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Aug 7, 2024
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Sep 19, 2024
Published
Sep 30, 2024
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Abstract

Gut microbiome is essential in maintaining metabolism, gut barrier homeostasis, inflammation, and hematopoiesis. Several factors affect gut microbiome composition, including genetics, lifestyle, external factors, and disease. Cholestasis liver disease promotes gut dysbiosis via abnormal bile production or flow to the intestine and disrupts the gut microbiome. This condition leads to intestinal leakage, which enables bacterial and endotoxin translocation to the liver through the portal vein. Bacterial translocation promotes inflammatory responses, which worsen liver damage in cholestasis. Moreover, probiotic supplementation in other diseases has been shown to preserve gut microbiome composition. While such studies have documented probiotics' beneficial effects, no adequate clinical trials support probiotics' potency as a cholestasis treatment. Hence, this systematic review aims to provide an in-depth analysis of probiotic supplementation as a therapy for cholestasis liver disease in animal models. The search strategies were conducted based on PRISMA methodologies based on various academic literature. The selected studies have shown improvements in bile acid metabolism, microbiota-gut-liver axis, gut epithelium integrity, liver damage and inflammation response, and liver fibrosis progression, which need to be confirmed in human clinical trials.

Keywords

Bile acid Cholestasis Gut Microbiome Probiotic Liver Injury

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1.
Azizah N, Oswari H, Sjatha F. The Effect of Probiotic Supplementation in Cholestasis Liver Disease: A Systematic Review of Animal Studies. EKSAKTA [Internet]. 2024Sep.30 [cited 2025Apr.26];25(03):334-52. Available from: https://eksakta.ppj.unp.ac.id/index.php/eksakta/article/view/533

References

  1. Athanasopoulou, K., Adamopoulos, P. G., and Scorilas, A. (2023). Unveiling the Human Gastrointestinal Tract Microbiome: The Past, Present, and Future of Metagenomics. Biomedicines. 11(3), 1–16.
  2. Afzaal, M., Saeed, F., Shah, Y. A., Hussain, M., Rabail, R., Socol, C. T., et al. (2022). Human gut microbiota in health and disease: Unveiling the relationship. Frontiers in Microbiology, 13, 1–14.
  3. Wang, L., Cao, Z. M., Zhang, L. L., Li, J. M., and Lv, W. L. (2022). The Role of Gut Microbiota in Some Liver Diseases: From an Immunological Perspective. Frontiers in Immunology, 13, 1–17.
  4. Wang, P. X., Deng, X. R., Zhang, C. H., and Yuan, H. J. (2020). Gut microbiota and metabolic syndrome. Chinese Medical Journal,133(7), 808–816.
  5. Al Samarraie, A., Pichette, M., and Rousseau, G. (2023). Role of the Gut Microbiome in the Development of Atherosclerotic Cardiovascular Disease. International Journal of Molecular Sciences, 24(6), 1–17.
  6. Xie, S., Wei, S., Ma, X., Wang, R., He, T., Zhang, Z., et al. (2023). Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis. Frontiers in Pharmacology, 14, 1–27.
  7. Feldman, A. G. and Sokol, R. J. (2021). Neonatal Cholestasis: Updates on Diagnostics, Therapeutics, and Prevention. NeoReviews,22(12), E819–E836.
  8. Wang, H., Yang, L., and Wang, J. (2022). Etiology of neonatal cholestasis after emerging molecular diagnostics. Translational Pediatrics, 11(3), 359–367.
  9. Li, T. and Apte, U. (2015). Bile Acid Metabolism and Signaling in Cholestasis, Inflammation, and Cancer. in: Adv Pharmacol, Academic Press Inc., pp. 263–302.
  10. Zou, M., Wang, A., Wei, J., Cai, H., Yu, Z., Zhang, L., et al. (2021). An insight into the mechanism and molecular basis of dysfunctional immune response involved in cholestasis. International Immunopharmacology, 92, 1–13.
  11. Jiang, B., Yuan, G., Wu, J., Wu, Q., Li, L., and Jiang, P. (2022). Prevotella copri ameliorates cholestasis and liver fibrosis in primary sclerosing cholangitis by enhancing the FXR signalling pathway. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease,1868(3), 1–12.
  12. Fleishman, J. S. and Kumar, S. (2024). Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets. Signal Transduction and Targeted Therapy, 9(1), 1–51.
  13. Ticho, A.L., Malhotra, P., Dudeja, P. K., Gill, R. K., and Alrefai, W. A. (2019). Bile acid receptors and gastrointestinal functions. Liver Research, 3(1), 31–39.
  14. Han, S., Wang, K., Shen, J., Xia, H., Lu, Y., Zhuge, A., et al. (2023). Probiotic Pediococcus pentosaceus Li05 Improves Cholestasis through the FXR-SHP and FXR-FGF15 Pathways. Nutrients, 15(23), 1–16.
  15. Sun, H., Su, X., Liu, Y., Li, G., and Du, Q. (2023). Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats. Iscience, 26(12), 1–17.
  16. Kummen, M., Thingholm, L. B., Rühlemann, M. C., Holm, K., Hansen, S. H., Moitinho-Silva, L., et al. (2021). Altered Gut Microbial Metabolism of Essential Nutrients in Primary Sclerosing Cholangitis. Gastroenterology, 160(5), 1784-1798.e0.
  17. Song, W., Sun, L. Y., Zhu, Z. J., Wei, L., Qu, W., Zeng, Z. G., et al. (2021). Association of Gut Microbiota and Metabolites With Disease Progression in Children With Biliary Atresia. Frontiers in Immunology, 12, 1–11.
  18. Jiang, X. W., Li, Y. T., Ye, J. Z., Lv, L. X., Yang, L. Y., Bian, X. Y., et al. (2020). New strain of Pediococcus pentosaceus alleviates ethanol-induced liver injury by modulating the gut microbiota and short-chain fatty acid metabolism. World Journal of Gastroenterology, 26(40), 6224–6240.
  19. Cao, F., Ding, Q., Zhuge, H., Lai, S., Chang, K., Le, C., et al. (2023). Lactobacillus plantarum ZJUIDS14 alleviates non-alcoholic fatty liver disease in mice in association with modulation in the gut microbiota. Frontiers in Nutrition, 9, 1–16.
  20. Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., et al. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. The BMJ, 372, 1–9.
  21. Schiavenato, M. and Chu, F. (2021). PICO: What it is and what it is not. Nurse Education in Practice, 56, 1–3.
  22. Hooijmans, C. R., Rovers, M. M., De Vries, R. B. M., Leenaars, M., Ritskes-Hoitinga, M., and Langendam, M. W. (2014).SYRCLE’s risk of bias tool for animal studies. BMC Medical Research Methodology, 14(1), 1–9.
  23. Tidwell, J. and Wu, G. Y. (2024). Heritable Chronic Cholestatic Liver Diseases: A Review. Journal of Clinical and Translational Hepatology, 12(8), 726–738
  24. Lu, L. (2022). Guidelines for the Management of Cholestatic Liver Diseases (2021). Journal of Clinical and Translational Hepatology, 10(4), 757–769.
  25. Tsai, M. T. and Tarng, D. C. (2019). Beyond a measure of liver function—bilirubin acts as a potential cardiovascular protector in chronic kidney disease patients. International Journal of Molecular Sciences, 20(1), 1–19.
  26. Sumida, K., Kawana, M., Kouno, E., Itoh, T., Takano, S., Narawa, T., et al. (2013). Importance of UDP-glucuronosyltransferase 1A1 expression in skin and its induction by UVB in neonatal hyperbilirubinemias. Molecular Pharmacology, 84(5), 679–686.
  27. Guerra Ruiz, A. R., Crespo, J., López Martínez, R. M., Iruzubieta, P., Casals Mercadal, G., Lalana Garcés, M., et al. (2021).Measurement and clinical usefulness of bilirubin in liver disease. Advances in Laboratory Medicine, 2(3), 352–361.
  28. Kriegermeier, A. and Green, R. (2020). Pediatric Cholestatic Liver Disease: Review of Bile Acid Metabolism and Discussion of Current and Emerging Therapies. Frontiers in Medicine, 7, 1–15.
  29. Mavila, N., Siraganahalli Eshwaraiah, M., and Kennedy, J. (2024). Ductular Reactions in Liver Injury, Regeneration, and Disease Progression—An Overview. Cells, 13(7), 1–19.
  30. Ainosah, R. H., Hagras, M. M., Alharthi, S. E., and Saadah, O. I. (2020). The effects of ursodeoxycholic acid on sepsis-induced cholestasis management in an animal model. Journal of Taibah University Medical Sciences, 15(4), 312–320.
  31. Kong, Y., Li, M., Wu, X., Xia, C., Liu, X., and Wang, G. (2022). Protective mechanism of homologous lactic acid bacteria against cholestatic liver injury in snakehead fish. Aquaculture. 550(2022), 1–13.
  32. Ren, L., Song, Q., Liu, Y., Zhang, L., Hao, Z., and Feng, W. (2019). Probiotic Lactobacillus rhamnosus GG prevents progesterone metabolite epiallaopregnanolone sulfate-induced hepatic bile acid accumulation and liver injury. Biochemical and Biophysical Research Communications, 520(1), 67–72.
  33. Lin, Q. -X., Huang, W. -W., Shen, W., Deng, X. -S., Tang, Z.- Y., Chen, Z. -H., et al. (2022). Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota. Frontiers in Immunology, 13, 1–14.
  34. Liu, Y., Chen, K., Li, F., Gu, Z., Liu, Q., He, L., et al. (2020). Probiotic Lactobacillus rhamnosus GG Prevents Liver Fibrosis Through Inhibiting Hepatic Bile Acid Synthesis and Enhancing Bile Acid Excretion in Mice. Hepatology., 71(6), 2050–2066.
  35. Kabiri-Arani, S., Motallebi, M., Taheri, M. A., Kheiripour, N., Ardjmand, A., Aghadavod, E., et al. (2024). The Effect of Heat-Killed Lactobacillus plantarum on Oxidative Stress and Liver Damage in Rats with Bile Duct Ligation-Induced Hepatic Fibrosis. Probiotics and Antimicrobial Proteins, 16(1), 196–211.
  36. Luo, X. and Lu, L. G. (2024). Progress in the Management of Patients with Cholestatic Liver Disease: Where Are We and Where Are We Going? Journal of Clinical and Translational Hepatology, 12(6), 581–588.
  37. Ahmed, M. (2022). Functional, Diagnostic and Therapeutic Aspects of Bile. Clinical and Experimental Gastroenterology, 15, 105–120.
  38. Mazziotta, C., Tognon, M., Martini, F., Torreggiani, E., and Rotondo, J. C. (2023). Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells, 12(1), 1–33.
  39. Castro, A., Aleman, R. S., Tabora, M., Kazemzadeh, S., Pournaki, L. K., Cedillos, R., et al. (2023). Probiotic Characteristics of Streptococcus thermophilus and Lactobacillus bulgaricus as Influenced by New Food Sources. Microorganisms, 11(9), 1–10.
  40. Stoeva, M. K., Garcia-So, J., Justice, N., Myers, J., Tyagi, S., Nemchek, M., et al. (2021). Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease. Gut Microbes, 13(1), 1–28.
  41. Todorov, S. D., Dioso, C. M., Liong, M. T., Nero, L. A., Khosravi-Darani, K., and Ivanova, I.V. (2023). Beneficial features of pediococcus: from starter cultures and inhibitory activities to probiotic benefits. World Journal of Microbiology and Biotechnology,39(1), 1–20.
  42. Tian, P., Wang, G., Zhao, J., Zhang, H., and Chen, W. (2019). Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis. Journal of Nutritional Biochemistry, 66, 43–51.
  43. Vasconcelos, J. A., Mota, A. S., Olímpio, F., Rosa, P. C., Damaceno-Rodrigues, N., de Paula Vieira, R., et al. (2023). Lactobacillus rhamnosus Modulates Lung Inflammation and Mitigates Gut Dysbiosis in a Murine Model of Asthma-COPD Overlap Syndrome. Probiotics and Antimicrobial Proteins, 1–18.
  44. Yang, T., Yang, H., Heng, C., Wang, H., Chen, S., Hu, Y., et al. (2020). Amelioration of non-alcoholic fatty liver disease by sodium butyrate is linked to the modulation of intestinal tight junctions in db/db mice. Food and Function, 11(12), 10675–10689.
  45. Yoon, S. J., Yu, J. S., Min, B. H., Gupta, H., Won, S. M., Park, H. J., et al. (2023). Bifidobacterium-derived short-chain fatty acids and indole compounds attenuate nonalcoholic fatty liver disease by modulating gut-liver axis. Frontiers in Microbiology, 14, 1–15.
  46. Wang, G., Jiao, T., Xu, Y., Li, D., Si, Q., Hao, J., et al. (2020). Bifidobacterium adolescentis and Lactobacillus rhamnosus alleviate non-alcoholic fatty liver disease induced by a high-fat, high-cholesterol diet through modulation of different gut microbiota-dependent pathways. Food and Function, 11(7), 6115–6127.
  47. Culp, E. J. and Goodman, A. L. (2023). Cross-feeding in the gut microbiome: Ecology and mechanisms. Cell Host and Microbe,31(4), 485–499.
  48. Humbert, L., Maubert, M.A., Wolf, C., Duboc, H., Mahé, M., Farabos, D., et al. (2012). Bile acid profiling in human biological samples: Comparison of extraction procedures and application to normal and cholestatic patients. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 899, 135–145.
  49. Wang, Y., Gao, X., Zhang, X., Xiao, Y., Huang, J., Yu, D., et al. (2019). Gut Microbiota Dysbiosis Is Associated with Altered Bile Acid Metabolism in Infantile Cholestasis. Msystems, 4(6), 1–13.
  50. Tang, B., Tang, L., Li, S., Liu, S., He, J., Li, P., et al. (2023). Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy. Nature Communications, 14(1), 1–17.
  51. Xue, R., Su, L., Lai, S., Wang, Y., Zhao, D., Fan, J., et al. (2021). Bile acid receptors and the gut–liver axis in nonalcoholic fatty liver disease. Cells, 10(11), 1–18.
  52. Stojic, J., Kukla, M., and Grgurevic, I. (2023). The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status. Diagnostics, 13(18), 1–33.
  53. Trebicka, J., Macnaughtan, J., Schnabl, B., Shawcross, D. L., and Bajaj, J. S. (2021). The microbiota in cirrhosis and its role in hepatic decompensation. Journal of Hepatology, 75, S67–S81.
  54. Hiippala, K., Barreto, G., Burrello, C., Diaz-Basabe, A., Suutarinen, M., Kainulainen, V., et al. (2020). Novel Odoribacter splanchnicus Strain and Its Outer Membrane Vesicles Exert Immunoregulatory Effects in vitro. Frontiers in Microbiology, 11, 1–14.
  55. Fusco, W., Lorenzo, M. B., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., et al. (2023). Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota. Nutrients, 15(9), 1–22.
  56. Zheng, F., Wang, Z., Stanton, C., Ross, R. P., Zhao, J., Zhang, H., et al. (2021). Lactobacillus rhamnosus FJSYC4-1 and Lactobacillus reuteri FGSZY33L6 alleviate metabolic syndrome via gut microbiota regulation. Food and Function, 12(9), 3919–3930.
  57. Zhang, T., Li, J., Liu, C. -P., Guo, M., Gao, C. -L., Zhou, L. -P., et al. (2021). Butyrate ameliorates alcoholic fatty liver disease via reducing endotoxemia and inhibiting liver gasdermin D-mediated pyroptosis. Annals of Translational Medicine, 9(10), 873–873.
  58. Zhao, Z. H., Wang, Z. X., Zhou, D., Han, Y., Ma, F., Hu, Z., et al. (2021). Sodium Butyrate Supplementation Inhibits Hepatic Steatosis by Stimulating Liver Kinase B1 and Insulin-Induced Gene. CMGH, 12(3), 857–871.
  59. Cichoz-Lach, H. and Michalak, A. (2014). Oxidative stress as a crucial factor in liver diseases. World Journal of Gastroenterology,20(25), 8082–8091.
  60. Allameh, A., Niayesh-Mehr, R., Aliarab, A., Sebastiani, G., and Pantopoulos, K. (2023). Oxidative Stress in Liver Pathophysiology and Disease. Antioxidants, 12(9), 1–23.
  61. Zhang, I. W., López-Vicario, C., Duran-Güell, M., and Clària, J. (2021). Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts. Frontiers in Molecular Biosciences, 8, 1–15.
  62. Banerjee, P., Gaddam, N., Chandler, V., and Chakraborty, S. (2023). Oxidative Stress–Induced Liver Damage and Remodeling of the Liver Vasculature. American Journal of Pathology, 193(10), 1400–1414.
  63. Delli Bovi, A. P., Marciano, F., Mandato, C., Siano, M. A., Savoia, M., and Vajro, P. (2021). Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review. Frontiers in Medicine, 8, 1–14.
  64. Zhang, M., Wang, X., Zhou, Y., Ma, Y., Shen, T., Chen, H., et al. (2010). Effects of oral Lactobacillus plantarum on hepatocyte tight junction structure and function in rats with obstructive jaundice. Molecular Biology Reports. 37(6), 2989–2999.
  65. Kuo, W. T., Odenwald, M. A., Turner, J. R., and Zuo, L. (2022). Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival. Annals of the New York Academy of Sciences, 1514(1), 21–33.
  66. Jain, P., Batta, A. K., and Singh, P. (2023). Comparative Study of Serum Levels of Gamma-glutamyl Transferase, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), AST:ALT, and Bilirubin in Patients with Chronic Hepatitis. Indian Journal of Medical Biochemistry, 26(3), 73–76.
  67. Mohamed, M.F., Wadhavkar, N., Elfanagely, Y., Marino, D., Beran, A., Abdallah, M., et al. (2023). Etiologies and Outcomes of Transaminase Elevation > 1000 IU/L: A Systematic Review and Meta-Analysis. Digestive Diseases and Sciences, 68(7), 2843–2852.
  68. Gu, Z., Liu, Y., Hu, S., You, Y., Wen, J., Li, W., et al. (2019). Probiotics for alleviating alcoholic liver injury. Gastroenterology Research and Practice, 2019, 1–8.
  69. Leser, T. and Baker, A. (2024). Molecular Mechanisms of Lacticaseibacillus rhamnosus, LGG® Probiotic Function. Microorganisms, 12(4), 1–22.
  70. Javanshir, N., Hosseini, G. N. G., Sadeghi, M., Esmaeili, R., Satarikia, F., Ahmadian, G., et al. (2021). Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System. Biological Procedures Online, 23(1), 1–17.
  71. Yoda, K., Miyazawa, K., Hosoda, M., Hiramatsu, M., Yan, F., and He, F. (2014). Lactobacillus GG-fermented milk prevents DSS-induced colitis and regulates intestinal epithelial homeostasis through activation of epidermal growth factor receptor. European Journal of Nutrition, 53(1), 105–115.
  72. Patilas, C., Varsamos, I., Galanis, A., Vavourakis, M., Zachariou, D., Marougklianis, V., et al. (2024). The Role of Interleukin-10 in the Pathogenesis and Treatment of a Spinal Cord Injury. Diagnostics, 14(2), 1–12.
  73. Antar, S. A., Ashour, N. A., Marawan, M. E., and Al-Karmalawy, A. A. (2023). Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation. International Journal of Molecular Sciences, 24(4), 1–27.
  74. Nishio, T., Koyama, Y., Fuji, H., Ishizuka, K., Iwaisako, K., Taura, K., et al. (2022). The Role of Mesothelin in Activation of Portal Fibroblasts in Cholestatic Liver Injury. Biology, 11(11), 1–17.
  75. Tan, Z., Sun, H., Xue, T., Gan, C., Liu, H., Xie, Y., et al. (2021). Liver Fibrosis: Therapeutic Targets and Advances in Drug Therapy. Frontiers in Cell and Developmental Biology, 9, 1–18.