Targeting Microbiota and Liver Diseases: from Basic Prospective to Recent Advance Treatments-Scilight

Trends in Immunotherapy

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Targeting Microbiota and Liver Diseases: from Basic Prospective to Recent Advance Treatments

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Timur, P., Hatem , M. S., Jasim, I. K., Albasri, R. J. K., Waleed, K., & Nurlanovna, O. A. (2025). Targeting Microbiota and Liver Diseases: from Basic Prospective to Recent Advance Treatments. Trends in Immunotherapy, 9(3), 164–182. https://doi.org/10.54963/ti.v9i3.1023

Authors

  • Paizildaev Timur

    Medical Faculty, Osh State University, Osh 723500, Kyrgyzstan
  • Mortada Saleh Hatem

    Department of Medical Laboratory Analysis, Al Mansour University College, Baghdad 10067, Iraq
  • Ihsan Khudhair Jasim

    Department of Medical Laboratory Analysis, Al‑Turath University, Baghdad 10013, Iraq
  • Ridha Jawad Kadhim Albasri

    Department of Medical Laboratory Analysis, l‑Raϐidain University College, Baghdad 10064, Iraq
  • Khalid Waleed

    Department of Medical Laboratory Analysis, Madenat Alelem University College, Baghdad 10006, Iraq
  • Omorova Aizhan Nurlanovna

    Department of Clinical Disciplines , Osh State University, Osh 723500, Kyrgyzstan

Received: 14 February 2025; Revised: 18 March 2025; Accepted: 24 March 2025; Published: 22 August 2025

The diverse community of microorganisms residing in the human digestive tract, known as the intestinal microbiome, plays a crucial role in the development and progression of various liver diseases. Disruptions in the gut-liver axis have been associated with various liver conditions, including non-alcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, cirrhosis of liver, and hepatocellular carcinoma. Intestinal dysbiosis can worsen liver disease by promoting systemic inflammation, influencing immune responses, and altering metabolic pathways. This review explores the intricate connection between gut microbiome and liver diseases, highlighting fecal microbiome transplantation as a potential therapeutic approach. Considering search through databases using keywords including “liver disease” AND “microbiome” we found 62 clinical trials out of total 3,303 articles on microbiome changes to find promising treatment of liver disease. Totally 55 articles were assessed, of which most of the studies were about using probiotics, the diet and exercise, and finally FMT. NAFLD was the most predominant liver disease targeted for intervention and treatment. Most of studies (47/55: 85.45%) reported targeting microbiome as an effective and promising treatment. Probiotics and prebiotics also show promise in mitigating liver dysfunction by modulating gut microbiome and influencing adipokines, key regulators in metabolic and inflammatory processes. Despite advancements, significant gaps persist, particularly regarding FMT applications in chronic viral hepatitis and HCC. Further clinical trials are essential to optimize gut microbiome-targeted therapies for liver disease management. This review emphasizes the need for a multidisciplinary approach to bridge the gap between microbial science and therapeutic innovations in hepatology.

Keywords:

Gut Microbiome Liver Diseases NAFLD Fecal Microbiota Transplantation Modulation of Microbiome

References

  1. Zhou, X.-D.; Chen, Q.-F.; Yang, W.; et al. Burden of disease attributable to high body mass index: an analysis of data from the Global Burden of Disease Study 2021. EClinicalMedicine 2024, 76. DOI: https://doi.org/10.1016/j.eclinm.2024.102848
  2. Abdelaal, M.; le Roux, C.W.; Docherty, N.G. Morbidity and mortality associated with obesity. Ann. Transl. Med. 2017, 5, 161. DOI: https://doi.org/10.21037/atm.2017.03.107
  3. Wang, X.; You, J.; Tang, J.; et al. Interaction between non-alcoholic fatty liver disease and obesity on the risk of developing cardiovascular diseases. Sci. Rep. 2024, 14, 24024. DOI: https://doi.org/10.1038/s41598-024-74841-3
  4. Bhatt, H.B.; Smith, R.J. Fatty liver disease in diabetes mellitus. Hepatobiliary Surg. Nutr. 2015, 4, 101–108. DOI: https://doi.org/10.3978/j.issn.2304-3881.2015.01.03
  5. Pouwels, S.; Sakran, N.; Graham, Y.; et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr. Disord. 2022, 22, 63. DOI: https://doi.org/10.1186/s12902-022-00980-1
  6. Kim, C.H.; Younossi, Z.M. Nonalcoholic fatty liver disease: a manifestation of the metabolic syndrome. Cleve. Clin. J. Med. 2008, 75, 721–728. DOI: https://doi.org/10.3949/ccjm.75.10.721
  7. Golabi, P.; Paik, J.M.; Eberly, K.; et al. Causes of death in patients with Non-alcoholic Fatty Liver Disease (NAFLD), alcoholic liver disease and chronic viral Hepatitis B and C. Ann. Hepatol. 2022, 27.
  8. Chávez-Tapia, N.C.; Méndez-Sánchez, N.; Uribe, M. Role of nonalcoholic fatty liver disease in hepatocellular carcinoma. Ann. Hepatol. 2009, 8, S34–S39.
  9. Lonardo, A.; Mantovani, A.; Lugari, S.; et al. Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity. Ann. Hepatol. 2020, 19, 359–366.
  10. Jamali, R.; Hatami, N.; Kosari, F. The Correlation Between Serum Adipokines and Liver Cell Damage in Non-Alcoholic Fatty Liver Disease. Hepat. Mon. 2016, 16, e37412.
  11. Jiang, H.; Peng, Y.; Zhang, W.; et al. Gut microbiome-targeted therapies in liver cirrhosis: a protocol for systematic review and meta-analysis. Syst Rev 2022, 11, 181.
  12. Naghipour, A.; Amini-Salehi, E.; Gorabzarmakhi, O.M.; et al. Effects of gut microbial therapy on lipid profile in individuals with non-alcoholic fatty liver disease: an umbrella meta-analysis study. Syst Rev 2023, 12, 144.
  13. Sherf-Dagan, S., et al. The effect of probiotics on hepatic steatosis: A randomized, double-blind, placebo-controlled trial. Clinical Nutrition 2018, 37, 80–86..
  14. Olvera-Rosales, L.B.; Cruz-Guerrero, A.E.; Ramírez-Moreno, E.; et al. Impact of the Gut Microbiome Balance on the Health-Disease Relationship: The Importance of Consuming Probiotics and Prebiotics. Foods 2021, 10(6).
  15. Vieira, A.T.; Fukumori, C.; Ferreira, C.M. New insights into therapeutic strategies for gut microbiome modulation in inflammatory diseases. Clin. Transl. Immunol. 2016, 5(6), e87.
  16. Liu, W.Y.; Lu, D.J.; Du, X.M.; et al. Effect of aerobic exercise and low carbohydrate diet on prediabetic nonalcoholic fatty liver disease in postmenopausal women and middle aged men – the role of gut microbiota composition: study protocol for the AELC randomized controlled trial. BMC Public Health 2014, 14, 48.
  17. Gu, X.; Lu, Q.; Zhang, C.; et al. Clinical Application and Progress of Fecal Microbiome Transplantation in Liver Diseases: A Review. Semin. Liver Dis. 2021, 41, 495–506.
  18. Stojic, J.; Kukla, M.; Grgurevic, I. The Intestinal Microbiome in the Development of Chronic Liver Disease: Current Status. Diagnostics 2023, 13.
  19. Won, S.M.; Park, E.; Jeong, J.J.; et al. The Gut Microbiome-Derived Immune Response in Chronic Liver Disease. Int. J. Mol. Sci. 2021, 22.
  20. Yadegar, A.; Pakpour, S.; Ibrahim, F.F.; et al. Beneficial effects of fecal microbiome transplantation in recurrent Clostridioides difficile infection. Cell Host Microbe 2023, 31, 695–711.
  21. Valentin-Cortez, F.J.; Córdova-Gallardo, J.; Méndez-Sánchez, N. Narrative review of gut microbiome and liver diseases: facts and fictions. Dig. Med. Res. 2022, 5.
  22. Llorente, C.; Schnabl, B. The gut microbiome and liver disease. Cell. Mol. Gastroenterol. Hepatol. 2015, 1, 275–284.
  23. Paolella, G.; Mandato, C.; Pierri, L.; et al. Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease. World J. Gastroenterol. 2014, 20, 15518–15531.
  24. Le Roy, T.; Llopis, M.; Lepage, P.; et al. Intestinal microbiome determines development of non-alcoholic fatty liver disease in mice. Gut 2013, 62, 1787–1794.
  25. Gómez-Hurtado, I.; Gallego-Durán, R.; Zapater, P.; et al. Bacterial antigen translocation and age as BMI-independent contributing factors on systemic inflammation in NAFLD patients. Liver Int. 2020, 40, 2182–2193.
  26. Wahlström, A. Outside the liver box: The gut microbiome as pivotal modulator of liver diseases. Biochim. Biophys. Acta Mol. Basis Dis. 2019, 1865, 912–919.
  27. Khan, A.; Ding, Z.; Ishaq, M.; et al. Understanding the Effects of Gut Microbiome Dysbiosis on Nonalcoholic Fatty Liver Disease and the Possible Probiotics Role: Recent Updates. Int. J. Biol. Sci. 2021, 17, 818–833.
  28. Zhang, Y., Ma, C., Liu, C., et al. Combined effects of vitamin D and omega-3 fatty acids on gut microbiota and NAFLD improvement: Evidence from a randomized controlled trial. Nutrients 2021, 13, 2681.
  29. Özdirik, B.; Müller, T.; Wree, A.; et al. The Role of Microbiome in Primary Sclerosing Cholangitis and Related Biliary Malignancies. Int. J. Mol. Sci. 2021, 22.
  30. Boursier, J.; Mueller, O.; Barret, M.; et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiome. Hepatology 2016, 63, 764–775.
  31. Lin, M.J.; Su, T.H.; Chen, C.C.; et al. Diversity and composition of gut microbiome in healthy individuals and patients at different stages of hepatitis B virus-related liver disease. Gut Pathog. 2023, 15, 24.
  32. Li, Y.G.; Yu, Z.J.; Li, A.; et al. Gut microbiome alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions. World J. Gastroenterol. 2022, 28, 3555–3572.
  33. Wang, Y.; Pan, C.Q.; Xing, H. Advances in Gut Microbiome of Viral Hepatitis Cirrhosis. Biomed. Res. Int. 2019, 2019, 9726786.
  34. Sparfel, L.; Ratodiarivony, S.; Boutet-Robinet, E.; et al. Akkermansia muciniphila and Alcohol-Related Liver Diseases. A Systematic Review. Mol Nutr Food Res 2024, 68, 1–12.
  35. Ebrahimzadeh Leylabadlo, H.; Sanaie, S.; Sadeghpour Heravi, F.; et al. From role of gut microbiome to microbial-based therapies in type 2-diabetes. Infect. Genet. Evol. 2020, 81, 104268.
  36. Zafari, N.; Velayati, M.; Fahim, M.; et al. Role of gut bacterial and non-bacterial microbiome in alcohol-associated liver disease: Molecular mechanisms, biomarkers, and therapeutic prospective. Life Sci. 2022, 305, 120760.
  37. Mattner, J. Impact of Microbes on the Pathogenesis of Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC). Int. J. Mol. Sci. 2016, 17.
  38. Chen, W.; Wei, Y.; Xiong, A.; et al. Comprehensive Analysis of Serum and Fecal Bile Acid Profiles and Interaction with Gut Microbiome in Primary Biliary Cholangitis. Clin. Rev. Allergy Immunol. 2020, 58, 25–38.
  39. Usami, M.; Miyoshi, M.; Yamashita, H. Gut microbiome and host metabolism in liver cirrhosis. World J. Gastroenterol. 2015, 21, 11597–11608.
  40. Rai, R.; Saraswat, V.A.; Dhiman, R.K. Gut microbiome: its role in hepatic encephalopathy. J. Clin. Exp. Hepatol. 2015, 5, S29–S36.
  41. Won, S.M.; Oh, K.K.; Gupta, H.; et al. The Link between Gut Microbiome and Hepatic Encephalopathy. Int. J. Mol. Sci. 2022, 23.
  42. Zhu, R.; Liu, L.; Zhang, G.; et al. The pathogenesis of gut microbiome in hepatic encephalopathy by the gut-liver-brain axis. Biosci. Rep. 2023, 43.
  43. Stojic, J.; Kukla, M.; Grgurevic, I. The Intestinal Microbiome in the Development of Chronic Liver Disease: Current Status. Diagnostics 2023, 13, 2960.
  44. Kalambokis, G.; Tsianos, E.V. Endotoxaemia in the pathogenesis of cytopenias in liver cirrhosis. Could oral antibiotics raise blood counts? Med. Hypotheses 2011, 76, 105–109.
  45. Mancini, A.; Campagna, F.; Amodio, P.; et al. Gut:liver:brain axis: the microbial challenge in the hepatic encephalopathy. Food Funct. 2018, 9, 1373–1388.
  46. Ding, J.H.; Jin, Z.; Yang, X.X.; et al. Role of gut microbiome via the gut-liver-brain axis in digestive diseases. World J. Gastroenterol. 2020, 26, 6141–6162.
  47. Bellafante, D.; Gioia, S.; Faccioli, J.; et al. Old and New Precipitants in Hepatic Encephalopathy: A New Look at a Field in Continuous Evolution. J. Clin. Med. 2023, 12.
  48. Kang, D.J.; Betrapally, N.S.; Ghosh, S.A.; et al. Gut microbiome drive the development of neuroinflammatory response in cirrhosis in mice. Hepatology 2016, 64, 1232–1248.
  49. Bajaj, J.S.; Fagan, A.; White, M.B.; et al. Specific Gut and Salivary Microbiome Patterns Are Linked With Different Cognitive Testing Strategies in Minimal Hepatic Encephalopathy. Am. J. Gastroenterol. 2019, 114, 1080–1090.
  50. Quigley, E.M.M.; Stanton, C.; Murphy, E.F. The gut microbiome and the liver. Pathophysiological and clinical implications. J. Hepatol. 2013, 58, 1020–1027.
  51. Solé, C.; Guilly, S.; Da Silva, K.; et al. Alterations in Gut Microbiome in Cirrhosis as Assessed by Quantitative Metagenomics: Relationship With Acute-on-Chronic Liver Failure and Prognosis. Gastroenterology 2021, 160, 206–218.
  52. Nie, G.; Zhang, H.; Xie, D.; et al. Liver cirrhosis and complications from the perspective of dysbiosis. Front. Med. 2023, 10, 1320015.
  53. Agrinier, A.L.; Morissette, A.; Daoust, L.; et al. Camu-camu decreases hepatic steatosis and liver injury markers in overweight, hypertriglyceridemic individuals: A randomized crossover trial. Cell Rep. Med. 2024, 5, 101682.
  54. Jin, Y.; Wang, X.; Chen, K.; et al. Silymarin decreases liver stiffness associated with gut microbiome in patients with metabolic dysfunction-associated steatotic liver disease: a randomized, double-blind, placebo-controlled trial. Lipids Health Dis. 2024, 23, 239.
  55. Lin, J.H.; Lin, C.H.; Kuo, Y.W.; et al. Probiotic Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 improved liver function and uric acid management-A pilot study. PLoS ONE 2024, 19, e0307181.
  56. Tian, S.; Lei, Y.; Zhao, F.; et al. Improving insulin resistance by sulforaphane via activating the Bacteroides and Lactobacillus SCFAs-GPR-GLP1 signal axis. Food Funct. 2024, 15, 8644–8660.
  57. Reshef, N.; Gophna, U.; Reshef, L.; et al. Prebiotic Treatment in Patients with Nonalcoholic Fatty Liver Disease (NAFLD)-A Randomized Pilot Trial. Nutrients 2024, 16.
  58. He, Y.; Chen, X.; Li, Y.; et al. Curcumin supplementation alleviates hepatic fat content associated with modulation of gut microbiome-dependent bile acid metabolism in patients with nonalcoholic simple fatty liver disease: a randomized controlled trial. Am. J. Clin. Nutr. 2024, 120, 66–79.
  59. Liu, Q.; Li, X.; Pan, Y.; et al. Efficacy and safety of Qushi Huayu, a traditional Chinese medicine, in patients with nonalcoholic fatty liver disease in a randomized controlled trial. Phytomedicine 2024, 130, 155398.
  60. Li, X.; Pan, C.; Ma, W.; et al. Effects of dietary supplementation of fish oil plus vitamin D(3) on gut microbiome and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial. Food Funct. 2024, 15, 2616–2627.
  61. Ni, Y.; Qian, L.; Siliceo, S.L.; et al. Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations. Cell Metab. 2023, 35, 1530–1547.
  62. Gómez-Pérez, A.M.; Ruiz-Limón, P.; Salas-Salvadó, J.; et al. Gut microbiome in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis. Gut Microbes 2023, 15, 2223339.
  63. Escouto, G.S.; Port, G.Z.; Tovo, C.V.; et al. Probiotic Supplementation, Hepatic Fibrosis, and the Microbiome Profile in Patients with Nonalcoholic Steatohepatitis: A Randomized Controlled Trial. J. Nutr. 2023, 153, 1984–1993.
  64. He, K.; Guo, L.L.; Tang, H.; et al. A Freshwater Fish-Based Diet Alleviates Liver Steatosis by Modulating Gut Microbiome and Metabolites: A Clinical Randomized Controlled Trial in Chinese Participants With Nonalcoholic Fatty Liver Disease. Am. J. Gastroenterol. 2022, 117, 1621–1631.
  65. Chayanupatkul, M.; Sawatdee, W.; Chutaputti, A.; et al. The Efficacy of Oligonol in Nonalcoholic Fatty Liver Disease: A Randomized Double-Blinded Placebo-Controlled Trial. J. Integr. Complement. Med. 2022, 28, 904–908.
  66. Xue, L.; Deng, Z.; Luo, W.; et al. Effect of Fecal Microbiome Transplantation on Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial. Front. Cell. Infect. Microbiol. 2022, 12, 759306.
  67. Manzhalii, E.; Moyseyenko, V.; Kondratiuk, V.; et al. Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment. World J. Hepatol. 2022, 14, 634–646.
  68. Calabrese, F.M.; Disciglio, V.; Franco, I.; et al. A Low Glycemic Index Mediterranean Diet Combined with Aerobic Physical Activity Rearranges the Gut Microbiome Signature in NAFLD Patients. Nutrients 2022, 14.
  69. Cheng, R.; Wang, L.; Le, S.; et al. A randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease. Nat. Commun. 2022, 13, 2555.
  70. Amadieu, C.; Coste, V.; Neyrinck, A.M.; et al. Restoring an adequate dietary fiber intake by inulin supplementation: a pilot study showing an impact on gut microbiome and sociability in alcohol use disorder patients. Gut Microbes 2022, 14, 2007042.
  71. Mohamad Nor, M.H.; Ayob, N.; Mokhtar, N.M.; et al. The Effect of Probiotics (MCP(®) BCMC(®) Strains) on Hepatic Steatosis, Small Intestinal Mucosal Immune Function, and Intestinal Barrier in Patients with Non-Alcoholic Fatty Liver Disease. Nutrients 2021, 13.
  72. Patel, V.C.; Lee, S.; McPhail, M.J.W.; et al. Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial. J. Hepatol. 2022, 76, 332–342.
  73. Amerikanou, C.; Kanoni, S.; Kaliora, A.C.; et al. Effect of Mastiha supplementation on NAFLD: The MAST4HEALTH Randomised, Controlled Trial. Mol. Nutr. Food Res. 2021, 65, e2001178.
  74. Traussnigg, S.; Halilbasic, E.; Hofer, H.; et al. Open-label phase II study evaluating safety and efficacy of the non-steroidal farnesoid X receptor agonist PX-104 in non-alcoholic fatty liver disease. Wien. Klin. Wochenschr. 2021, 133, 441–451.
  75. Bajaj, J.S.; Gavis, E.A.; Fagan, A.; et al. A Randomized Clinical Trial of Fecal Microbiome Transplant for Alcohol Use Disorder. Hepatology 2021, 73, 1688–1700.
  76. Jian, C.; Luukkonen, P.; Sädevirta, S.; et al. Impact of short-term overfeeding of saturated or unsaturated fat or sugars on the gut microbiome in relation to liver fat in obese and overweight adults. Clin. Nutr. 2021, 40, 207–216.
  77. Zhuo, L.; Xu, J.; You, N.; et al. Study on the new strategy and key techniques for accurate prevention and treatment of nonalcoholic steatohepatitis based on intestinal target bacteria. Medicine 2020, 99, e22867.
  78. van Trijp, M.P.H.; Schutte, S.; et al. Minor Changes in the Composition and Function of the Gut Microbiome During a 12-Week Whole Grain Wheat or Refined Wheat Intervention Correlate with Liver Fat in Overweight and Obese Adults. J. Nutr. 2021, 151, 491–502.
  79. Loomba, R.; Ling, L.; Dinh, D.M.; et al. The Commensal Microbe Veillonella as a Marker for Response to an FGF19 Analog in NASH. Hepatology 2021, 73, 126–143.
  80. Quiroga, R.; Nistal, E.; Estébanez, B.; et al. Exercise training modulates the gut microbiome profile and impairs inflammatory signaling pathways in obese children. Exp. Mol. Med. 2020, 52, 1048–1061.
  81. Craven, L.; Rahman, A.; Nair Parvathy, S.; et al. Allogenic Fecal Microbiome Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial. Am. J. Gastroenterol. 2020, 115, 1055–1065.
  82. Chong, C.Y.L.; Orr, D.; Plank, L.D.; et al. Randomised Double-Blind Placebo-Controlled Trial of Inulin with Metronidazole in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients 2020, 12.
  83. Scorletti, E.; Afolabi, P.R.; Miles, E.A.; et al. Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2020, 158, 1597–1610.
  84. Huber, Y.; Pfirrmann, D.; Gebhardt, I.; et al. Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program. Aliment. Pharmacol. Ther. 2019, 50, 930–939.
  85. Chen, Y.; Feng, R.; Yang, X.; et al. Yogurt improves insulin resistance and liver fat in obese women with nonalcoholic fatty liver disease and metabolic syndrome: a randomized controlled trial. Am. J. Clin. Nutr. 2019, 109, 1611–1619.
  86. Bajaj, J.S.; Salzman, N.H.; Acharya, C.; et al. Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial. Hepatology 2019, 70, 1690–1703.
  87. Chambers, E. S., Byrne, C. S., Morrison, D. J., et al. Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial. Gut 2019, 68, 1430–1438.
  88. Ahn, S.B.; Jun, D.W.; Kang, B.K.; et al. Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease. Sci. Rep. 2019, 9, 5688.
  89. Allegretti, J.R.; Kassam, Z.; Carrellas, M.; et al. Fecal Microbiome Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial. Am. J. Gastroenterol. 2019, 114, 1071–1079.
  90. Chashmniam, S.; Mirhafez, S.R.; Dehabeh, M.; et al. A pilot study of the effect of phospholipid curcumin on serum metabolomic profile in patients with non-alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled trial. Eur. J. Clin. Nutr. 2019, 73, 4–1235.
  91. Schutte, S.; Esser, D.; Hoevenaars, F.P.M.; et al. A 12-wk whole-grain wheat intervention protects against hepatic fat: the Graandioos study, a randomized trial in overweight subjects. Am. J. Clin. Nutr. 2018, 108, 1264–1274.
  92. Tenorio-Jiménez, C.; Martínez-Ramírez, M.J.; Tercero-Lozano, M.; et al. Evaluation of the effect of Lactobacillus reuteri V3401 on biomarkers of inflammation, cardiovascular risk and liver steatosis in obese adults with metabolic syndrome: a randomized clinical trial (PROSIR). BMC Complement. Altern. Med. 2018, 18, 306.
  93. Kobyliak, N.; Abenavoli, L.; Falalyeyeva, T.; et al. Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study. Minerva Med. 2018, 109, 418–428.
  94. Bajaj, J.S.; Matin, P.; White, M.B.; et al. Periodontal therapy favorably modulates the oral-gut-hepatic axis in cirrhosis. Am. J. Physiol. Gastrointest. Liver Physiol. 2018, 315, G824–G837.
  95. Scorletti, E.; Afolabi, P.R.; Miles, E.A.; et al. Design and rationale of the INSYTE study: A randomised, placebo controlled study to test the efficacy of a synbiotic on liver fat, disease biomarkers and intestinal microbiome in non-alcoholic fatty liver disease. Contemp. Clin. Trials 2018, 71, 113–123.
  96. Kobyliak, N.; Abenavoli, L.; Mykhalchyshyn, G.; et al. A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. J Gastrointest Liver Dis 2018, 27, 41–49.
  97. Manzhalii, E.; Virchenko, O.; Falalyeyeva, T.; et al. Treatment efficacy of a probiotic preparation for non-alcoholic steatohepatitis: A pilot trial. J Dig Dis 2017, 18, 698–703.
  98. Sherf-Dagan, S.; Zelber-Sagi, S.; Zilberman-Schapira, G.; et al. Probiotics administration following sleeve gastrectomy surgery: a randomized double-blind trial. Int J Obes 2018, 42, 147–155.
  99. Bajaj, J.S.; Kassam, Z.; Fagan, A.; et al. Fecal microbiome transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology 2017, 66, 1727–1738.
  100. Ferolla, S.M.; Couto, C.A.; Costa-Silva, L.; et al. Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis. Nutrients 2016, 8, 1–11.
  101. Lambert, J.E.; Parnell, J.A.; Eksteen, B.; et al. Gut microbiome manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol. BMC Gastroenterol 2015, 15, 169.
  102. Engstler, A.J.; Aumiller, T.; Degen, C.; et al. Insulin resistance alters hepatic ethanol metabolism: studies in mice and children with non-alcoholic fatty liver disease. Gut 2016, 65, 1564–1571.
  103. Kwak, D.S.; Jun, D.W.; Seo, J.G.; et al. Short-term probiotic therapy alleviates small intestinal bacterial overgrowth, but does not improve intestinal permeability in chronic liver disease. Eur J Gastroenterol Hepatol 2014, 26, 1353–1359.
  104. Alisi, A.; Bedogni, G.; Baviera, G.; et al. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2014, 39, 1276–1285.
  105. Liu, W.Y.; Lu, D.J.; Du, X.M.; et al. Effect of aerobic exercise and low carbohydrate diet on pre-diabetic non-alcoholic fatty liver disease in postmenopausal women and middle aged men--the role of gut microbiome composition: study protocol for the AELC randomized controlled trial. BMC Public Health 2014, 14, 48.
  106. Lunia, M.K.; Sharma, B.C.; Sharma, P.; et al. Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial. Clin Gastroenterol Hepatol 2014, 12, 1003–1008.
  107. Jayakumar, S.; Carbonneau, M.; Hotte, N.; et al. VSL#3 ® probiotic therapy does not reduce portal pressures in patients with decompensated cirrhosis. Liver Int 2013, 33, 1470–1477.
  108. Zoghi, S.; Abbasi, A.; Heravi, F.; et al. The gut microbiome and celiac disease: Pathophysiology, current perspective and new therapeutic approaches. Crit Rev Food Sci Nutr 2022, 64, 1–21.
  109. Hevia, A.; Delgado, S.; Margolles, A.; et al. Application of density gradient for the isolation of the fecal microbial stool component and the potential use thereof. Sci Rep 2015, 5, 16807.
  110. Du, C.; Luo, Y.; Walsh, S.; et al. Oral Fecal Microbiome Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2021, 55, 300–308.
  111. Mohan, B.P.; Loganathan, P.; Khan, S.R.; et al. Fecal microbiome transplant delivered via invasive routes in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials. Indian J Gastroenterol 2023, 42, 315–323.
  112. Burz, S.D.; Monnoye, M.; Philippe, C.; et al. Fecal Microbiome Transplant from Human to Mice Gives Insights into the Role of the Gut Microbiome in Non-Alcoholic Fatty Liver Disease (NAFLD). Microorganisms 2021, 9, 1–14.
  113. van Beurden, Y.H.; Nieuwdorp, M.; van de Berg, P.; et al. Current challenges in the treatment of severe Clostridium difficile infection: early treatment potential of fecal microbiome transplantation. Therap Adv Gastroenterol 2017, 10, 373–381.
  114. Falconer, S.; Moss, E.; Andermann, T.; et al. Fecal Microbiome Transplant Is a Potentially Safe and Effective Treatment for Clostridium Difficile Infection in Hematopoietic Stem Cell Recipients. Biol Blood Marrow Transplant 2016, 22, S53–S54.
  115. Porcari, S.; Severino, A.; Rondinella, D.; Bibbò, S.; et al. Fecal microbiome transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis. J Autoimmun 2023, 141, 103033.
  116. Belvoncikova, P.; Maronek, M.; Gardlik, R. Gut Dysbiosis and Fecal Microbiome Transplantation in Autoimmune Diseases. Int J Mol Sci 2022, 23, 1–19.
  117. Feng, J.; Chen, Y.; Liu, Y.; et al. Efficacy and safety of fecal microbiome transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis. Sci Rep 2023, 13, 14494.
  118. Airola, C.; Severino, A.; Porcari, S.; et al. Future Modulation of Gut Microbiome: From Eubiotics to FMT, Engineered Bacteria, and Phage Therapy. Antibiotics 2023, 12, 1–18.
  119. Cammarota, G.; Ianiro, G.; Gasbarrini, A. Fecal microbiome transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol 2014, 48, 693–702.
  120. DeFilipp, Z.; Bloom, P.P.; Soto, M.T.; et al. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiome Transplant. N Engl J Med 2019, 381, 2043–2050.
  121. Moayyedi, P.; Surette, M.G.; Kim, P.T.; et al. Fecal Microbiome Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology 2015, 149, 102–109.
  122. Yu, E.W.; Gao, L.; Stastka, P.; et al. Fecal microbiota transplantation for the treatment of obesity and metabolic syndrome: A randomized double-blind placebo-controlled pilot trial. PLOS Medicine 2020, 17, e1003051.
  123. Pérez-Montes de Oca, A.; Julián, M.T.; Ramos, A.; et al. Microbiome, Fiber, and NAFLD: Is There Any Connection? Nutrients 2020, 12, 1–14.
  124. Zhou, X.; Wang, J.; Zhou, S.; et al. Efficacy of probiotics on nonalcoholic fatty liver disease: A meta-analysis. Medicine 2023, 102, e32734.
  125. Wang, Y.; Wang, Y.; Sun, J. The clinical effect of probiotics on patients with non-alcoholic fatty liver disease: a meta-analysis. Bioengineered 2022, 13, 14960–14973.
  126. Al-Muzafar, H.M.; Amin, K.A. Probiotic mixture improves fatty liver disease by virtue of its action on lipid profiles, leptin, and inflammatory biomarkers. BMC Complement Altern Med 2017, 17, 43.
  127. Fasshauer, M.; Blüher, M. Adipokines in health and disease. Trends Pharmacol Sci 2015, 36, 461–470.
  128. Polyzos, S.A.; Kountouras, J.; Mantzoros, C.S. Adipokines in nonalcoholic fatty liver disease. Metabolism 2016, 65, 1062–1079.
  129. Behrouz, V.; Jazayeri, S.; Aryaeian, N.; et al. Effects of Probiotic and Prebiotic Supplementation on Leptin, Adiponectin, and Glycemic Parameters in Non-alcoholic Fatty Liver Disease: A Randomized Clinical Trial. Middle East J Dig Dis 2017, 9, 150–157.
  130. Paschos, P.; Paletas, K. Non alcoholic fatty liver disease and metabolic syndrome. Hippokratia 2009, 13, 9–19.
  131. Yu, S.J.; Kim, W.; Kim, D.; et al. Visceral Obesity Predicts Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Medicine 2015, 94, e2159.
  132. Choi, H.H.; Cho, Y.-S. Fecal Microbiome Transplantation: Current Applications, Effectiveness, and Future Perspectives. Clin. Endosc. 2016, 49, 257–265.
  133. Schwenger, K.J.; Clermont-Dejean, N.; Allard, J.P. The role of the gut microbiome in chronic liver disease: the clinical evidence revised. JHEP Rep. 2019, 1, 214–226.
  134. Lungosi, M.B.; Muzembo, B.A.; Mbendi, N.C.; et al. Assessing the prevalence of hepatitis B virus infection among health care workers in a referral hospital in Kisantu, Congo DR: a pilot study. Ind Health 2019, 57, 621–626.
  135. Kassa, Y.; Million, Y.; Gedefie, A.; et al. Alteration of Gut Microbiome and Its Impact on Immune Response in Patients with Chronic HBV Infection: A Review. Infect Drug Resist 2021, 14, 2571–2578.
  136. Gish, R.G.; Lok, A.S.; Chang, T.T.; et al. Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B. Gastroenterology 2007, 133, 1437–1444.
  137. Tujios, S.; Stravitz, R.T.; Lee, W.M. Management of Acute Liver Failure: Update 2022. Semin Liver Dis 2022, 42, 362–378.
  138. Chauhan, A.; Kumar, R.; Sharma, S.; et al. Fecal Microbiome Transplantation in Hepatitis B e Antigen-Positive Chronic Hepatitis B Patients: A Pilot Study. Dig Dis Sci 2021, 66, 873–880.
  139. Ren, Y.D.; Ye, Z.S.; Yang, L.Z.; et al. Fecal microbiome transplantation induces hepatitis B virus e‐antigen (HBeAg) clearance in patients with positive HBeAg after long‐term antiviral therapy. Hepatology 2017, 65, 1765–1768.
  140. Leylabadlo, H.E.; Kafil, H.S.; Farajnia, S.; et al. Gut microbiome in nonalcoholic fatty liver diseases with and without type-2 diabetes mellitus. Eur J Gastroenterol Hepatol 2021, 33, e548–e554.
  141. Behzadi, E.; Hosseini, H.M.; Fooladi, A.A.I. The inhibitory impacts of Lactobacillus rhamnosus GG-derived extracellular vesicles on the growth of hepatic cancer cells. Microb Pathog 2017, 110, 1–6.