Journals / Bilecik Şeyh Edebali Üniversitesi Sağlık Bilimleri Fakültesi Dergisi / 2026 / Volume: 4 Issue: 3

The Role of Microbiota and Risk Factors in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Current Findings and Therapeutic Strategies

Alkole Bağlı Olmayan Yağlı Karaciğer Hastalığı Patogenezinde Mikrobiyotanın ve Risk Faktörlerinin Rolü: Güncel Bulgular ve Tedavi Stratejileri

Osman Erkmen(İSTANBUL AREL ÜNİVERSİTESİ)0000-0001-9113-9638
Rabia Melda Karaağaç(İSTANBUL MEDİPOL ÜNİVERSİTESİ, SAĞLIK BİLİMLERİ YÜKSEKOKULU)0000-0003-2022-2404
Pages
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Publication Date
2026-09-11
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Applications and therapeutic strategies targeting gut microbiota may significantly contribute to preventing NAFLD.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:The estimated prevalence of non-alcoholic fatty liver disease (DD) worldwide is 25%.
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Key Findings & Data:NAFLD is characterized by abnormally increased fat synthesis and subsequent hepatocyte fat accumulation.
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Conclusion & Impact:Applications and therapeutic strategies targeting gut microbiota may significantly contribute to preventing NAFLD.
🔬Design:Review
📍Scope:Comprehensive Sample
⚙️Variables:Metabolic Liver Disease · Microbiota · Non-Alcoholic Fatty Liver Disease

Abstract

The estimated prevalence of non-alcoholic fatty liver disease (DD) worldwide is 25%. The article investigates and evaluates the relationship between NAFLD and gut microbiota and other risk factors, and the role of these factors in the pathogenesis of NAFLD. NAFLD is characterized by abnormally increased fat synthesis and subsequent hepatocyte fat accumulation. Dysbiosis in gut microbiota, disruption of gut flora, overgrowth of bacteria in the gut, disruption of the intestinal barrier, portal transport of bacterial endotoxins to the liver, alteration of bile acid profiles, and reduction of short-chain fatty acids are other factors that play a role in the development of NAFLD. Applications and therapeutic strategies targeting gut microbiota may significantly contribute to preventing NAFLD.

Özet

Alkole bağlı olmayan yağlı karaciğer hastalığı (NAYKH)’nın dünya çapında tahmini yaygınlığı %25’tir. Makalede NAYKH’nın, bağırsak mikrobiyotası ve diğer risk faktörleri ile ilişkisi ve bu faktörlerin NAYKH patogenezinde oynadığı role ilişkin bilgiler araştırılmış ve değerlendirilmiştir. NAYKH, anormal derecede artan yağ sentezi ve bunu takip eden hepatositlerde yağ birikimi ile karakterize bir hastalıktır. Bağırsak mikrobiyotasındaki disbiyoz, bağırsak florasının bozulması, bağırsakta bakterilerin aşırı çoğalması, bağırsak bariyerinin bozulması, bakteriyel endotoksinlerinin karaciğere portal yollar taşınması, safra asidi profillerinin değişmesi ve kısa zincirli yağ asidlerinin azalması, NAYKH gelişmesinde rol oynayan diğer faktörlerdir. NAYKH’nin önlenmesinde, bağırsak mikrobiyotasını hedef alan uygulamalar ve tedavi edici stratejiler önemli katkılar sağlayabilir.

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Cite This Article

Erkmen, O., Karaağaç, R. M. (2026). The Role of Microbiota and Risk Factors in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Current Findings and Therapeutic Strategies. Bilecik Şeyh Edebali Üniversitesi Sağlık Bilimleri Fakültesi Dergisi, Volume: 4 Issue: 3. https://doi.org/10.61535/bseusbfd.1586024

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References (105)

  1. Ali, R., & Cusi, K. (2009). New diagnostic and treatment approaches in non-alcoholic fatty liver disease (NAFLD). Annals of Medicine, 41(4), 265-278. https://doi.org/10.1080/07853890802552437
  2. Alisi, A., Bedogni, G., Baviera, G., Giorgio, V., Porro, E., Paris, C., … Nobili, V. (2014). Randomized clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Alimentary Pharmacology & Therapeutics, 39(11), 1276-1285. https://doi.org/10.1111/apt.12758
  3. Amiri, P., Arefhosseini, S., Bakhshimoghaddam, F., Gurvan, H. J., & Hosseini, S. A. (2022). Mechanistic insights into the pleiotropic effects of butyrate as a potential therapeutic agent on NAFLD management: A systematic review. Frontiers in Nutrition, 9, 1037696. https://doi.org/10.3389/fnut.2022.1037696
  4. Andreasen, A. S., Larsen, N., Pedersen-Skovsgaard, T., Berg, R. M., Møller, K., Svendsen, K. D., … Pedersen, B. K. (2010). Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects. British Journal of Nutrition, 104(12), 1831-1838. https://doi.org/10.1017/S0007114510002874
  5. Araya, J., Rodrigo, R., Videla, L. A., Thielemann, L., Orellana, M., Pettinelli, P., & Poniachik, J. (2004). Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clinical Science, 106, 635–643. https://doi.org/10.1042/CS20030326
  6. Baba, B., Ceylani, T., Gurbanov, R., Acıkgo, E., Keskin, S., Allahverdi, H., … Teker, H. T. (2024). Promoting longevity in aged liver through NLRP3 inflammasome inhibition using tauroursodeoxycholic acid (TUDCA) and SCD probiotics. Archives of Gerontology and Geriatrics, 125, 105517. https://doi.org/10.1016/j.archger.2024.105517
  7. Bajaj, J. S., Heuman, D. M., Hylemon, P. B., Sanyal, A. J., Puri, P., Sterling, R. K… Gillevet, P. M. (2014). Randomized clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Alimentary Pharmacology & Therapeutics, 39(10), 1113-1125. https://doi.org/10.1111/apt.12695
  8. Bajaj, J. S., Idilman, R., Mabudian, L., Hood, M., Fagan, A., Turan, D., … Gillevet, P. M. (2018). Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort. Hepatology, 68(1), 234-247. https://doi.org/10.1002/hep.29791
  9. Bajaj, J. S., Kassam, Z., Fagan, A., Gavis, E. A., Liu, E., Cox, I. J., Kheradman, R., …Gillevet, P. M. (2017). Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology, 66(6), 1727–1738. https://doi.org/10.1002/hep.29306
  10. Banaszak, M., Górna, I., Woźniak, D., Przysławski, J., & Drzymała-Czyż, S. (2023). Association between gut dysbiosis and the occurrence of SIBO, LIBO, SIFO and IMO. Microorganisms, 11(3), 573. https://doi.org/10.3390/microorganisms11030573
  11. Barber, T. M., Kabisch, S., Pfeiffer, A. F. H., & Weickert, M. O. (2023). The effects of the Mediterranean diet on health and gut microbiota. Nutrients, 15(9), 2150. https://doi.org/10.3390/nu15092150
  12. Boursier, J., & Diehl, A. M. (2015). Implication of gut microbiota in non-alcoholic fatty liver disease. PLoS Pathogens, 11(1), e1004559. https://doi.org/10.1371/journal.ppat.1004559
  13. Boursier, J., Mueller, O., Barret, M., Machado, M., Fizanne, L., Araujo-Perez, F., …Diehl, A. M. (2016). The severity of non-alcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology, 63(3), 764-775. https://doi.org/10.1002/hep.28356
  14. Büyüktuncer, Z. (2018). Nutrition, functional foods and microbiota. In: N. Rakıcıoğlu (Ed.), Microbiota, Nutrition and Health (pp. 9-15). Türkiye Klinikleri, Ankara.
  15. Cani, P. D., Possemiers, S., Van de Wiele, T., Guiot, Y., Everard, A., Rottier, O., …Delzenne, N. M. (2009). Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut, 58(8), 1091-1103. https://doi.org/10.1136/gut.2008.165886
  16. Cao, N., Zhao, F., Kwok, L.-Y., Wang, H., & Sun, Z. (2024). Impact of probiotics on weight loss, glucose and lipid metabolism in overweight or obese women: A meta-analysis of randomized controlled trials. Current Research in Food Science, 9, 100810. https://doi.org/10.1016/j.crfs.2024.100810
  17. Chien, C. C., & Chiu, C. H. (2021). Current and future applications of fecal microbiota transplantation for children. Biomedical Journal, 45(1), 11-18. https://doi.org/10.1016/j.bj.2021.11.004
  18. Compare, D., Coccoli, P., Rocco, A., Nardone, O. M., De Maria, S., Cartenì, M., & Nardone, G. (2012). Gut-liver axis: The impact of gut microbiota on non-alcoholic fatty liver disease. Nutrition, Metabolism & Cardiovascular Diseases, 22(6), 471-476. https://doi.org/10.1016/j.numecd.2012.02.007
  19. David, L. A., Mauric, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., …Turnbaugh, P. J. (2014). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505(7484), 559-563. https://doi.org/10.1038/nature12820
  20. Devkota, S., Wang, Y., Musch, M. W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., …Chang, E. B. (2012). Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature, 487(7405), 104-108. https://doi.org/10.1038/nature11225
  21. Dhiman, R. K., Rana, B., Agrawal, S., Garg, A., Chopra, M., Thumburu, K. K., …Chawla, Y. K. (2014). Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: A randomized, controlled trial. Gastroenterology, 147(6), 1327-1337. https://doi.org/10.1053/j.gastro.2014.08.031
  22. Emiroğlu, E., & Güneş, F. E. (2018). Nonalkolik yağlı karaciğer hastalığı ve mikrobiyota. Türkiye Klinikleri Sağlık Bilimleri Dergisi, 3, 254-262.
  23. Endo, H., Niioka, M., Kobayashi, N., Tanaka, M., & Watanabe, T. (2013). Butyrate-producing probiotics reduce non-alcoholic fatty liver disease progression in rats: New insight into the probiotics for the gut-liver axis. PLOS ONE, 8(5), e63388. https://doi.org/10.1371/journal.pone.0063388
  24. Erkmen, O., & Bozoglu, T. F. (2016). Food Microbiology Principles into Practice: Microorganisms Related to Foods, Foodborne Diseases and Food Spoilage (Vol. 1). John Wiley & Sons, Chichester. https://doi.org/10.1002/9781119237860
  25. Forlano, R., Sivakumar, M., Mullish, B. H., & Manousou, P. (2022). Gut microbiota-A future therapeutic target for people with non-alcoholic fatty liver disease: A systematic review. International Journal of Molecular Sciences, 23, 8307. https://doi.org/10.3390/ijms23158307
  26. Gao, R., Meng, X., Xue, Y., Mao, M., Liu, Y., Tian, X., …Zhang, P. (2022). Bile acids-gut microbiota crosstalk contributes to the improvement of type 2 diabetes mellitus. Frontiers in Pharmacology, 13, 1027212. https://doi.org/10.3389/fphar.2022.1027212
  27. Garg, A. (1998). High-monounsaturated-fat diets for patients with diabetes mellitus: A meta-analysis. American Journal of Clinical Nutrition, 67, 577S–582S. https://doi.org/10.1093/ajcn/67.3.577S
  28. Gómez-Pérez, A. M., Ruiz-Limón, P., Salas-Salvadó, J., Vioque, J., Corella, D., Fitó, M., … Tinahones, F. J. (2023). Gut microbiota in nonalcoholic fatty liver disease: A PREDIMED-Plus trial sub analysis. Gut Microbes, 15(1), 2223339. https://doi.org/10.1080/19490976.2023.2223339
  29. Gökcan, H., & Yılmaz, Y. (2023). Alkole bağlı olmayan yağlı karaciğer hastalığı. Türkiye Karaciğer Araştırmaları Derneği. 15 Ocak 2012 tarihinde https://www.tkad.org.tr/wp-content/uploads/2021/09/alkole-bagli-olmayan-yagli-karaciger-hastaliklari.pdf adresinden erişildi.
  30. Guo, M., Li, J., Zhang, L., Chen, C., Wei, Y., & Shen, Z. (2025). Effects of oral supplementation of probiotics on body weight and visceral fat in obese patients: A meta-analysis and systematic review. Scientific Reports, 15, 6355. https://doi.org/10.1038/s41598-025-90820-8
  31. Gurram, B., & Sue, P.K. (2019). Fecal microbiota transplantation in children: Current concepts. Current Opinions in Pediatry, 31, 623-629. https://doi.org/10.1097/MOP.0000000000000787
  32. Hemachandra, S., Rathnayake, S. N., Jayamaha, A. A., Francis, B. S., Welmillage, D., Kaur, D. N., … Abeysekera, M. E. (2025). Fecal microbiota transplantation as an alternative method in the treatment of obesity. Cureus, 17(1), e76858. https://doi.org/10.7759/cureus.76858
  33. Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., …Flavell, R. A. (2012). Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature, 482(7384), 179-185. https://doi.org/10.1038/nature10809
  34. Herman, M. A., & Samuel, V. T. (2016). The sweet path to metabolic demise: Fructose and lipid synthesis. Trends in Endocrinology & Metabolism, 27(10), 719–730. https://doi.org/10.1016/j.tem.2016.06.005
  35. Jegatheesan, P., Beutheu, S., Ventura, G., Sarfati, G., Nubret, E., Kapel, N., …De-Bandt, J. P. (2016). Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease. Clinical Nutrition, 35(1), 175–182. https://doi.org/10.1016/j.clnu.2015.01.021
  36. Jena, P. K., Sheng, L., Liu, H. X., Kalanetra, K. M., Mirsoian, A., Murphy, W. J., …Wan, Y. Y. (2017). Western diet-induced dysbiosis in farnesoid X receptor knockout mice causes persistent hepatic inflammation after antibiotic treatment. American Journal of Pathology, 187(8), 1800-1813. https://doi.org/10.1016/j.ajpath.2017.04.019
  37. Jena, P. K., Sheng, L., Nagar, N., Wu, C., Barile, D., Mill, D. A., & Wan, Y. Y. (2018). The effect of synbiotics Bifidobacterium infantis and milk oligosaccharides on shaping gut microbiota community structure and NASH treatment. Data in Brief, 19, 1025–1029. https://doi.org/10.1016/j.dib.2018.05.127
  38. Kirpich, I. A., Marsano, L. S., & McClain, C. J. (2015). Gut-liver axis, nutrition, and non-alcoholic fatty liver disease. Clinical Biochemistry, 48(13-14), 923-930. https://doi.org/10.1016/j.clinbiochem.2015.06.023
  39. Koning, M., Herrema, H., Nieuwdorp, M., & Meijnikman, A. S. (2023). Targeting nonalcoholic fatty liver disease via gut microbiome-centered therapies. Gut Microbes, 15(1), 2226922. https://doi.org/10.1080/19490976.2023.2226922
  40. Kulkarni, S. R. (2021). Legalities, intellectual property, ethical concerns and regulatory aspects in probiotics. In: S.K. Panda, J. Kellershohn and I. Russesi (Eds.), Probiotic Beverages (pp. 403-424). Elsevier Inc., Chichester. https://doi.org/10.1016/C2018-0-04171-7
  41. Kumar, M., Verma, V., Nagpal, R., Kumar, A., Gautam, S. K., Behare, P. V., … Aggarwal, P. K. (2011). Effect of probiotic fermented milk and chlorophyllin on gene expressions and genotoxicity during AFB1-induced hepatocellular carcinoma. Gene, 490(1-2), 54-59. https://doi.org/10.1016/j.gene.2011.09.003
  42. Lahtinen, P., Juuti, A., Luostarinen, M., Niskanen, L., Liukkonen, T., Tillonen, J., … Arkkila, P. (2022). Effectiveness of fecal microbiota transplantation for weight loss in patients with obesity undergoing bariatric surgery: A randomized clinical trial. JAMA Network Open, 5(12), e2247226. https://doi.org/10.1001/jamanetworkopen.2022.47226
  43. Laue, C., Papazova, E., Pannenbeckers, A., & Schrezenmeir, J. (2023). Effect of a probiotic and a synbiotic on body fat mass, body weight and traits of metabolic syndrome in individuals with abdominal overweight: A randomized controlled clinical study. Nutrients, 15(13), 3039. https://doi.org/10.3390/nu15133039
  44. Leung, C., Rivera, L., Furness, J. B., & Angus, P. W. (2016). The role of the gut microbiota in NAFLD. Nature Reviews Gastroenterology & Hepatology, 13(7), 412-425. https://doi.org/10.1038/nrgastro.2016.85
  45. Lewis, S. J., & Burmeister, S. (2005). A double-blind placebo-controlled study of the effects of Lactobacillus acidophilus on plasma lipids. European Journal of Clinical Nutrition, 59(6), 776-780. https://doi.org/10.1038/sj.ejcn.1602139
  46. Li, X., He, M., Yi, X., Lu, X., Zhu, M., Xue, M.,. Zhu, Y. (2024). Short-chain fatty acids in non-alcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets. Heliyon, 10(5), e26991.
  47. Li, Z., Liu, D., Gu, R., Qiao, Y., Jin, Q., Zhang, Y., …. Jun, W. (2023). Fecal microbiota transplantation in obesity metabolism: A meta analysis and systematic review. Diabetes Research and Clinical Practice, 202, 110803. https://doi.org/10.1016/j.diabres.2023.110803
  48. Liang, Y., Lin, C., Zhang, Y., Deng, Y., Liu, C., & Yang, Q. (2018). Probiotic mixture of Lactobacillus and Bifidobacterium alleviates systemic adiposity and inflammation in non-alcoholic fatty liver disease rats through Gpr109a and the commensal metabolite butyrate. Inflammopharmacology, 26(4), 1051–1055. https://doi.org/10.1007/s10787-018-0479-8
  49. Liu, J., Sun, J., Yu, J., Chen, H., Zhang, D., Zhang, T., … Yu, X. (2023). Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism. NPJ Biofilms and Microbiomes, 9(1). https://doi.org/10.1038/s41522-023-00399-z
  50. Loguercio, C., De Simone, T., Federico, A., Terracciano, F., Tuccillo, C., Di Chicco, M., & Cartenì, M. (2002). Gut-liver axis: A new point of attack to treat chronic liver damage. American Journal of Gastroenterology, 97(8), 2144-2146. https://doi.org/10.1111/j.1572-0241.2002.05942.x
  51. Lu, J., Shataer, D., Yan, H., Dong, X., Zhang, M., Qin, Y., …. Wang, L. (2024). Probiotics and non-alcoholic fatty liver disease: Unveiling the mechanisms of Lactobacillus plantarum and Bifidobacterium bifidum in modulating lipid metabolism, inflammation, and intestinal barrier integrity. Foods, 13(18), 2992. https://doi.org/10.3390/foods13182992
  52. Lunia, M. K., Sharma, B. C., Sharma, P., Sachdeva, S., & Srivastava, S. (2014). Probiotics prevent hepatic encephalopathy in patients with cirrhosis: A randomized controlled trial. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 12(6), 1003-1008. https://doi.org/10.1016/j.cgh.2013.11.006
  53. Ma, J., Zhou, Q., & Li, H. (2017). Gut microbiota and non-alcoholic fatty liver disease: Insights on mechanisms and therapy. Nutrients, 9(10), 1124. https://doi.org/10.3390/nu9101124
  54. Malaguarnera, M., Gargante, M. P., Malaguarnera, G., Salmeri, M., Mastrojeni, S., Rampello, L.,. Galvano, F. (2010). Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. European Journal of Gastroenterology & Hepatology, 22(2), 199-206. https://doi.org/10.1097/MEG.0b013e328330a8d3
  55. Malaguarnera, M., Vacante, M., Antic, T., Giordano, M., Chisari, G., Acquaviva, R., … Galvano, F. (2012). Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Digestive Diseases and Sciences, 57(2), 545–553. https://doi.org/10.1007/s10620-011-1887-4
  56. Mao, T., Zhang, Y., Kaushik, R., & Mohan, M. S. (2024). Effects of polyphenols on gut microbiota and inflammatory markers in individuals with overweight or obesity: A systematic review and meta-analysis of randomized controlled trials. Critical Reviews in Food Science and Nutrition. https://doi.org/10.1080/10408398.2024.2436644
  57. Martin, F.-P., & Kochhar, S. (2015). Introduction to metabonomics in systems biology research. In: S. Kochhar & F.-P. Martin (Eds.), Metabonomics and Gut Microbiota in Nutrition and Disease (pp. 1-24). Springer-Verlag, Berlin.
  58. Matsumoto, K., Ichimura, M., Tsuneyama, K., Moritoki, Y., Tsunashima, H., Omagari, K., … Kikuchi, K. (2017). Fructo-oligosaccharides and intestinal barrier function in a methionine-choline-deficient mouse model of non-alcoholic steatohepatitis. PloS One, 12(6), e0175406. https://doi.org/10.1371/journal.pone.0175406
  59. Mofidi, F., Poustchi, H., Yari, Z., Nourinayyer, B., Merat, S., Sharafkhah, M., … Hekmatdoost, A. (2017). Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: A pilot, randomised, double-blind, placebo-controlled, clinical trial. British Journal of Nutrition, 117(5), 662-668. https://doi.org/10.1017/S0007114517000204
  60. Mollica, M. P., Mattace Raso, G., & Cavaliere, G. (2017). Butyrate regulates liver mitochondrial function, efficiency, and dynamics in insulin-resistant obese mice. Diabetes, 66, 1405–1418.
  61. Nabavi, S., Rafraf, M., Somi, M. H., Homayouni-Rad, A., & Asghari-Jafarabadi, M. (2014). Effects of probiotic yogurt consumption on metabolic factors in individuals with non-alcoholic fatty liver disease. Journal of Dairy Science, 97(12), 7386-7393. https://doi.org/10.3168/jds.2014-8500
  62. Neyrinck, A. M., Possemiers, S., Verstraete, W., De Backer, F., Cani, P. D., & Delzenne, N. M. (2012). Dietary modulation of clostridial cluster XIVa gut bacteria (Roseburia spp.) by chitin-glucan fiber improves host metabolic alterations induced by high-fat diet in mice. Journal of Nutritional Biochemistry, 23(1), 51-59. https://doi.org/10.1016/j.jnutbio.2010.10.008
  63. Niu, X., Zhang, Q., Zhao, Y., Shang, N., Li, S., Liu, Y., …. Wang, R. (2024). Effect of synbiotic supplementation on obesity and gut microbiota in obese adults: A double-blind randomized controlled trial. Frontiers in Nutrition, 11, 1510318. https://doi.org/10.3389/fnut.2024.1510318
  64. O'Keefe, S. J., Li, J. V., Lahti, L., Ou, J., Carbonero, F., Mohammed, K., … Zoetendal, E. G. (2015). Fat, fibre and cancer risk in African American2015s and rural Africans. Nature Communications, 6, 6342. https://doi.org/10.1038/ncomms7342
  65. Pandey, K. R., Naik, S. R., & Vakil, B. V. (2015). Probiotics, prebiotics, and synbiotics-a review. Journal of Food Science and Technology, 52(12), 7577-7587. https://doi.org/10.1007/s13197-015-1921-1
  66. Paniagua, J. A., Gallego de la Sacristana, A., Romero, I., Vidal-Puig, A., Latre, J. M., Sanchez, E., … Perez-Jimenez, F. (2007). Monounsaturated fat-rich diet prevents central body fat distribution and decreases postprandial adiponectin expression induced by a carbohydrate-rich diet in insulin-resistant subjects. Diabetes Care, 30, 1717–1723. https://doi.org/10.2337/dc06-2220
  67. Park, G., Jung, S., Wellen, K. E., & Jang, C. (2021). The interaction between the gut microbiota and dietary carbohydrates in non-alcoholic fatty liver disease. Experimental & Molecular Medicine, 53, 809-822. https://doi.org/10.1038/s12276-021-00614-x
  68. Qiu, B., Liang, J., & Li, C. (2023). Effects of fecal microbiota transplantation in metabolic syndrome: A meta-analysis of randomized controlled trials. PLOS ONE, 18(7), e0288718. https://doi.org/10.1371/journal.pone.0288718
  69. Raman, M., Ahmed, I., Gillevet, P. M., Probert, C. S., Ratcliffe, N. M., Smith, S., … Rioux, K. P. (2013). Fecal microbiome and volatile organic compound metabolome in obese humans with non-alcoholic fatty liver disease. Clinical Gastroenterology and Hepatology, 11(7), 868-875. https://doi.org/10.1016/j.cgh.2013.02.015
  70. Raso, G. M., Simeoli, R., Iacono, A., Santoro, A., Amero, P., Paciello, O… Meli, R. (2014). Effects of a Lactobacillus paracasei B21060-based synbiotic on steatosis, insulin signaling, and toll-like receptor expression in rats fed a high-fat diet. Journal of Nutritional Biochemistry, 25(1), 81-90. https://doi.org/10.1016/j.jnutbio.2013.09.006
  71. Ren, T.-Y., Li, X.-Y., & Fan, F.-G. (2020). Probiotics for treatment of nonalcoholic fatty liver disease: It is worth a try. Clinical Molecular Hepatology, 27(1), 83-86. https://doi.org/10.3350/cmh.2020.0298
  72. Ridlon, J. M., Kang, D. J., Hylemon, P. B., & Bajaj, J. S. (2015). Gut microbiota, cirrhosis, and alcohol regulate bile acid metabolism in the gut. Digestive Diseases, 33(3), 338–345. https://doi.org/10.1159/000371678
  73. Rincon, D., Vaquero, J., Hernando, A., Galindo, E., Ripoll, C., Puerto, M., … Bañares, R. (2014). Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites. Liver International: Official Journal of the International Association for the Study of the Liver, 34(10), 1504-1512. https://doi.org/10.1111/liv.12539
  74. Salminen, S., & Salminen, E. (1997). Lactulose, lactic acid bacteria, intestinal microecology, and mucosal protection. Scandinavian Journal of Gastroenterology, 222, 45-48. https://doi.org/10.1080/00365521.1997.11720717
  75. Sawas, T., Al Halabi, S., Hernaez, R., Carey, W. D., & Cho, W. K. (2015). Patients receiving prebiotics and probiotics before liver transplantation develop fewer infections than controls: A systematic review and meta-analysis. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 13(9), 1567-1574. https://doi.org/10.1016/j.cgh.2015.05.027
  76. Seo, M., Inoue, I., Tanaka, M., Matsuda, N., Nakano, T., Awata, T., … Komoda, T. (2013). Clostridium butyricum MIYAIRI 588 improves high-fat diet-induced non-alcoholic fatty liver disease in rats. Digestive Diseases and Sciences, 58(12), 3534-3544. https://doi.org/10.1007/s10620-013-2879-3
  77. Shen, F., Zheng, R. D., Sun, X. Q., Ding, W. J., Wang, X. Y., & Fan, J. G. (2017). Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease. Hepatobiliary & Pancreatic Diseases International, 16(4), 375-381. https://doi.org/10.1016/S1499-3872(17)60019-5
  78. Shimizu, H., Masujima, Y., Ushiroda, C., Mizushima, R., Taira, S., Ohue-Kitano, R., & Kimura, I. (2019). Dietary short-chain fatty acid intake improves the hepatic metabolic condition via FFAR3. Scientific Reports, 9, 16574. https://doi.org/10.1038/s41598-019-53242-x
  79. Singh, D. P., Khare, P., Zhu, J., Kondepudi, K. K., Singh, J., Baboota, R. K., …Bishnoi, M. (2016). A novel cobiotic-based preventive approach against high-fat diet-induced adiposity, non-alcoholic fatty liver, and gut derangement in mice. International Journal of Obesity, 40(3), 487-496. https://doi.org/10.1038/ijo.2015.197
  80. Solga, S. F., Buckley, G., Clark, J. M., Horska, A., & Diehl, A. M. (2008). The effect of a probiotic on hepatic steatosis. Journal of Clinical Gastroenterology, 42(10), 1117-1119. https://doi.org/10.1097/MCG.0b013e31816d920c
  81. Spadaro, L., Magliocco, O., Spampinato, D., Piro, S., Oliveri, C., Alagona, C., … Purrello, F. (2008). Effects of n-3 polyunsaturated fatty acids in subjects with non-alcoholic fatty liver disease. Digestive and Liver Disease, 40, 194–199. https://doi.org/10.1016/j.dld.2007.10.003
  82. Su, H., Ma, C., Liu, J., Li, N., Gao, M., Huang, A., … Huang, X. (2012). Downregulation of nuclear receptor FXR is associated with multiple malignant clinicopathological characteristics in human hepatocellular carcinoma. American Journal of Gastrointestinal and Liver Physiology, 303(11), G1245-G1253. https://doi.org/10.1152/ajpgi.00439.2011
  83. Sullivan, S. (2010). Implications of diet on non-alcoholic fatty liver disease. Current Opinion in Gastroenterology, 26(2), 160–164. https://doi.org/10.1097/MOG.0b013e3283358a58
  84. Sun, C., Qiu, C., Zhang, Y., Yan, M., Tan, J., He, J., … Wu, L. (2023). Lactiplantibacillus plantarum NKK20 alleviates high-fat-diet-induced non-alcoholic fatty liver disease in mice through regulating bile acid anabolism. Molecules, 28, 4042. https://doi.org/10.3390/molecules28104042
  85. Tarantino, G., & Finelli, C. (2015). Systematic review on intervention with prebiotics/probiotics in patients with obesity-related non-alcoholic fatty liver disease. Future Microbiology, 10(5), 889-902. https://doi.org/10.2217/fmb.15.13
  86. Teker, H. T., Ceylani, T., Keskin, S., Samgane, G., Baba, B., Acıkgoz, E., Gurbanov, R. (2023). Reduced liver damage and fibrosis with combined SCD probiotics and intermittent fasting in aged rat. Journal of Cellular and Molecular Medicine, 28(1). https://doi.org/10.1111/jcmm.18014
  87. Teker, H. T., Ceylani, T., Keskin, S., Samgane, G., Baba, B., Acıkgoz, E., & Gurbanov, R (2024). Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats. Journal of Cellular and Molecular Medicine, 28(6), e18203. https://doi.org/10.1111/jcmm.18203
  88. Vajro, P., Mandato, C., Licenziati, M. R., Franzese, A., Vitale, D. F., Lenta, S., …Meli, R. (2011). Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. Journal of Pediatric Gastroenterology and Nutrition, 52(6), 740-743. https://doi.org/10.1097/MPG.0b013e31821f9b85
  89. Walters, W. A., Xu, Z., & Knight, R. (2014). Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Letters, 588(22), 4223-4233. https://doi.org/10.1016/j.febslet.2014.09.039
  90. Wang, L., & Wan, Y. Y. (2019). The role of gut microbiota in liver disease development and treatment. Liver Research, 3(1), 3-18. https://doi.org/10.1016/j.livres.2019.02.001
  91. Wang, W. W., Zhang, Y., Huang, X. B., You, N., Zheng, L., & Li, J. (2017). Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction. World Journal of Gastroenterology, 23(38), 6983-6994. https://doi.org/10.3748/wjg.v23.i38.6983
  92. WGO (2023). Probiotics and prebiotics (Global Guidelines). World Gastroenterology Organization (WGO). 21 Mayıs 2024 tarihinde https://www.worldgastroenterology.org/UserFiles/file/guidelines/probiotics-and-prebiotics-english-2023.pdf adresinden erişildi.
  93. Xu, X., Zhang, F., Ren, J., Zhang, H., Jing, C., Wei, M., … Xie, H. (2024). Dietary intervention improves metabolic levels in patients with type 2 diabetes through the gut microbiota: A systematic review and meta-analysis. Frontiers in Nutrition, 10. https://doi.org/10.3389/fnut.2023.1243095
  94. Xue, L., Deng, Z., Luo, W., He, X., & Chen, Y. (2022). Effect of fecal microbiota transplantation on non-alcoholic fatty liver disease: A clinical trial. Frontiers in Cellular and Infection Microbiology, 12, 759306.
  95. Xue, L., He, J., Gao, N., Lu, X., Li, M., Wu, X., … Geng, Y. (2017). Probiotics may delay the progression of non-alcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia. Scientific Reports, 7, 45176. https://doi.org/10.1038/srep45176
  96. Yang, C., Xu, J., Xu, X., Xu, W., Tong, B., Wang, S., … Zhu, Y. (2023). Characteristics of gut microbiota in patients with metabolic associated fatty liver disease. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-023-37163-4
  97. Yang, J., Fu, X., Liao, X., & Li, Y. (2020). Effects of gut microbial-based treatments on gut microbiota, behavioral symptoms, and gastrointestinal symptoms in children with autism spectrum disorder: A systematic review. Psychiatric Research, 293, 113471. https://doi.org/10.1016/j.psychres.2020.113471.
  98. Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Dominguez-Bello, M. G., Contreras, M., … Gordon, J. I. (2012). Human gut microbiome viewed across age and geography. Nature, 486(7402), 222-227. https://doi.org/10.1038/nature11053
  99. Zhang, Z., Mocanu, V., Cai, C., Dang, J., Slater, L., Deehan, E. C., … Madsen, K. L. (2019). Impact of fecal microbiota transplantation on obesity and metabolic syndrome-a systematic review. Nutrients, 11(10), 2291. https://doi.org/10.3390/nu11102291
  100. Zhao, H., Gao, X., Liu, Z., Zhang, L., Fang, X., Sun, J., … Sun, Y. (2022). Sodium alginate prevents non-alcoholic fatty liver disease by modulating the gut–liver axis in high-fat diet-fed rats. Nutrients, 14, 4846. https://doi.org/10.3390/nu14224846
  101. Zhou, D., Pan, Q., Xin, F. Z., Zhang, R. N., He, C. X., Chen, G. Y., … Fan, J. G. (2017). Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier. World Journal of Gastroenterology, 23(1), 60–75. https://doi.org/10.3748/wjg.v23.i1.60
  102. Zhou, X,, Wang, J,, Zhou, S,, Liao, J,, Ye, Z,, & Mao, L. (2023). Efficacy of probiotics on nonalcoholic fatty liver disease: A meta-analysis. Medicine, 102(4), e32734. https://doi.org/10.1097/MD.0000000000032734
  103. Zhu, W., Yan, M., Cao, H., Zhou, J., & Xu, Z. (2022). Effects of Clostridium butyricum capsules combined with rosuvastatin on intestinal flora, lipid metabolism, liver function and inflammation in NAFLD patients. Cellular and Molecular Biology, 68, 64–69. https://doi.org/10.14715/cmb/2022.68.2.10
  104. Li, X., He, M., Yi, X., Lu, X., Zhu, M., Xue, M.,. Zhu, Y. (2024). Short-chain fatty acids in non-alcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets. Heliyon, 10(5), e26991.
  105. Malaguarnera, M., Gargante, M. P., Malaguarnera, G., Salmeri, M., Mastrojeni, S., Rampello, L.,. Galvano, F. (2010). Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy. European Journal of Gastroenterology & Hepatology, 22(2), 199-206. https://doi.org/10.1097/MEG.0b013e328330a8d3