, C.H. Microbial Ecology along the Gastrointestinal Tract. Microbes Environ. 2017, 32, 300–313. [Google Scholar] [CrossRef]
- Adak, A.; Khan, M.R. An insight into gut microbiota and its functionalities. Cell Mol. Life Sci. 2019, 76, 473–493. [Google Scholar] [CrossRef]
- Conlon, M.A.; Bird, A.R. The impact of diet and lifestyle on gut microbiota and human health. Nutrients 2014, 7, 17–44. [Google Scholar] [CrossRef]
- Gilbert, J.A.; Blaser, M.J.; Caporaso, J.G.; Jansson, J.K.; Lynch, S.V.; Knight, R. Current understanding of the human microbiome. Nat. Med. 2018, 24, 392–400. [Google Scholar] [CrossRef]
- Pinchera, B.; Moriello, N.S.; Buonomo, A.R.; Zappulo, E.; Viceconte, G.; Villari, R.; Gentile, I. Microbiota and hepatitis C virus in the era of direct-acting antiviral agents. Microb. Pathog. 2023, 175, 105968. [Google Scholar] [CrossRef]
- Ohtani, N.; Kawada, N. Role of the Gut-Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship. Hepatol. Commun. 2019, 3, 456–470. [Google Scholar] [CrossRef]
- Oliphant, K.; Allen-Vercoe, E. Macronutrient metabolism by the human gut microbiome: Major fermentation by-products and their impact on host health. Microbiome 2019, 7, 91. [Google Scholar] [CrossRef]
- Albillos, A.; de Gottardi, A.; Rescigno, M. The gut-liver axis in liver disease: Pathophysiological basis for therapy. J. Hepatol. 2020, 72, 558–577. [Google Scholar] [CrossRef]
- Round, J.L.; Mazmanian, S.K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 2009, 9, 313–323. [Google Scholar] [CrossRef]
- Wiest, R.; Albillos, A.; Trauner, M.; Bajaj, J.S.; Jalan, R. Targeting the gut-liver axis in liver disease. J. Hepatol. 2017, 67, 1084–1103. [Google Scholar] [CrossRef]
- Simbrunner, B.; Mandorfer, M.; Trauner, M.; Reiberger, T. Gut-liver axis signaling in portal hypertension. World J. Gastroenterol. 2019, 25, 5897–5917. [Google Scholar] [CrossRef]
- Guo, X.; Okpara, E.S.; Hu, W.; Yan, C.; Wang, Y.; Liang, Q.; Chiang, J.Y.L.; Han, S. Interactive Relationships between Intestinal Flora and Bile Acids. Int. J. Mol. Sci. 2022, 23, 8343. [Google Scholar] [CrossRef]
- Li, S.; Han, W.; He, Q.; Zhang, W.; Zhang, Y. Relationship between Intestinal Microflora and Hepatocellular Cancer Based on Gut-Liver Axis Theory. Contrast Media Mol. Imaging 2022, 2022, 6533628. [Google Scholar] [CrossRef]
- Tranah, T.H.; Edwards, L.A.; Schnabl, B.; Shawcross, D.L. Targeting the gut-liver-immune axis to treat cirrhosis. Gut 2021, 70, 982–994. [Google Scholar] [CrossRef]
- Odenwald, M.A.; Turner, J.R. The intestinal epithelial barrier: A therapeutic target? Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 9–21. [Google Scholar] [CrossRef]
- Marchiando, A.M.; Graham, W.V.; Turner, J.R. Epithelial barriers in homeostasis and disease. Annu. Rev. Pathol. 2010, 5, 119–144. [Google Scholar] [CrossRef]
- Van Itallie, C.M.; Anderson, J.M. Architecture of tight junctions and principles of molecular composition. Semin. Cell Dev. Biol. 2014, 36, 157–165. [Google Scholar] [CrossRef]
- Luissint, A.C.; Parkos, C.A.; Nusrat, A. Inflammation and the Intestinal Barrier: Leukocyte-Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair. Gastroenterology 2016, 151, 616–632. [Google Scholar] [CrossRef]
- Raleigh, D.R.; Marchiando, A.M.; Zhang, Y.; Shen, L.; Sasaki, H.; Wang, Y.; Long, M.; Turner, J.R. Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions. Mol. Biol. Cell. 2010, 21, 1200–1213. [Google Scholar] [CrossRef]
- Mineta, K.; Yamamoto, Y.; Yamazaki, Y.; Tanaka, H.; Tada, Y.; Saito, K.; Tamura, A.; Igarashi, M.; Endo, T.; Takeuchi, K.; et al. Predicted expansion of the claudin multigene family. FEBS Lett. 2011, 585, 606–612. [Google Scholar] [CrossRef]
- Monteiro, A.C.; Sumagin, R.; Rankin, C.R.; Leoni, G.; Mina, M.J.; Reiter, D.M.; Stehle, T.; Dermody, T.S.; Schaefer, S.A.; Hall, R.A.; et al. JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Mol. Biol. Cell. 2013, 24, 2849–2860. [Google Scholar] [CrossRef]
- Severson, E.A.; Parkos, C.A. Mechanisms of outside-in signaling at the tight junction by junctional adhesion molecule A. Ann. N. Y. Acad. Sci. 2009, 1165, 10–18. [Google Scholar] [CrossRef]
- Mandell, K.J.; Babbin, B.A.; Nusrat, A.; Parkos, C.A. Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on beta1 integrins and Rap1 activity. J. Biol. Chem. 2005, 280, 11665–11674. [Google Scholar] [CrossRef]
- Spadoni, I.; Fornasa, G.; Rescigno, M. Organ-specific protection mediated by cooperation between vascular and epithelial barriers. Nat. Rev. Immunol. 2017, 17, 761–773. [Google Scholar] [CrossRef]
- Spadoni, I.; Zagato, E.; Bertocchi, A.; Paolinelli, R.; Hot, E.; Di Sabatino, A.; Caprioli, F.; Bottiglieri, L.; Oldani, A.; Viale, G.; et al. A gut-vascular barrier controls the systemic dissemination of bacteria. Science 2015, 350, 830–834. [Google Scholar] [CrossRef]
- von Olshausen, G.; Quasdorff, M.; Bester, R.; Arzberger, S.; Ko, C.; van de Klundert, M.; Zhang, K.; Odenthal, M.; Ringelhan, M.; Niessen, C.M.; et al. Hepatitis B virus promotes β-catenin-signalling and disassembly of adherens junctions in a Src kinase dependent fashion. Oncotarget 2018, 9, 33947–33960. [Google Scholar] [CrossRef]
- Mowat, A.M.; Agace, W.W. Regional specialization within the intestinal immune system. Nat. Rev. Immunol. 2014, 14, 667–685. [Google Scholar] [CrossRef]
- Chieppa, M.; Rescigno, M.; Huang, A.Y.; Germain, R.N. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med. 2006, 203, 2841–2852. [Google Scholar] [CrossRef]
- Niess, J.H.; Brand, S.; Gu, X.; Landsman, L.; Jung, S.; McCormick, B.A.; Vyas, J.M.; Boes, M.; Ploegh, H.L.; Fox, J.G.; et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 2005, 307, 254–258. [Google Scholar] [CrossRef]
- Ismail, A.S.; Severson, K.M.; Vaishnava, S.; Behrendt, C.L.; Yu, X.; Benjamin, J.L.; Ruhn, K.A.; Hou, B.; DeFranco, A.L.; Yarovinsky, F.; et al. Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. Proc. Natl. Acad. Sci. USA 2011, 108, 8743–8748. [Google Scholar] [CrossRef]
- McDonald, B.D.; Jabri, B.; Bendelac, A. Diverse developmental pathways of intestinal intraepithelial lymphocytes. Nat. Rev. Immunol. 2018, 18, 514–525. [Google Scholar] [CrossRef]
- Mazzini, E.; Massimiliano, L.; Penna, G.; Rescigno, M. Oral tolerance can be established via gap junction transfer of fed antigens from CX3CR1+ macrophages to CD103+ dendritic cells. Immunity 2014, 40, 248–261. [Google Scholar] [CrossRef]
- Brennan, P.J.; Brigl, M.; Brenner, M.B. Invariant natural killer T cells: An innate activation scheme linked to diverse effector functions. Nat. Rev. Immunol. 2013, 13, 101–117. [Google Scholar] [CrossRef]
- Kjer-Nielsen, L.; Patel, O.; Corbett, A.J.; Le Nours, J.; Meehan, B.; Liu, L.; Bhati, M.; Chen, Z.; Kostenko, L.; Reantragoon, R.; et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 2012, 491, 717–723. [Google Scholar] [CrossRef]
- Dias, J.; Leeansyah, E.; Sandberg, J.K. Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines. Proc. Natl. Acad. Sci. USA 2017, 114, E5434–E5443. [Google Scholar] [CrossRef]
- Atarashi, K.; Tanoue, T.; Ando, M.; Kamada, N.; Nagano, Y.; Narushima, S.; Suda, W.; Imaoka, A.; Setoyama, H.; Nagamori, T.; et al. Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells. Cell 2015, 163, 367–380. [Google Scholar] [CrossRef]
- Ivanov, I.I.; Atarashi, K.; Manel, N.; Brodie, E.L.; Shima, T.; Karaoz, U.; Wei, D.; Goldfarb, K.C.; Santee, C.A.; Lynch, S.V.; et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009, 139, 485–498. [Google Scholar] [CrossRef]
- Sharma, A.; Rudra, D. Emerging Functions of Regulatory T Cells in Tissue Homeostasis. Front. Immunol. 2018, 9, 883. [Google Scholar] [CrossRef]
- Sandquist, I.; Kolls, J. Update on regulation and effector functions of Th17 cells. F1000Research 2018, 7, 205. [Google Scholar] [CrossRef]
- Tsilingiri, K.; Rescigno, M. Postbiotics: What else? Benef. Microbes. 2013, 4, 101–107. [Google Scholar] [CrossRef]
- Mosca, F.; Gianni, M.L.; Rescigno, M. Can Postbiotics Represent a New Strategy for NEC? Adv. Exp. Med. Biol. 2019, 1125, 37–45. [Google Scholar]
- Rivière, A.; Selak, M.; Lantin, D.; Leroy, F.; De Vuyst, L. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut. Front. Microbiol. 2016, 7, 979. [Google Scholar] [CrossRef]
- Yaku, K.; Enami, Y.; Kurajyo, C.; Matsui-Yuasa, I.; Konishi, Y.; Kojima-Yuasa, A. The enhancement of phase 2 enzyme activities by sodium butyrate in normal intestinal epithelial cells is associated with Nrf2 and p53. Mol. Cell Biochem. 2012, 370, 7–14. [Google Scholar] [CrossRef]
- Ziegler, K.; Kerimi, A.; Poquet, L.; Williamson, G. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4). Arch. Biochem. Biophys. 2016, 599, 3–12. [Google Scholar] [CrossRef]
- Morrison, D.J.; Preston, T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 2016, 7, 189–200. [Google Scholar] [CrossRef]
- Schulthess, J.; Pandey, S.; Capitani, M.; Rue-Albrecht, K.C.; Arnold, I.; Franchini, F.; Chomka, A.; Ilott, N.E.; Johnston, D.G.W.; Pires, E.; et al. The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages. Immunity 2019, 50, 432–445.e7. [Google Scholar] [CrossRef]
- Park, J.; Kim, M.; Kang, S.G.; Jannasch, A.H.; Cooper, B.; Patterson, J.; Kim, C.H. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 2015, 8, 80–93. [Google Scholar] [CrossRef]
- Bachem, A.; Makhlouf, C.; Binger, K.J.; de Souza, D.P.; Tull, D.; Hochheiser, K.; Whitney, P.G.; Fernandez-Ruiz, D.; Dähling, S.; Kastenmüller, W.; et al. Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8+ T Cells. Immunity 2019, 51, 285–297.e5. [Google Scholar] [CrossRef]
- Park, J.H.; Eberl, G. Type 3 regulatory T cells at the interface of symbiosis. J. Microbiol. 2018, 56, 163–171. [Google Scholar] [CrossRef]
- Sun, S.; Luo, L.; Liang, W.; Yin, Q.; Guo, J.; Rush, A.M.; Lv, Z.; Liang, Q.; Fischbach, M.A.; Sonnenburg, J.L.; et al. Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade. Proc. Natl. Acad. Sci. USA 2020, 117, 27509–27515. [Google Scholar] [CrossRef]
- Alessandri, G.; Ossiprandi, M.C.; MacSharry, J.; van Sinderen, D.; Ventura, M. Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System. Front. Immunol. 2019, 10, 2348. [Google Scholar] [CrossRef]
- Elshaghabee, F.M.; Bockelmann, W.; Meske, D.; de Vrese, M.; Walte, H.G.; Schrezenmeir, J.; Heller, K.J. Ethanol Production by Selected Intestinal Microorganisms and Lactic Acid Bacteria Growing under Different Nutritional Conditions. Front. Microbiol. 2016, 7, 47. [Google Scholar] [CrossRef]
- Zhu, L.; Baker, S.S.; Gill, C.; Liu, W.; Alkhouri, R.; Baker, R.D.; Gill, S.R. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH. Hepatology 2013, 57, 601–609. [Google Scholar] [CrossRef]
- Barreau, F.; Hugot, J.P. Intestinal barrier dysfunction triggered by invasive bacteria. Curr. Opin. Microbiol. 2014, 17, 91–98. [Google Scholar] [CrossRef]
- Rakoff-Nahoum, S.; Paglino, J.; Eslami-Varzaneh, F.; Edberg, S.; Medzhitov, R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004, 118, 229–241. [Google Scholar] [CrossRef]
- Cario, E.; Gerken, G.; Podolsky, D.K. Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 2004, 127, 224–238. [Google Scholar] [CrossRef]
- Li, X.; Wang, C.; Nie, J.; Lv, D.; Wang, T.; Xu, Y. Toll-like receptor 4 increases intestinal permeability through up-regulation of membrane PKC activity in alcoholic steatohepatitis. Alcohol 2013, 47, 459–465. [Google Scholar] [CrossRef]
- Sharma, R.; Young, C.; Neu, J. Molecular modulation of intestinal epithelial barrier: Contribution of microbiota. J. Biomed. Biotechnol. 2010, 2010, 305879. [Google Scholar] [CrossRef]
- Takeuchi, O.; Akira, S. Pattern recognition receptors and inflammation. Cell 2010, 140, 805–820. [Google Scholar] [CrossRef]
- Ignacio, A.; Morales, C.I.; Câmara, N.O.; Almeida, R.R. Innate Sensing of the Gut Microbiota: Modulation of Inflammatory and Autoimmune Diseases. Front. Immunol. 2016, 7, 54. [Google Scholar] [CrossRef]
- Wu, J.; Meng, Z.; Jiang, M.; Zhang, E.; Trippler, M.; Broering, R.; Bucchi, A.; Krux, F.; Dittmer, U.; Yang, D.; et al. Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific. Immunology 2010, 129, 363–374. [Google Scholar] [CrossRef]
- Seki, E.; Brenner, D.A. Toll-like receptors and adaptor molecules in liver disease: Update. Hepatology 2008, 48, 322–335. [Google Scholar] [CrossRef]
- Miyake, Y.; Yamamoto, K. Role of gut microbiota in liver diseases. Hepatol. Res. 2013, 43, 139–146. [Google Scholar] [CrossRef]
- Seki, E.; Tsutsui, H.; Nakano, H.; Tsuji, N.; Hoshino, K.; Adachi, O.; Adachi, K.; Futatsugi, S.; Kuida, K.; Takeuchi, O.; et al. Lipopolysaccharide-induced IL-18 secretion from murine Kupffer cells independently of myeloid differentiation factor 88 that is critically involved in induction of production of IL-12 and IL-1beta. J. Immunol. 2001, 166, 2651–2657. [Google Scholar] [CrossRef]
- Rogier, R.; Koenders, M.I.; Abdollahi-Roodsaz, S. Toll-like receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis. J. Immunol. Res. 2015, 2015, 527696. [Google Scholar] [CrossRef]
- Pasare, C.; Medzhitov, R. Toll-like receptors and acquired immunity. Semin. Immunol. 2004, 16, 23–26. [Google Scholar] [CrossRef]
- Bonnert, T.P.; Garka, K.E.; Parnet, P.; Sonoda, G.; Testa, J.R.; Sims, J.E. The cloning and characterization of human MyD88: A member of an IL-1 receptor related family. FEBS Lett. 1997, 402, 81–84. [Google Scholar] [CrossRef]
- Yamamoto, M.; Takeda, K. Current views of toll-like receptor signaling pathways. Gastroenterol. Res. Pract. 2010, 2010, 240365. [Google Scholar] [CrossRef]
- Agrawal, S.; Agrawal, A.; Doughty, B.; Gerwitz, A.; Blenis, J.; Van Dyke, T.; Pulendran, B. Cutting edge: Different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J. Immunol. 2003, 171, 4984–4989. [Google Scholar] [CrossRef]
- Kattah, M.G.; Wong, M.T.; Yocum, M.D.; Utz, P.J. Cytokines secreted in response to Toll-like receptor ligand stimulation modulate differentiation of human Th17 cells. Arthritis Rheum. 2008, 58, 1619–1629. [Google Scholar] [CrossRef]
- Dillon, S.; Agrawal, A.; Van Dyke, T.; Landreth, G.; McCauley, L.; Koh, A.; Maliszewski, C.; Akira, S.; Pulendran, B. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J. Immunol. 2004, 172, 4733–4743. [Google Scholar] [CrossRef]
- Chow, J.C.; Young, D.W.; Golenbock, D.T.; Christ, W.J.; Gusovsky, F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J. Biol. Chem. 1999, 274, 10689–10692. [Google Scholar] [CrossRef]
- Bauer, S.; Kirschning, C.J.; Häcker, H.; Redecke, V.; Hausmann, S.; Akira, S.; Wagner, H.; Lipford, G.B. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl. Acad. Sci. USA 2001, 98, 9237–9242. [Google Scholar] [CrossRef]
- Dolganiuc, A.; Oak, S.; Kodys, K.; Golenbock, D.T.; Finberg, R.W.; Kurt-Jones, E.; Szabo, G. Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation. Gastroenterology 2004, 127, 1513–1524. [Google Scholar] [CrossRef]
- Wang, B.; Trippler, M.; Pei, R.; Lu, M.; Broering, R.; Gerken, G.; Schlaak, J.F. Toll-like receptor activated human and murine hepatic stellate cells are potent regulators of hepatitis C virus replication. J. Hepatol. 2009, 51, 1037–1045. [Google Scholar] [CrossRef]
- Seki, E.; De Minicis, S.; Osterreicher, C.H.; Kluwe, J.; Osawa, Y.; Brenner, D.A.; Schwabe, R.F. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat. Med. 2007, 13, 1324–1332. [Google Scholar] [CrossRef]
- Isayama, F.; Hines, I.N.; Kremer, M.; Milton, R.J.; Byrd, C.L.; Perry, A.W.; McKim, S.E.; Parsons, C.; Rippe, R.A.; Wheeler, M.D. LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 290, G1318–G1328. [Google Scholar] [CrossRef]
- Gäbele, E.; Mühlbauer, M.; Dorn, C.; Weiss, T.S.; Froh, M.; Schnabl, B.; Wiest, R.; Schölmerich, J.; Obermeier, F.; Hellerbrand, C. Role of TLR9 in hepatic stellate cells and experimental liver fibrosis. Biochem. Biophys. Res. Commun. 2008, 376, 271–276. [Google Scholar] [CrossRef]
- Hartmann, P.; Haimerl, M.; Mazagova, M.; Brenner, D.A.; Schnabl, B. Toll-like receptor 2-mediated intestinal injury and enteric tumor necrosis factor receptor I contribute to liver fibrosis in mice. Gastroenterology 2012, 143, 1330–1340.e1. [Google Scholar] [CrossRef]
- Seki, E.; Schnabl, B. Role of innate immunity and the microbiota in liver fibrosis: Crosstalk between the liver and gut. J. Physiol. 2012, 590, 447–458. [Google Scholar] [CrossRef]
- Czaja, A.J. Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis. World J. Gastroenterol. 2016, 22, 9257–9278. [Google Scholar] [CrossRef]
- Chopyk, D.M.; Grakoui, A. Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders. Gastroenterology 2020, 159, 849–863. [Google Scholar] [CrossRef]
- Agus, A.; Planchais, J.; Sokol, H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018, 23, 716–724. [Google Scholar] [CrossRef]
- Zelante, T.; Iannitti, R.G.; Cunha, C.; De Luca, A.; Giovannini, G.; Pieraccini, G.; Zecchi, R.; D’Angelo, C.; Massi-Benedetti, C.; Fallarino, F.; et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 2013, 39, 372–385. [Google Scholar] [CrossRef]
- Ma, Z.; Cao, Q.; Xiong, Y.; Zhang, E.; Lu, M. Interaction between Hepatitis B Virus and Toll-Like Receptors: Current Status and Potential Therapeutic Use for Chronic Hepatitis B. Vaccines 2018, 6, 6. [Google Scholar] [CrossRef]
- Ashfaq, U.A.; Iqbal, M.S.; Khaliq, S. Role of Toll-Like Receptors in Hepatitis C Virus Pathogenesis and Treatment. Crit. Rev. Eukaryot. Gene Expr. 2016, 26, 353–362. [Google Scholar] [CrossRef]
- Chen, B.; Chen, H.; Shu, X.; Yin, Y.; Li, J.; Qin, J.; Chen, L.; Peng, K.; Xu, F.; Gu, W.; et al. Presence of Segmented Filamentous Bacteria in Human Children and Its Potential Role in the Modulation of Human Gut Immunity. Front. Microbiol. 2018, 9, 1403. [Google Scholar] [CrossRef]
- Blacher, E.; Levy, M.; Tatirovsky, E.; Elinav, E. Microbiome-Modulated Metabolites at the Interface of Host Immunity. J. Immunol. 2017, 198, 572–580. [Google Scholar] [CrossRef]
- Levy, M.; Blacher, E.; Elinav, E. Microbiome, metabolites and host immunity. Curr. Opin. Microbiol. 2017, 35, 8–15. [Google Scholar] [CrossRef]
- Johansson, M.E. Fast renewal of the distal colonic mucus layers by the surface goblet cells as measured by in vivo labeling of mucin glycoproteins. PLoS ONE 2012, 7, e41009. [Google Scholar] [CrossRef]
- Bergström, J.H.; Birchenough, G.M.; Katona, G.; Schroeder, B.O.; Schütte, A.; Ermund, A.; Johansson, M.E.; Hansson, G.C. Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16. Proc. Natl. Acad. Sci. USA 2016, 113, 13833–13838. [Google Scholar] [CrossRef]
- Johansson, M.E.; Ambort, D.; Pelaseyed, T.; Schütte, A.; Gustafsson, J.K.; Ermund, A.; Subramani, D.B.; Holmén-Larsson, J.M.; Thomsson, K.A.; Bergström, J.H.; et al. Composition and functional role of the mucus layers in the intestine. Cell Mol. Life Sci. 2011, 68, 3635–3641. [Google Scholar] [CrossRef]
- Gibbins, H.L.; Proctor, G.B.; Yakubov, G.E.; Wilson, S.; Carpenter, G.H. SIgA binding to mucosal surfaces is mediated by mucin-mucin interactions. PLoS ONE 2015, 10, e0119677. [Google Scholar] [CrossRef]
- Jakobsson, H.E.; Rodríguez-Piñeiro, A.M.; Schütte, A.; Ermund, A.; Boysen, P.; Bemark, M.; Sommer, F.; Bäckhed, F.; Hansson, G.C.; Johansson, M.E. The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep. 2015, 16, 164–177. [Google Scholar] [CrossRef]
- Birchenough, G.M.; Nyström, E.E.; Johansson, M.E.; Hansson, G.C. A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science 2016, 352, 1535–1542. [Google Scholar] [CrossRef] [PubMed]
- Derrien, M.; Van Baarlen, P.; Hooiveld, G.; Norin, E.; Müller, M.; de Vos, W.M. Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila. Front. Microbiol. 2011, 2, 166. [Google Scholar] [CrossRef] [PubMed]
- Abreu, M.T. Toll-like receptor signalling in the intestinal epithelium: How bacterial recognition shapes intestinal function. Nat. Rev. Immunol. 2010, 10, 131–144. [Google Scholar] [CrossRef] [PubMed]
- Gallo, R.L.; Hooper, L.V. Epithelial antimicrobial defence of the skin and intestine. Nat. Rev. Immunol. 2012, 12, 503–516. [Google Scholar] [CrossRef] [PubMed]
- Nakamura, K.; Sakuragi, N.; Takakuwa, A.; Ayabe, T. Paneth cell α-defensins and enteric microbiota in health and disease. Biosci. Microbiota Food Health 2016, 35, 57–67. [Google Scholar] [CrossRef]
- Mantis, N.J.; Rol, N.; Corthésy, B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011, 4, 603–611. [Google Scholar] [CrossRef]
- Donaldson, G.P.; Ladinsky, M.S.; Yu, K.B.; Sanders, J.G.; Yoo, B.B.; Chou, W.C.; Conner, M.E.; Earl, A.M.; Knight, R.; Bjorkman, P.J.; et al. Gut microbiota utilize immunoglobulin A for mucosal colonization. Science 2018, 360, 795–800. [Google Scholar] [CrossRef]
- Macpherson, A.J.; Geuking, M.B.; McCoy, K.D. Homeland security: IgA immunity at the frontiers of the body. Trends Immunol. 2012, 33, 160–167. [Google Scholar] [CrossRef]
- Chairatana, P.; Nolan, E.M. Defensins, lectins, mucins, and secretory immunoglobulin A: Microbe-binding biomolecules that contribute to mucosal immunity in the human gut. Crit. Rev. Biochem. Mol. Biol. 2017, 52, 45–56. [Google Scholar] [CrossRef]
- Mukherjee, S.; Hooper, L.V. Antimicrobial defense of the intestine. Immunity 2015, 42, 28–39. [Google Scholar] [CrossRef]
- Leclercq, S.; Cani, P.D.; Neyrinck, A.M.; Stärkel, P.; Jamar, F.; Mikolajczak, M.; Delzenne, N.M.; de Timary, P. Role of intestinal permeability and inflammation in the biological and behavioral control of alcohol-dependent subjects. Brain Behav. Immun. 2012, 26, 911–918. [Google Scholar] [CrossRef] [PubMed]
- Cresci, G.A.; Glueck, B.; McMullen, M.R.; Xin, W.; Allende, D.; Nagy, L.E. Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury. J. Gastroenterol. Hepatol. 2017, 32, 1587–1597. [Google Scholar] [CrossRef]
- Boursi, B.; Mamtani, R.; Haynes, K.; Yang, Y.X. The effect of past antibiotic exposure on diabetes risk. Eur. J. Endocrinol. 2015, 172, 639–648. [Google Scholar] [CrossRef] [PubMed]
- Kozyrskyj, A.L.; Ernst, P.; Becker, A.B. Increased risk of childhood asthma from antibiotic use in early life. Chest 2007, 131, 1753–1759. [Google Scholar] [CrossRef] [PubMed]
- Francino, M.P. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front. Microbiol. 2016, 6, 1543. [Google Scholar] [CrossRef] [PubMed]
- Mårild, K.; Ye, W.; Lebwohl, B.; Green, P.H.; Blaser, M.J.; Card, T.; Ludvigsson, J.F. Antibiotic exposure and the development of coeliac disease: A nationwide case-control study. BMC Gastroenterol. 2013, 13, 109. [Google Scholar] [CrossRef] [PubMed]
- Petersen, C.; Round, J.L. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 2014, 16, 1024–1033. [Google Scholar] [CrossRef]
- Csak, T.; Ganz, M.; Pespisa, J.; Kodys, K.; Dolganiuc, A.; Szabo, G. Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells. Hepatology 2011, 54, 133–144. [Google Scholar] [CrossRef]
- Uesugi, T.; Froh, M.; Arteel, G.E.; Bradford, B.U.; Thurman, R.G. Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. Hepatology 2001, 34, 101–108. [Google Scholar] [CrossRef]
- Anand, G.; Zarrinpar, A.; Loomba, R. Targeting Dysbiosis for the Treatment of Liver Disease. Semin. Liver Dis. 2016, 36, 37–47. [Google Scholar] [CrossRef]
- Stärkel, P.; Schnabl, B. Bidirectional Communication between Liver and Gut during Alcoholic Liver Disease. Semin. Liver Dis. 2016, 36, 331–339. [Google Scholar] [CrossRef] [PubMed]
- Tripathi, A.; Debelius, J.; Brenner, D.A.; Karin, M.; Loomba, R.; Schnabl, B.; Knight, R. The gut-liver axis and the intersection with the microbiome. Nat. Rev. Gastroenterol. Hepatol. 2018, 15, 397–411. [Google Scholar] [CrossRef] [PubMed]
- Wiest, R.; Garcia-Tsao, G. Bacterial translocation (BT) in cirrhosis. Hepatology 2005, 41, 422–433. [Google Scholar] [CrossRef] [PubMed]
- Mehal, W.Z. The Gordian Knot of dysbiosis, obesity and NAFLD. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 637–644. [Google Scholar] [CrossRef] [PubMed]
- Bourriaud, C.; Robins, R.J.; Martin, L.; Kozlowski, F.; Tenailleau, E.; Cherbut, C.; Michel, C. Lactate is mainly fermented to butyrate by human intestinal microfloras but inter-individual variation is evident. J. Appl. Microbiol. 2005, 99, 201–212. [Google Scholar] [CrossRef] [PubMed]
- Wahlström, A.; Sayin, S.I.; Marschall, H.U.; Bäckhed, F. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016, 24, 41–50. [Google Scholar] [CrossRef]
- de Aguiar Vallim, T.Q.; Tarling, E.J.; Edwards, P.A. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013, 17, 657–669. [Google Scholar] [CrossRef]
- Staley, C.; Weingarden, A.R.; Khoruts, A.; Sadowsky, M.J. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl. Microbiol. Biotechnol. 2017, 101, 47–64. [Google Scholar] [CrossRef]
- Lachar, J.; Bajaj, J.S. Changes in the Microbiome in Cirrhosis and Relationship to Complications: Hepatic Encephalopathy, Spontaneous Bacterial Peritonitis, and Sepsis. Semin. Liver Dis. 2016, 36, 327–330. [Google Scholar] [CrossRef]
- Chiang, J.Y.L.; Ferrell, J.M. Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy. Am. J. Physiol. Gastrointest. Liver Physiol. 2020, 318, G554–G573. [Google Scholar] [CrossRef]
- Copple, B.L.; Li, T. Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules. Pharmacol. Res. 2016, 104, 9–21. [Google Scholar] [CrossRef] [PubMed]
- Stofan, M.; Guo, G.L. Bile Acids and FXR: Novel Targets for Liver Diseases. Front. Med. 2020, 7, 544. [Google Scholar] [CrossRef]
- Zhu, F.; Zheng, S.; Zhao, M.; Shi, F.; Zheng, L.; Wang, H. The regulatory role of bile acid microbiota in the progression of liver cirrhosis. Front. Pharmacol. 2023, 14, 1214685. [Google Scholar] [CrossRef]
- Zarrinpar, A.; Loomba, R. Review article: The emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 2012, 36, 909–921. [Google Scholar] [CrossRef]
- Sayin, S.I.; Wahlström, A.; Felin, J.; Jäntti, S.; Marschall, H.U.; Bamberg, K.; Angelin, B.; Hyötyläinen, T.; Orešič, M.; Bäckhed, F. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013, 17, 225–235. [Google Scholar] [CrossRef]
- Inagaki, T.; Moschetta, A.; Lee, Y.K.; Peng, L.; Zhao, G.; Downes, M.; Yu, R.T.; Shelton, J.M.; Richardson, J.A.; Repa, J.J.; et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl. Acad. Sci. USA 2006, 103, 3920–3925. [Google Scholar] [CrossRef]
- Parséus, A.; Sommer, N.; Sommer, F.; Caesar, R.; Molinaro, A.; Ståhlman, M.; Greiner, T.U.; Perkins, R.; Bäckhed, F. Microbiota-induced obesity requires farnesoid X receptor. Gut 2017, 66, 429–437. [Google Scholar] [CrossRef] [PubMed]
- Gadaleta, R.M.; van Erpecum, K.J.; Oldenburg, B.; Willemsen, E.C.; Renooij, W.; Murzilli, S.; Klomp, L.W.; Siersema, P.D.; Schipper, M.E.; Danese, S.; et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut 2011, 60, 463–472. [Google Scholar] [CrossRef]
- Mouries, J.; Brescia, P.; Silvestri, A.; Spadoni, I.; Sorribas, M.; Wiest, R.; Mileti, E.; Galbiati, M.; Invernizzi, P.; Adorini, L.; et al. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J. Hepatol. 2019, 71, 1216–1228. [Google Scholar] [CrossRef]
- Pols, T.W.; Noriega, L.G.; Nomura, M.; Auwerx, J.; Schoonjans, K. The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation. J. Hepatol. 2011, 54, 1263–1272. [Google Scholar] [CrossRef] [PubMed]
- Broeders, E.P.; Nascimento, E.B.; Havekes, B.; Brans, B.; Roumans, K.H.; Tailleux, A.; Schaart, G.; Kouach, M.; Charton, J.; Deprez, B.; et al. The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity. Cell Metab. 2015, 22, 418–426. [Google Scholar] [CrossRef]
- Thomas, C.; Gioiello, A.; Noriega, L.; Strehle, A.; Oury, J.; Rizzo, G.; Macchiarulo, A.; Yamamoto, H.; Mataki, C.; Pruzanski, M.; et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009, 10, 167–177. [Google Scholar] [CrossRef]
- Hsu, Y.C.; Huang, D.Q.; Nguyen, M.H. Global burden of hepatitis B virus: Current status, missed opportunities and a call for action. Nat. Rev. Gastroenterol. Hepatol. 2023, 20, 524–537. [Google Scholar] [CrossRef]
- Iannacone, M.; Guidotti, L.G. Immunobiology and pathogenesis of hepatitis B virus infection. Nat. Rev. Immunol. 2022, 22, 19–32. [Google Scholar] [CrossRef]
- Chen, Z.; Xie, Y.; Zhou, F.; Zhang, B.; Wu, J.; Yang, L.; Xu, S.; Stedtfeld, R.; Chen, Q.; Liu, J.; et al. Featured Gut Microbiomes Associated With the Progression of Chronic Hepatitis B Disease. Front. Microbiol. 2020, 11, 383. [Google Scholar] [CrossRef]
- Zhu, Q.; Xia, P.; Zhou, X.; Li, X.; Guo, W.; Zhu, B.; Zheng, X.; Wang, B.; Yang, D.; Wang, J. Hepatitis B Virus Infection Alters Gut Microbiota Composition in Mice. Front. Cell Infect. Microbiol. 2019, 9, 377, Erratum in Front. Cell Infect. Microbiol. 2020, 10, 490. [Google Scholar] [CrossRef]
- Li, X.; Wu, S.; Du, Y.; Yang, L.; Li, Y.; Hong, B. Entecavir therapy reverses gut microbiota dysbiosis induced by hepatitis B virus infection in a mouse model. Int. J. Antimicrob. Agents. 2020, 56, 106000. [Google Scholar] [CrossRef]
- Wang, J.; Wang, Y.; Zhang, X.; Liu, J.; Zhang, Q.; Zhao, Y.; Peng, J.; Feng, Q.; Dai, J.; Sun, S.; et al. Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum Metabolites in Chronic Hepatitis B Patients. Front. Microbiol. 2017, 8, 2222. [Google Scholar] [CrossRef]
- Chen, Y.; Yang, F.; Lu, H.; Wang, B.; Chen, Y.; Lei, D.; Wang, Y.; Zhu, B.; Li, L. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 2011, 54, 562–572. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Chen, L.; Wang, H.; Cai, W.; Xie, Q. Modulation of bile acid profile by gut microbiota in chronic hepatitis B. J. Cell Mol. Med. 2020, 24, 2573–2581. [Google Scholar] [CrossRef] [PubMed]
- Sun, Z.; Huang, C.; Shi, Y.; Wang, R.; Fan, J.; Yu, Y.; Zhang, Z.; Zhu, K.; Li, M.; Ni, Q.; et al. Distinct Bile Acid Profiles in Patients With Chronic Hepatitis B Virus Infection Reveal Metabolic Interplay Between Host, Virus and Gut Microbiome. Front. Med. 2021, 8, 708495. [Google Scholar] [CrossRef] [PubMed]
- Joo, E.J.; Cheong, H.S.; Kwon, M.J.; Sohn, W.; Kim, H.N.; Cho, Y.K. Relationship between gut microbiome diversity and hepatitis B viral load in patients with chronic hepatitis B. Gut Pathog. 2021, 13, 65. [Google Scholar] [CrossRef] [PubMed]
- Sandler, N.G.; Koh, C.; Roque, A.; Eccleston, J.L.; Siegel, R.B.; Demino, M.; Kleiner, D.E.; Deeks, S.G.; Liang, T.J.; Heller, T.; et al. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology 2011, 141, 1220–1230.e1–3. [Google Scholar] [CrossRef] [PubMed]
- Yun, Y.; Chang, Y.; Kim, H.N.; Ryu, S.; Kwon, M.J.; Cho, Y.K.; Kim, H.L.; Cheong, H.S.; Joo, E.J. Alterations of the Gut Microbiome in Chronic Hepatitis B Virus Infection Associated with Alanine Aminotransferase Level. J. Clin. Med. 2019, 8, 173. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Zhao, R.; Shi, D.; Sun, S.; Ren, H.; Zhao, H.; Wu, W.; Jin, L.; Sheng, J.; Shi, Y. Characterization of the circulating microbiome in acute-on-chronic liver failure associated with hepatitis B. Liver Int. 2019, 39, 1207–1216. [Google Scholar] [CrossRef] [PubMed]
- Zeng, Y.; Chen, S.; Fu, Y.; Wu, W.; Chen, T.; Chen, J.; Yang, B.; Ou, Q. Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. J. Viral Hepat. 2020, 27, 143–155. [Google Scholar] [CrossRef] [PubMed]
- Lin, M.J.; Su, T.H.; Chen, C.C.; Wu, W.K.; Hsu, S.J.; Tseng, T.C.; Liao, S.H.; Hong, C.M.; Yang, H.C.; Liu, C.J.; et al. Diversity and composition of gut microbiota in healthy individuals and patients at different stages of hepatitis B virus-related liver disease. Gut Pathog. 2023, 15, 24. [Google Scholar] [CrossRef] [PubMed]
- Bailey, M.A.; Holscher, H.D. Microbiome-Mediated Effects of the Mediterranean Diet on Inflammation. Adv. Nutr. 2018, 9, 193–206. [Google Scholar] [CrossRef]
- Liu, Q.; Li, F.; Zhuang, Y.; Xu, J.; Wang, J.; Mao, X.; Zhang, Y.; Liu, X. Alteration in gut microbiota associated with hepatitis B and non-hepatitis virus related hepatocellular carcinoma. Gut Pathog. 2019, 11, 1. [Google Scholar] [CrossRef]
- Qin, N.; Yang, F.; Li, A.; Prifti, E.; Chen, Y.; Shao, L.; Guo, J.; Le Chatelier, E.; Yao, J.; Wu, L.; et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 2014, 513, 59–64. [Google Scholar] [CrossRef]
- Liu, Y.; Li, J.; Jin, Y.; Zhao, L.; Zhao, F.; Feng, J.; Li, A.; Wei, Y. Splenectomy Leads to Amelioration of Altered Gut Microbiota and Metabolome in Liver Cirrhosis Patients. Front. Microbiol. 2018, 9, 963. [Google Scholar] [CrossRef]
- Wei, X.; Yan, X.; Zou, D.; Yang, Z.; Wang, X.; Liu, W.; Wang, S.; Li, X.; Han, J.; Huang, L.; et al. Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach. BMC Gastroenterol. 2013, 13, 175. [Google Scholar] [CrossRef]
- Lu, H.; Wu, Z.; Xu, W.; Yang, J.; Chen, Y.; Li, L. Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients. Microb. Ecol. 2011, 61, 693–703. [Google Scholar] [CrossRef]
- Calgin, M.K.; Cetinkol, Y. Decreased levels of serum zonulin and copeptin in chronic Hepatitis-B patients. Pak. J. Med. Sci. 2019, 35, 847–851. [Google Scholar] [CrossRef]
- Wang, X.; Li, M.M.; Niu, Y.; Zhang, X.; Yin, J.B.; Zhao, C.J.; Wang, R.T. Serum Zonulin in HBV-Associated Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma. Dis. Markers 2019, 2019, 5945721. [Google Scholar] [CrossRef]
- Zheng, D.; Liwinski, T.; Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020, 30, 492–506. [Google Scholar] [CrossRef]
- Yang, X.A.; Lv, F.; Wang, R.; Chang, Y.; Zhao, Y.; Cui, X.; Li, H.; Yang, S.; Li, S.; Zhao, X.; et al. Potential role of intestinal microflora in disease progression among patients with different stages of Hepatitis B. Gut Pathog. 2020, 12, 50. [Google Scholar] [CrossRef]
- Ren, Z.; Li, A.; Jiang, J.; Zhou, L.; Yu, Z.; Lu, H.; Xie, H.; Chen, X.; Shao, L.; Zhang, R.; et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut 2019, 68, 1014–1023. [Google Scholar] [CrossRef]
- Zhao, Y.; Mao, Y.F.; Tang, Y.S.; Ni, M.Z.; Liu, Q.H.; Wang, Y.; Feng, Q.; Peng, J.H.; Hu, Y.Y. Altered oral microbiota in chronic hepatitis B patients with different tongue coatings. World J. Gastroenterol. 2018, 24, 3448–3461. [Google Scholar] [CrossRef]
- Li, R.; Yi, X.; Yang, J.; Zhu, Z.; Wang, Y.; Liu, X.; Huang, X.; Wan, Y.; Fu, X.; Shu, W.; et al. Gut Microbiome Signatures in the Progression of Hepatitis B Virus-Induced Liver Disease. Front. Microbiol. 2022, 13, 916061. [Google Scholar] [CrossRef]
- Lu, Y.X.; He, C.Z.; Wang, Y.X.; Ai, Z.S.; Liang, P.; Yang, C.Q. Effect of Entecavir on the Intestinal Microflora in Patients with Chronic Hepatitis B: A Controlled Cross-Sectional and Longitudinal Real-World Study. Infect. Dis. Ther. 2021, 10, 241–252. [Google Scholar] [CrossRef]
- Chen, B.; Huang, H.; Pan, C.Q. The role of gut microbiota in hepatitis B disease progression and treatment. J. Viral Hepat. 2022, 29, 94–106. [Google Scholar] [CrossRef]
- Li, Y.N.; Kang, N.L.; Jiang, J.J.; Zhu, Y.Y.; Liu, Y.R.; Zeng, D.W.; Wang, F. Gut microbiota of hepatitis B virus-infected patients in the immune-tolerant and immune-active phases and their implications in metabolite changes. World J. Gastroenterol. 2022, 28, 5188–5202. [Google Scholar] [CrossRef]
- Shu, W.; Shanjian, C.; Jinpiao, L.; Qishui, O. Gut microbiota dysbiosis in patients with hepatitis B virus-related cirrhosis. Ann. Hepatol. 2022, 27, 100676. [Google Scholar] [CrossRef]
- Gao, K.; Liu, L.; Wang, H. Advances in immunomodulation of microbial unmethylated CpG DNA on animal intestinal tract A review. Wei Sheng Wu Xue Bao 2015, 55, 543–550. [Google Scholar]
- Yang, R.; Xu, Y.; Dai, Z.; Lin, X.; Wang, H. The Immunologic Role of Gut Microbiota in Patients with Chronic HBV Infection. J. Immunol. Res. 2018, 2018, 2361963. [Google Scholar] [CrossRef]
- Yan, F.; Zhang, Q.; Shi, K.; Zhang, Y.; Zhu, B.; Bi, Y.; Wang, X. Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response. Front. Cell Infect. Microbiol. 2023, 13, 1152987. [Google Scholar] [CrossRef]
- Xu, D.; Huang, Y.; Wang, J. Gut microbiota modulate the immune effect against hepatitis B virus infection. Eur. J. Clin. Microbiol. Infect. Dis. 2015, 34, 2139–2147. [Google Scholar] [CrossRef]
- Chou, H.H.; Chien, W.H.; Wu, L.L.; Cheng, C.H.; Chung, C.H.; Horng, J.H.; Ni, Y.H.; Tseng, H.T.; Wu, D.; Lu, X.; et al. Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota. Proc. Natl. Acad. Sci. USA 2015, 112, 2175–2180. [Google Scholar] [CrossRef]
- Guo, W.; Zhou, X.; Li, X.; Zhu, Q.; Peng, J.; Zhu, B.; Zheng, X.; Lu, Y.; Yang, D.; Wang, B.; et al. Depletion of Gut Microbiota Impairs Gut Barrier Function and Antiviral Immune Defense in the Liver. Front. Immunol. 2021, 12, 636803. [Google Scholar] [CrossRef]
- Wu, T.; Li, F.; Chen, Y.; Wei, H.; Tian, Z.; Sun, C.; Sun, R. CD4+ T Cells Play a Critical Role in Microbiota-Maintained Anti-HBV Immunity in a Mouse Model. Front. Immunol. 2019, 10, 927. [Google Scholar] [CrossRef]
- Li, Y.; Zhong, S.; Jin, Z.; Ye, G.; Zhang, T.; Liu, Z.; Liu, Z.; Zeng, Z.; Li, Q.; Wang, Y.; et al. Peyer’s patch-involved gut microbiota facilitates anti-HBV immunity in mice. Virus Res. 2023, 331, 199129. [Google Scholar] [CrossRef]
- Zhou, W.; Luo, J.; Xie, X.; Yang, S.; Zhu, D.; Huang, H.; Yang, D.; Liu, J. Gut Microbiota Dysbiosis Strengthens Kupffer Cell-mediated Hepatitis B Virus Persistence through Inducing Endotoxemia in Mice. J. Clin. Transl. Hepatol. 2022, 10, 17–25. [Google Scholar] [CrossRef]
- Bu, Y.; Zhao, K.; Xu, Z.; Zheng, Y.; Hua, R.; Wu, C.; Zhu, C.; Xia, Y.; Cheng, X. Antibiotic-induced gut bacteria depletion has no effect on HBV replication in HBV immune tolerance mouse model. Virol. Sin. 2023, 38, 335–343. [Google Scholar] [CrossRef]
- Sun, X.; Pan, C.Q.; Xing, H. Effect of microbiota metabolites on the progression of chronic hepatitis B virus infection. Hepatol. Int. 2021, 15, 1053–1067. [Google Scholar] [CrossRef]
- Munn, D.H.; Mellor, A.L. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol. 2013, 34, 137–143. [Google Scholar] [CrossRef]
- Schmidt, S.V.; Schultze, J.L. New Insights into IDO Biology in Bacterial and Viral Infections. Front. Immunol. 2014, 5, 384. [Google Scholar] [CrossRef]
- Mao, R.; Zhang, J.; Jiang, D.; Cai, D.; Levy, J.M.; Cuconati, A.; Block, T.M.; Guo, J.T.; Guo, H. Indoleamine 2,3-dioxygenase mediates the antiviral effect of gamma interferon against hepatitis B virus in human hepatocyte-derived cells. J. Virol. 2011, 85, 1048–1057. [Google Scholar] [CrossRef]
- Yoshio, S.; Sugiyama, M.; Shoji, H.; Mano, Y.; Mita, E.; Okamoto, T.; Matsuura, Y.; Okuno, A.; Takikawa, O.; Mizokami, M.; et al. Indoleamine-2,3-dioxygenase as an effector and an indicator of protective immune responses in patients with acute hepatitis B. Hepatology 2016, 63, 83–94. [Google Scholar] [CrossRef] [PubMed]
- Shen, Y.; Wu, S.D.; Chen, Y.; Li, X.Y.; Zhu, Q.; Nakayama, K.; Zhang, W.Q.; Weng, C.Z.; Zhang, J.; Wang, H.K.; et al. Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response. Gut Microbes 2023, 15, 2155018. [Google Scholar] [CrossRef]
- Li, J.; Qiu, S.J.; She, W.M.; Wang, F.P.; Gao, H.; Li, L.; Tu, C.T.; Wang, J.Y.; Shen, X.Z.; Jiang, W. Significance of the balance between regulatory T (Treg) and T helper 17 (Th17) cells during hepatitis B virus related liver fibrosis. PLoS ONE 2012, 7, e39307. [Google Scholar] [CrossRef] [PubMed]
- Meng, F.; Wang, K.; Aoyama, T.; Grivennikov, S.I.; Paik, Y.; Scholten, D.; Cong, M.; Iwaisako, K.; Liu, X.; Zhang, M.; et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology 2012, 143, 765–776.e3. [Google Scholar] [CrossRef]
- Tan, Z.; Qian, X.; Jiang, R.; Liu, Q.; Wang, Y.; Chen, C.; Wang, X.; Ryffel, B.; Sun, B. IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation. J. Immunol. 2013, 191, 1835–1844. [Google Scholar] [CrossRef]
- Fabre, T.; Kared, H.; Friedman, S.L.; Shoukry, N.H. IL-17A enhances the expression of profibrotic genes through upregulation of the TGF-β receptor on hepatic stellate cells in a JNK-dependent manner. J. Immunol. 2014, 193, 3925–3933. [Google Scholar] [CrossRef]
- Paratore, M.; Santopaolo, F.; Cammarota, G.; Pompili, M.; Gasbarrini, A.; Ponziani, F.R. Fecal Microbiota Transplantation in Patients with HBV Infection or Other Chronic Liver Diseases: Update on Current Knowledge and Future Perspectives. J. Clin. Med. 2021, 10, 2605. [Google Scholar] [CrossRef]
- Sehgal, R.; Bedi, O.; Trehanpati, N. Role of Microbiota in Pathogenesis and Management of Viral Hepatitis. Front. Cell Infect. Microbiol. 2020, 10, 341. [Google Scholar] [CrossRef]
- Wang, J.; Zhou, X.; Li, X.; Guo, W.; Zhu, Q.; Zhu, B.; Lu, Y.; Zheng, X.; Yang, D.; Wang, B. Fecal Microbiota Transplantation Alters the Outcome of Hepatitis B Virus Infection in Mice. Front. Cell Infect. Microbiol. 2022, 12, 844132. [Google Scholar] [CrossRef]
- Ren, Y.D.; Ye, Z.S.; Yang, L.Z.; Jin, L.X.; Wei, W.J.; Deng, Y.Y.; Chen, X.X.; Xiao, C.X.; Yu, X.F.; Xu, H.Z.; et al. Fecal microbiota transplantation induces hepatitis B virus e-antigen (HBeAg) clearance in patients with positive HBeAg after long-term antiviral therapy. Hepatology 2017, 65, 1765–1768. [Google Scholar] [CrossRef]
- Chauhan, A.; Kumar, R.; Sharma, S.; Mahanta, M.; Vayuuru, S.K.; Nayak, B.; Kumar, S.; Shalimar. Fecal Microbiota Transplantation in Hepatitis B e Antigen-Positive Chronic Hepatitis B Patients: A Pilot Study. Dig. Dis. Sci. 2021, 66, 873–880. [Google Scholar] [CrossRef]
- Mukherjee, A.; Lordan, C.; Ross, R.P.; Cotter, P.D. Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health. Gut Microbes 2020, 12, 1802866. [Google Scholar] [CrossRef]
- Xia, X.; Chen, J.; Xia, J.; Wang, B.; Liu, H.; Yang, L.; Wang, Y.; Ling, Z. Role of probiotics in the treatment of minimal hepatic encephalopathy in patients with HBV-induced liver cirrhosis. J. Int. Med. Res. 2018, 46, 3596–3604. [Google Scholar] [CrossRef]
- Lu, H.; Zhu, X.; Wu, L.; Lou, X.; Pan, X.; Liu, B.; Zhang, H.; Zhu, L.; Li, L.; Wu, Z. Alterations in the intestinal microbiome and metabolic profile of patients with cirrhosis supplemented with lactulose, Clostridium butyricum, and Bifidobacterium longum infantis: A randomized placebo-controlled trial. Front. Microbiol. 2023, 14, 1169811. [Google Scholar] [CrossRef]
- Polaris Observatory HCV Collaborators. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: A modelling study. Lancet Gastroenterol. Hepatol. 2022, 7, 396–415. [Google Scholar] [CrossRef]
- Aly, A.M.; Adel, A.; El-Gendy, A.O.; Essam, T.M.; Aziz, R.K. Gut microbiome alterations in patients with stage 4 hepatitis C. Gut Pathog. 2016, 8, 42. [Google Scholar] [CrossRef]
- Heidrich, B.; Vital, M.; Plumeier, I.; Döscher, N.; Kahl, S.; Kirschner, J.; Ziegert, S.; Solbach, P.; Lenzen, H.; Potthoff, A.; et al. Intestinal microbiota in patients with chronic hepatitis C with and without cirrhosis compared with healthy controls. Liver Int. 2018, 38, 50–58. [Google Scholar] [CrossRef]
- Mizutani, T.; Ishizaka, A.; Koga, M.; Tsutsumi, T.; Yotsuyanagi, H. Role of Microbiota in Viral Infections and Pathological Progression. Viruses 2022, 14, 950. [Google Scholar] [CrossRef]
- Preveden, T.; Scarpellini, E.; Milić, N.; Luzza, F.; Abenavoli, L. Gut microbiota changes and chronic hepatitis C virus infection. Expert. Rev. Gastroenterol. Hepatol. 2017, 11, 813–819. [Google Scholar] [CrossRef]
- Dolganiuc, A.; Norkina, O.; Kodys, K.; Catalano, D.; Bakis, G.; Marshall, C.; Mandrekar, P.; Szabo, G. Viral and host factors induce macrophage activation and loss of toll-like receptor tolerance in chronic HCV infection. Gastroenterology 2007, 133, 1627–1636. [Google Scholar] [CrossRef]
- Inoue, T.; Funatsu, Y.; Ohnishi, M.; Isogawa, M.; Kawashima, K.; Tanaka, M.; Moriya, K.; Kawaratani, H.; Momoda, R.; Iio, E.; et al. Bile acid dysmetabolism in the gut-microbiota-liver axis under hepatitis C virus infection. Liver Int. 2022, 42, 124–134. [Google Scholar] [CrossRef]
- Ponziani, F.R.; Putignani, L.; Paroni Sterbini, F.; Petito, V.; Picca, A.; Del Chierico, F.; Reddel, S.; Calvani, R.; Marzetti, E.; Sanguinetti, M.; et al. Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis. Aliment. Pharmacol. Ther. 2018, 48, 1301–1311. [Google Scholar] [CrossRef] [PubMed]
- Iwata, R.; Stieger, B.; Mertens, J.C.; Müller, T.; Baur, K.; Frei, P.; Braun, J.; Vergopoulos, A.; Martin, I.V.; Schmitt, J.; et al. The role of bile acid retention and a common polymorphism in the ABCB11 gene as host factors affecting antiviral treatment response in chronic hepatitis C. J. Viral Hepat. 2011, 18, 768–778. [Google Scholar] [CrossRef]
- Inoue, T.; Nakayama, J.; Moriya, K.; Kawaratani, H.; Momoda, R.; Ito, K.; Iio, E.; Nojiri, S.; Fujiwara, K.; Yoneda, M.; et al. Gut Dysbiosis Associated With Hepatitis C Virus Infection. Clin. Infect. Dis. 2018, 67, 869–877. [Google Scholar] [CrossRef] [PubMed]
- Atarashi, K.; Tanoue, T.; Shima, T.; Imaoka, A.; Kuwahara, T.; Momose, Y.; Cheng, G.; Yamasaki, S.; Saito, T.; Ohba, Y.; et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011, 331, 337–341. [Google Scholar] [CrossRef] [PubMed]
- Furusawa, Y.; Obata, Y.; Fukuda, S.; Endo, T.A.; Nakato, G.; Takahashi, D.; Nakanishi, Y.; Uetake, C.; Kato, K.; Kato, T.; et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013, 504, 446–450. [Google Scholar] [CrossRef]
- Ullah, N.; Kakakhel, M.A.; Khan, I.; Gul Hilal, M.; Lajia, Z.; Bai, Y.; Sajjad, W.; Yuxi, L.; Ullah, H.; Almohaimeed, H.M.; et al. Structural and compositional segregation of the gut microbiota in HCV and liver cirrhotic patients: A clinical pilot study. Microb. Pathog. 2022, 171, 105739. [Google Scholar] [CrossRef] [PubMed]
- Ashour, Z.; Shahin, R.; Ali-Eldin, Z.; El-Shayeb, M.; El-Tayeb, T.; Bakr, S. Potential impact of gut Lactobacillus acidophilus and Bifidobacterium bifidum on hepatic histopathological changes in non-cirrhotic hepatitis C virus patients with different viral load. Gut Pathog. 2022, 14, 25. [Google Scholar] [CrossRef]
- Moon, M.S.; Quinn, G.; Townsend, E.C.; Ali, R.O.; Zhang, G.Y.; Bradshaw, A.; Hill, K.; Guan, H.; Hamilton, D.; Kleiner, D.E.; et al. Bacterial Translocation and Host Immune Activation in Chronic Hepatitis C Infection. Open Forum Infect. Dis. 2019, 6, ofz255. [Google Scholar] [CrossRef]
- Sultan, S.; El-Mowafy, M.; Elgaml, A.; El-Mesery, M.; El Shabrawi, A.; Elegezy, M.; Hammami, R.; Mottawea, W. Alterations of the Treatment-Naive Gut Microbiome in Newly Diagnosed Hepatitis C Virus Infection. ACS Infect. Dis. 2021, 7, 1059–1068. [Google Scholar] [CrossRef]
- Wellhöner, F.; Döscher, N.; Tergast, T.L.; Vital, M.; Plumeier, I.; Kahl, S.; Potthoff, A.; Manns, M.P.; Maasoumy, B.; Wedemeyer, H.; et al. The impact of proton pump inhibitors on the intestinal microbiota in chronic hepatitis C patients. Scand. J. Gastroenterol. 2019, 54, 1033–1041. [Google Scholar] [CrossRef]
- El-Mowafy, M.; Elgaml, A.; El-Mesery, M.; Sultan, S.; Ahmed, T.A.E.; Gomaa, A.I.; Aly, M.; Mottawea, W. Changes of Gut-Microbiota-Liver Axis in Hepatitis C Virus Infection. Biology 2021, 10, 55. [Google Scholar] [CrossRef]
- Neag, M.A.; Mitre, A.O.; Catinean, A.; Buzoianu, A.D. Overview of the microbiota in the gut-liver axis in viral B and C hepatitis. World J. Gastroenterol. 2021, 27, 7446–7461. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Sterling, R.K.; Betrapally, N.S.; Nixon, D.E.; Fuchs, M.; Daita, K.; Heuman, D.M.; Sikaroodi, M.; Hylemon, P.B.; White, M.B.; et al. HCV eradication does not impact gut dysbiosis or systemic inflammation in cirrhotic patients. Aliment. Pharmacol. Ther. 2016, 44, 638–643. [Google Scholar] [CrossRef]
- Pérez-Matute, P.; Íñiguez, M.; Villanueva-Millán, M.J.; Recio-Fernández, E.; Vázquez, A.M.; Sánchez, S.C.; Morano, L.E.; Oteo, J.A. Short-term effects of direct-acting antiviral agents on inflammation and gut microbiota in hepatitis C-infected patients. Eur. J. Intern. Med. 2019, 67, 47–58. [Google Scholar] [CrossRef]
- Wellhöner, F.; Döscher, N.; Woelfl, F.; Vital, M.; Plumeier, I.; Kahl, S.; Potthoff, A.; Manns, M.P.; Pieper, D.H.; Cornberg, M.; et al. Eradication of Chronic HCV Infection: Improvement of Dysbiosis Only in Patients Without Liver Cirrhosis. Hepatology 2021, 74, 72–82. [Google Scholar] [CrossRef]
- Yilmaz, B.; Ruckstuhl, L.; Müllhaupt, B.; Magenta, L.; Kuster, M.H.; Clerc, O.; Torgler, R.; Semmo, N. Pilot Sub-Study of the Effect of Hepatitis C Cure by Glecaprevir/Pibrentasvir on the Gut Microbiome of Patients with Chronic Hepatitis C Genotypes 1 to 6 in the Mythen Study. Pharmaceuticals 2021, 14, 931. [Google Scholar] [CrossRef]
- Huang, P.Y.; Chen, C.H.; Tsai, M.J.; Yao, C.C.; Wang, H.M.; Kuo, Y.H.; Chang, K.C.; Hung, C.H.; Chuah, S.K.; Tsai, M.C. Effects of direct anti-viral agents on the gut microbiota in patients with chronic hepatitis C. J. Formos. Med. Assoc. 2023, 122, 157–163. [Google Scholar] [CrossRef]
- Hsu, Y.C.; Chen, C.C.; Lee, W.H.; Chang, C.Y.; Lee, F.J.; Tseng, C.H.; Chen, T.H.; Ho, H.J.; Lin, J.T.; Wu, C.Y. Compositions of gut microbiota before and shortly after hepatitis C viral eradication by direct antiviral agents. Sci. Rep. 2022, 12, 5481. [Google Scholar] [CrossRef]
- Honda, T.; Ishigami, M.; Yamamoto, K.; Takeyama, T.; Ito, T.; Ishizu, Y.; Kuzuya, T.; Nakamura, M.; Kawashima, H.; Miyahara, R.; et al. Changes in the gut microbiota after hepatitis C virus eradication. Sci. Rep. 2021, 11, 23568. [Google Scholar] [CrossRef]
- Chuaypen, N.; Jinato, T.; Avihingsanon, A.; Nookaew, I.; Tanaka, Y.; Tangkijvanich, P. Long-term benefit of DAAs on gut dysbiosis and microbial translocation in HCV-infected patients with and without HIV coinfection. Sci. Rep. 2023, 13, 14413. [Google Scholar] [CrossRef]
- Lattanzi, B.; Baroncelli, S.; De Santis, A.; Galluzzo, C.M.; Mennini, G.; Michelini, Z.; Lupo, M.; Ginanni Corradini, S.; Rossi, M.; Palmisano, L.; et al. Microbial translocation and T cell activation are modified by direct-acting antiviral therapy in HCV-infected patients. Aliment. Pharmacol. Ther. 2018, 48, 1146–1155. [Google Scholar] [CrossRef]
- Torres-Barceló, C. The disparate effects of bacteriophages on antibiotic-resistant bacteria. Emerg. Microbes Infect. 2018, 7, 168. [Google Scholar] [CrossRef] [PubMed]
- Stern, J.; Miller, G.; Li, X.; Saxena, D. Virome and bacteriome: Two sides of the same coin. Curr. Opin. Virol. 2019, 37, 37–43. [Google Scholar] [CrossRef] [PubMed]
- Wu, J.; Bortolanza, M.; Zhai, G.; Shang, A.; Ling, Z.; Jiang, B.; Shen, X.; Yao, Y.; Yu, J.; Li, L.; et al. Gut microbiota dysbiosis associated with plasma levels of Interferon-γ and viral load in patients with acute hepatitis E infection. J. Med. Virol. 2022, 94, 692–702. [Google Scholar] [CrossRef] [PubMed]
- Wu, J.; Huang, F.; Ling, Z.; Liu, S.; Liu, J.; Fan, J.; Yu, J.; Wang, W.; Jin, X.; Meng, Y.; et al. Altered faecal microbiota on the expression of Th cells responses in the exacerbation of patients with hepatitis E infection. J. Viral Hepat. 2020, 27, 1243–1252. [Google Scholar] [CrossRef] [PubMed]
- Kreuzer, S.; Machnowska, P.; Aßmus, J.; Sieber, M.; Pieper, R.; Schmidt, M.F.; Brockmann, G.A.; Scharek-Tedin, L.; Johne, R. Feeding of the probiotic bacterium Enterococcus faecium NCIMB 10415 differentially affects shedding of enteric viruses in pigs. Vet Res. 2012, 43, 58. [Google Scholar] [CrossRef]
- Ishizaka, A.; Koga, M.; Mizutani, T.; Lim, L.A.; Adachi, E.; Ikeuchi, K.; Ueda, R.; Aoyagi, H.; Tanaka, S.; Kiyono, H.; et al. Prolonged Gut Dysbiosis and Fecal Excretion of Hepatitis A Virus in Patients Infected with Human Immunodeficiency Virus. Viruses. 2021, 13, 2101. [Google Scholar] [CrossRef]
- Kefalakes, H.; Rehermann, B. Inflammation drives an altered phenotype of mucosal-associated invariant T cells in chronic hepatitis D virus infection. J. Hepatol. 2019, 71, 237–239. [Google Scholar] [CrossRef]
- Bhat, M.; Arendt, B.M.; Bhat, V.; Renner, E.L.; Humar, A.; Allard, J.P. Implication of the intestinal microbiome in complications of cirrhosis. World J. Hepatol. 2016, 8, 1128–1136. [Google Scholar] [CrossRef]
- Kakiyama, G.; Pandak, W.M.; Gillevet, P.M.; Hylemon, P.B.; Heuman, D.M.; Daita, K.; Takei, H.; Muto, A.; Nittono, H.; Ridlon, J.M.; et al. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. J. Hepatol. 2013, 58, 949–955. [Google Scholar] [CrossRef]
- Chen, Y.; Ji, F.; Guo, J.; Shi, D.; Fang, D.; Li, L. Dysbiosis of small intestinal microbiota in liver cirrhosis and its association with etiology. Sci. Rep. 2016, 6, 34055. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Heuman, D.M.; Hylemon, P.B.; Sanyal, A.J.; White, M.B.; Monteith, P.; Noble, N.A.; Unser, A.B.; Daita, K.; Fisher, A.R.; et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J. Hepatol. 2014, 60, 940–947. [Google Scholar] [CrossRef]
- Assimakopoulos, S.F.; Tsamandas, A.C.; Tsiaoussis, G.I.; Karatza, E.; Triantos, C.; Vagianos, C.E.; Spiliopoulou, I.; Kaltezioti, V.; Charonis, A.; Nikolopoulou, V.N.; et al. Altered intestinal tight junctions’ expression in patients with liver cirrhosis: A pathogenetic mechanism of intestinal hyperpermeability. Eur. J. Clin. Investig. 2012, 42, 439–446. [Google Scholar] [CrossRef]
- Teltschik, Z.; Wiest, R.; Beisner, J.; Nuding, S.; Hofmann, C.; Schoelmerich, J.; Bevins, C.L.; Stange, E.F.; Wehkamp, J. Intestinal bacterial translocation in rats with cirrhosis is related to compromised Paneth cell antimicrobial host defense. Hepatology 2012, 55, 1154–1163. [Google Scholar] [CrossRef]
- Simbrunner, B.; Trauner, M.; Reiberger, T. Review article: Therapeutic aspects of bile acid signalling in the gut-liver axis. Aliment. Pharmacol. Ther. 2021, 54, 1243–1262. [Google Scholar] [CrossRef]
- Shao, J.W.; Ge, T.T.; Chen, S.Z.; Wang, G.; Yang, Q.; Huang, C.H.; Xu, L.C.; Chen, Z. Role of bile acids in liver diseases mediated by the gut microbiome. World J. Gastroenterol. 2021, 27, 3010–3021. [Google Scholar] [CrossRef]
- Sauerbruch, T.; Hennenberg, M.; Trebicka, J.; Beuers, U. Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction. Front. Physiol. 2021, 12, 718783. [Google Scholar] [CrossRef]
- Liu, Y.; Chen, K.; Li, F.; Gu, Z.; Liu, Q.; He, L.; Shao, T.; Song, Q.; Zhu, F.; Zhang, L.; et al. Probiotic Lactobacillus rhamnosus GG Prevents Liver Fibrosis Through Inhibiting Hepatic Bile Acid Synthesis and Enhancing Bile Acid Excretion in Mice. Hepatology 2020, 71, 2050–2066. [Google Scholar] [CrossRef]
- Albillos, A.; Martin-Mateos, R.; Van der Merwe, S.; Wiest, R.; Jalan, R.; Álvarez-Mon, M. Cirrhosis-associated immune dysfunction. Nat. Rev. Gastroenterol. Hepatol. 2022, 19, 112–134. [Google Scholar] [CrossRef]
- Kaliannan, K. Compromise of α-Defensin Function in Liver Cirrhosis Facilitates the Toxic Relationship Between Gut Permeability and Endotoxemia. Dig. Dis. Sci. 2018, 63, 2492–2494. [Google Scholar] [CrossRef]
- Hassan, M.; Moghadamrad, S.; Sorribas, M.; Muntet, S.G.; Kellmann, P.; Trentesaux, C.; Fraudeau, M.; Nanni, P.; Wolski, W.; Keller, I.; et al. Paneth cells promote angiogenesis and regulate portal hypertension in response to microbial signals. J. Hepatol. 2020, 73, 628–639. [Google Scholar] [CrossRef]
- Hrncir, T.; Hrncirova, L.; Kverka, M.; Hromadka, R.; Machova, V.; Trckova, E.; Kostovcikova, K.; Kralickova, P.; Krejsek, J.; Tlaskalova-Hogenova, H. Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions. Microorganisms 2021, 9, 957. [Google Scholar] [CrossRef]
- Kassa, Y.; Million, Y.; Gedefie, A.; Moges, F. Alteration of Gut Microbiota and Its Impact on Immune Response in Patients with Chronic HBV Infection: A Review. Infect. Drug Resist. 2021, 14, 2571–2578. [Google Scholar] [CrossRef]
- Kisseleva, T.; Brenner, D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat. Rev. Gastroenterol. Hepatol. 2021, 18, 151–166. [Google Scholar] [CrossRef]
- Parola, M.; Pinzani, M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. Mol. Aspects Med. 2019, 65, 37–55. [Google Scholar] [CrossRef]
- Strowig, T.; Henao-Mejia, J.; Elinav, E.; Flavell, R. Inflammasomes in health and disease. Nature 2012, 481, 278–286. [Google Scholar] [CrossRef]
- Schroder, K.; Tschopp, J. The inflammasomes. Cell 2010, 140, 821–832. [Google Scholar] [CrossRef]
- Watanabe, A.; Sohail, M.A.; Gomes, D.A.; Hashmi, A.; Nagata, J.; Sutterwala, F.S.; Mahmood, S.; Jhandier, M.N.; Shi, Y.; Flavell, R.A.; et al. Inflammasome-mediated regulation of hepatic stellate cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 296, G1248–G1257. [Google Scholar] [CrossRef]
- Boaru, S.G.; Borkham-Kamphorst, E.; Tihaa, L.; Haas, U.; Weiskirchen, R. Expression analysis of inflammasomes in experimental models of inflammatory and fibrotic liver disease. J. Inflamm. 2012, 9, 49. [Google Scholar] [CrossRef]
- Gurung, P.; Li, B.; Subbarao Malireddi, R.K.; Lamkanfi, M.; Geiger, T.L.; Kanneganti, T.D. Chronic TLR Stimulation Controls NLRP3 Inflammasome Activation through IL-10 Mediated Regulation of NLRP3 Expression and Caspase-8 Activation. Sci. Rep. 2015, 5, 14488. [Google Scholar] [CrossRef]
- Chuang, S.Y.; Yang, C.H.; Chou, C.C.; Chiang, Y.P.; Chuang, T.H.; Hsu, L.C. TLR-induced PAI-2 expression suppresses IL-1β processing via increasing autophagy and NLRP3 degradation. Proc. Natl. Acad. Sci. USA 2013, 110, 16079–16084. [Google Scholar] [CrossRef]
- Arab, J.P.; Martin-Mateos, R.M.; Shah, V.H. Gut-liver axis, cirrhosis and portal hypertension: The chicken and the egg. Hepatol. Int. 2018, 12, 24–33. [Google Scholar] [CrossRef]
- Johnson, K.V.; Foster, K.R. Why does the microbiome affect behaviour? Nat. Rev. Microbiol. 2018, 16, 647–655. [Google Scholar] [CrossRef]
- Ding, J.H.; Jin, Z.; Yang, X.X.; Lou, J.; Shan, W.X.; Hu, Y.X.; Du, Q.; Liao, Q.S.; Xie, R.; Xu, J.Y. Role of gut microbiota via the gut-liver-brain axis in digestive diseases. World J. Gastroenterol. 2020, 26, 6141–6162. [Google Scholar] [CrossRef]
- Smith, M.L.; Wade, J.B.; Wolstenholme, J.; Bajaj, J.S. Gut microbiome-brain-cirrhosis axis. Hepatology 2023. [Google Scholar] [CrossRef]
- Won, S.M.; Oh, K.K.; Gupta, H.; Ganesan, R.; Sharma, S.P.; Jeong, J.J.; Yoon, S.J.; Jeong, M.K.; Min, B.H.; Hyun, J.Y.; et al. The Link between Gut Microbiota and Hepatic Encephalopathy. Int. J. Mol. Sci. 2022, 23, 8999. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Hylemon, P.B.; Ridlon, J.M.; Heuman, D.M.; Daita, K.; White, M.B.; Monteith, P.; Noble, N.A.; Sikaroodi, M.; Gillevet, P.M. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 303, G675–G685. [Google Scholar] [CrossRef]
- Zhu, R.; Liu, L.; Zhang, G.; Dong, J.; Ren, Z.; Li, Z. The pathogenesis of gut microbiota in hepatic encephalopathy by the gut-liver-brain axis. Biosci. Rep. 2023, 43, BSR20222524. [Google Scholar] [CrossRef]
- Xie, G.; Wang, X.; Jiang, R.; Zhao, A.; Yan, J.; Zheng, X.; Huang, F.; Liu, X.; Panee, J.; Rajani, C.; et al. Dysregulated bile acid signaling contributes to the neurological impairment in murine models of acute and chronic liver failure. EBioMedicine 2018, 37, 294–306. [Google Scholar] [CrossRef]
- Ridlon, J.M.; Alves, J.M.; Hylemon, P.B.; Bajaj, J.S. Cirrhosis, bile acids and gut microbiota: Unraveling a complex relationship. Gut Microbes 2013, 4, 382–387. [Google Scholar] [CrossRef]
- Sung, C.M.; Lin, Y.F.; Chen, K.F.; Ke, H.M.; Huang, H.Y.; Gong, Y.N.; Tsai, W.S.; You, J.F.; Lu, M.J.; Cheng, H.T.; et al. Predicting Clinical Outcomes of Cirrhosis Patients With Hepatic Encephalopathy From the Fecal Microbiome. Cell Mol. Gastroenterol. Hepatol. 2019, 8, 301–318.e2. [Google Scholar] [CrossRef]
- Zhang, Z.; Zhai, H.; Geng, J.; Yu, R.; Ren, H.; Fan, H.; Shi, P. Large-scale survey of gut microbiota associated with MHE Via 16S rRNA-based pyrosequencing. Am. J. Gastroenterol. 2013, 108, 1601–1611. [Google Scholar] [CrossRef]
- Luo, M.; Hu, F.R.; Xin, R.J.; Yao, L.; Hu, S.J.; Bai, F.H. Altered gut microbiota is associated with sleep disturbances in patients with minimal hepatic encephalopathy caused by hepatitis B-related liver cirrhosis. Expert. Rev. Gastroenterol. Hepatol. 2022, 16, 797–807. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Ridlon, J.M.; Hylemon, P.B.; Thacker, L.R.; Heuman, D.M.; Smith, S.; Sikaroodi, M.; Gillevet, P.M. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 302, G168–G175. [Google Scholar] [CrossRef]
- Ahluwalia, V.; Betrapally, N.S.; Hylemon, P.B.; White, M.B.; Gillevet, P.M.; Unser, A.B.; Fagan, A.; Daita, K.; Heuman, D.M.; Zhou, H.; et al. Impaired Gut-Liver-Brain Axis in Patients with Cirrhosis. Sci. Rep. 2016, 6, 26800. [Google Scholar] [CrossRef]
- Yukawa-Muto, Y.; Kamiya, T.; Fujii, H.; Mori, H.; Toyoda, A.; Sato, I.; Konishi, Y.; Hirayama, A.; Hara, E.; Fukuda, S.; et al. Distinct responsiveness to rifaximin in patients with hepatic encephalopathy depends on functional gut microbial species. Hepatol. Commun. 2022, 6, 2090–2104. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Shamsaddini, A.; Fagan, A.; McGeorge, S.; Gavis, E.; Sikaroodi, M.; Brenner, L.A.; Wade, J.B.; Gillevet, P.M. Distinct gut microbial compositional and functional changes associated with impaired inhibitory control in patients with cirrhosis. Gut Microbes 2021, 13, 1953247. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Fagan, A.; White, M.B.; Wade, J.B.; Hylemon, P.B.; Heuman, D.M.; Fuchs, M.; John, B.V.; Acharya, C.; Sikaroodi, M.; et al. Specific Gut and Salivary Microbiota Patterns Are Linked With Different Cognitive Testing Strategies in Minimal Hepatic Encephalopathy. Am. J. Gastroenterol. 2019, 114, 1080–1090. [Google Scholar] [CrossRef]
- Luo, M.; Xin, R.J.; Hu, F.R.; Yao, L.; Hu, S.J.; Bai, F.H. Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis. World J. Gastroenterol. 2023, 29, 144–156. [Google Scholar] [CrossRef]
- Alberts, C.J.; Clifford, G.M.; Georges, D.; Negro, F.; Lesi, O.A.; Hutin, Y.J.; de Martel, C. Worldwide prevalence of hepatitis B virus and hepatitis C virus among patients with cirrhosis at country, region, and global levels: A systematic review. Lancet Gastroenterol. Hepatol. 2022, 7, 724–735. [Google Scholar] [CrossRef]
- Li, Y.G.; Yu, Z.J.; Li, A.; Ren, Z.G. Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions. World J. Gastroenterol. 2022, 28, 3555–3572. [Google Scholar] [CrossRef]
- Xu, M.; Luo, K.; Li, J.; Li, Y.; Zhang, Y.; Yuan, Z.; Xu, Q.; Wu, X. Role of Intestinal Microbes in Chronic Liver Diseases. Int. J. Mol. Sci. 2022, 23, 12661. [Google Scholar] [CrossRef]
- Wu, Z.W.; Lu, H.F.; Wu, J.; Zuo, J.; Chen, P.; Sheng, J.F.; Zheng, S.S.; Li, L.J. Assessment of the fecal lactobacilli population in patients with hepatitis B virus-related decompensated cirrhosis and hepatitis B cirrhosis treated with liver transplant. Microb. Ecol. 2012, 63, 929–937. [Google Scholar] [CrossRef]
- Deng, Y.D.; Peng, X.B.; Zhao, R.R.; Ma, C.Q.; Li, J.N.; Yao, L.Q. The intestinal microbial community dissimilarity in hepatitis B virus-related liver cirrhosis patients with and without at alcohol consumption. Gut Pathog. 2019, 11, 58. [Google Scholar] [CrossRef]
- Cani, P.D.; Jordan, B.F. Gut microbiota-mediated inflammation in obesity: A link with gastrointestinal cancer. Nat. Rev. Gastroenterol. Hepatol. 2018, 15, 671–682. [Google Scholar] [CrossRef]
- Kajihara, M.; Koido, S.; Kanai, T.; Ito, Z.; Matsumoto, Y.; Takakura, K.; Saruta, M.; Kato, K.; Odamaki, T.; Xiao, J.Z.; et al. Characterisation of blood microbiota in patients with liver cirrhosis. Eur. J. Gastroenterol. Hepatol. 2019, 31, 1577–1583. [Google Scholar] [CrossRef]
- Zheng, R.; Wang, G.; Pang, Z.; Ran, N.; Gu, Y.; Guan, X.; Yuan, Y.; Zuo, X.; Pan, H.; Zheng, J.; et al. Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma. Cancer Med. 2020, 9, 4232–4250. [Google Scholar] [CrossRef]
- Sun, X.; Chi, X.; Zhao, Y.; Liu, S.; Xing, H. Characteristics and Clinical Significance of Intestinal Microbiota in Patients with Chronic Hepatitis B Cirrhosis and Type 2 Diabetes Mellitus. J. Diabetes Res. 2022, 2022, 1826181. [Google Scholar] [CrossRef]
- Fasano, A.; Not, T.; Wang, W.; Uzzau, S.; Berti, I.; Tommasini, A.; Goldblum, S.E. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 2000, 355, 1518–1519. [Google Scholar] [CrossRef]
- Jiang, J.W.; Chen, X.H.; Ren, Z.; Zheng, S.S. Gut microbial dysbiosis associates hepatocellular carcinoma via the gut-liver axis. Hepatobiliary Pancreat. Dis. Int. 2019, 18, 19–27. [Google Scholar] [CrossRef]
- Behary, J.; Amorim, N.; Jiang, X.T.; Raposo, A.; Gong, L.; McGovern, E.; Ibrahim, R.; Chu, F.; Stephens, C.; Jebeili, H.; et al. Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma. Nat. Commun. 2021, 12, 187. [Google Scholar] [CrossRef]
- Ponziani, F.R.; Bhoori, S.; Castelli, C.; Putignani, L.; Rivoltini, L.; Del Chierico, F.; Sanguinetti, M.; Morelli, D.; Paroni Sterbini, F.; Petito, V.; et al. Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease. Hepatology 2019, 69, 107–120. [Google Scholar] [CrossRef]
- Khalyfa, A.A.; Punatar, S.; Yarbrough, A. Hepatocellular Carcinoma: Understanding the Inflammatory Implications of the Microbiome. Int. J. Mol. Sci. 2022, 23, 8164. [Google Scholar] [CrossRef]
- Rajapakse, J.; Khatiwada, S.; Akon, A.C.; Yu, K.L.; Shen, S.; Zekry, A. Unveiling the complex relationship between gut microbiota and liver cancer: Opportunities for novel therapeutic interventions. Gut Microbes 2023, 15, 2240031. [Google Scholar] [CrossRef]
- Liu, S.; Yang, X. Intestinal flora plays a role in the progression of hepatitis-cirrhosis-liver cancer. Front. Cell Infect. Microbiol. 2023, 13, 1140126. [Google Scholar] [CrossRef]
- Mohamadkhani, A. On the potential role of intestinal microbial community in hepatocarcinogenesis in chronic hepatitis B. Cancer Med. 2018, 7, 3095–3100. [Google Scholar] [CrossRef]
- Wu, L.; Feng, J.; Li, J.; Yu, Q.; Ji, J.; Wu, J.; Dai, W.; Guo, C. The gut microbiome-bile acid axis in hepatocarcinogenesis. Biomed. Pharmacother. 2021, 133, 111036. [Google Scholar] [CrossRef]
- Marascio, N.; De Caro, C.; Quirino, A.; Mazzitelli, M.; Russo, E.; Torti, C.; Matera, G. The Role of the Microbiota Gut-Liver Axis during HCV Chronic Infection: A Schematic Overview. J. Clin. Med. 2022, 11, 5936. [Google Scholar] [CrossRef]
- Virseda-Berdices, A.; Brochado-Kith, O.; Díez, C.; Hontañon, V.; Berenguer, J.; González-García, J.; Rojo, D.; Fernández-Rodríguez, A.; Ibañez-Samaniego, L.; Llop-Herrera, E.; et al. Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis. J. Antimicrob. Chemother. 2022, 77, 719–726. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Salzman, N.H.; Acharya, C.; Sterling, R.K.; White, M.B.; Gavis, E.A.; Fagan, A.; Hayward, M.; Holtz, M.L.; Matherly, S.; et al. Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial. Hepatology 2019, 70, 1690–1703. [Google Scholar] [CrossRef]
- Bloom, P.P.; Donlan, J.; Torres Soto, M.; Daidone, M.; Hohmann, E.; Chung, R.T. Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient. Hepatol. Commun. 2022, 6, 2079–2089. [Google Scholar] [CrossRef]
- Sarangi, A.N.; Goel, A.; Singh, A.; Sasi, A.; Aggarwal, R. Faecal bacterial microbiota in patients with cirrhosis and the effect of lactulose administration. BMC Gastroenterol. 2017, 17, 125. [Google Scholar] [CrossRef] [PubMed]
- Moratalla, A.; Ampuero, J.; Bellot, P.; Gallego-Durán, R.; Zapater, P.; Roger, M.; Figueruela, B.; Martínez-Moreno, B.; González-Navajas, J.M.; Such, J.; et al. Lactulose reduces bacterial DNA translocation, which worsens neurocognitive shape in cirrhotic patients with minimal hepatic encephalopathy. Liver Int. 2017, 37, 212–223. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.Y.; Bajaj, J.S.; Wang, J.B.; Shang, J.; Zhou, X.M.; Guo, X.L.; Zhu, X.; Meng, L.N.; Jiang, H.X.; Mi, Y.Q.; et al. Lactulose improves cognition, quality of life, and gut microbiota in minimal hepatic encephalopathy: A multicenter, randomized controlled trial. J. Dig. Dis. 2019, 20, 547–556. [Google Scholar] [CrossRef] [PubMed]
- Bajaj, J.S.; Heuman, D.M.; Sanyal, A.J.; Hylemon, P.B.; Sterling, R.K.; Stravitz, R.T.; Fuchs, M.; Ridlon, J.M.; Daita, K.; Monteith, P.; et al. Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy. PLoS ONE 2013, 8, e60042. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Heuman, D.M.; Hylemon, P.B.; Sanyal, A.J.; Puri, P.; Sterling, R.K.; Luketic, V.; Stravitz, R.T.; Siddiqui, M.S.; Fuchs, M.; et al. Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Aliment. Pharmacol. Ther. 2014, 39, 1113–1125. [Google Scholar] [CrossRef]
- Manzhalii, E.; Moyseyenko, V.; Kondratiuk, V.; Molochek, N.; Falalyeyeva, T.; Kobyliak, N. Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment. World J. Hepatol. 2022, 14, 634–646. [Google Scholar] [CrossRef]
- Zuo, Z.; Fan, H.; Tang, X.D.; Chen, Y.M.; Xun, L.T.; Li, Y.; Song, Z.J.; Zhai, H.Q. Effect of different treatments and alcohol addiction on gut microbiota in minimal hepatic encephalopathy patients. Exp. Ther. Med. 2017, 14, 4887–4895. [Google Scholar] [CrossRef]
- Liu, Q.; Duan, Z.P.; Ha, D.K.; Bengmark, S.; Kurtovic, J.; Riordan, S.M. Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 2004, 39, 1441–1449. [Google Scholar] [CrossRef]
- Bajaj, J.S.; Kassam, Z.; Fagan, A.; Gavis, E.A.; Liu, E.; Cox, I.J.; Kheradman, R.; Heuman, D.; Wang, J.; Gurry, T.; et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology 2017, 66, 1727–1738. [Google Scholar] [CrossRef]
Healthy Individuals Phyla | Genera | Chronic HBV | Chronic HCV | Cirrhosis | Hepatic Encephalopathy | HCC |
---|---|---|---|---|---|---|
Proteobacteria | Escherichia Klebsiella | |||||
Firmicutes | Clostridia Blautia Enterococcus Ruminococcus Lactobacilli Streptococci | |||||
Actinobacteria | Bifidobacteria Collinsella | |||||
Bacteroidetes | Bacteroides Prevotella | |||||
Verrucomicrob | Akkermansia |
Treatment | HBV Cirrhosis | HCV Cirrhosis | Hepatic Encephalopathy | Reference |
---|---|---|---|---|
Lactulose | Improvement but all phyla increased in non-responders | No change | Bifidibacteria ↑ Bact. Translocation ↓ | [322,323,324] |
Rifaximin | Improvement Eurobacteriaceae ↑ Veillonellaceae ↓ | [325] | ||
Probiotics | Diversity,dysbiosis ↓ No cange in cognition Enterobacteriaceae ↓ Clostridiales ↑ Clostridia ↑ Bifidobacteria ↑ Firmicutes ↓ Streptoccoceae ↓ Clostridia ↓ Lactobacilli ↑ | [221,326,327,328] | ||
Synbiotics | Improvement Lactobacilli ↑ | [329] | ||
Fecal Transplant | Dysbiosis ↓ Diversity ↑ Ruminobacteria ↑ Bifidobacteria ↑ Streptococcus ↓ Veillonella ↓ HBeAg clearance ↑ | Impoved cognition Bifidobacteria ↑ | [218,219,321,328] | |
Entecavir | E.Hallii ↑ Blautia ↑ Ruminococcus ↑ Akkermansia ↑ | [167,210] | ||
DAAs | Enterobacteriaceae ↓ Staphylococcus ↓ Dysbiosis ↓ Diversity increased only after reduction of Portal Hypertension No change Dysbiosis ↓ Collinsella Bifidobacterium Only in non-cirrhotics No difference before and after SVR No change in diversity Faecalibacterium ↑ Bacillus ↑ | [230,242,244,245,247,248,319] |
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Kouroumalis, E.; Tsomidis, I.; Voumvouraki, A. Viral Liver Disease and Intestinal Gut–Liver Axis. Gastrointest. Disord. 2024, 6, 64-93. https://doi.org/10.3390/gidisord6010005
Kouroumalis E, Tsomidis I, Voumvouraki A. Viral Liver Disease and Intestinal Gut–Liver Axis. Gastrointestinal Disorders. 2024; 6(1):64-93. https://doi.org/10.3390/gidisord6010005
Chicago/Turabian StyleKouroumalis, Elias, Ioannis Tsomidis, and Argyro Voumvouraki. 2024. "Viral Liver Disease and Intestinal Gut–Liver Axis" Gastrointestinal Disorders 6, no. 1: 64-93. https://doi.org/10.3390/gidisord6010005