Sergiy Tkach, Olena Gubska, Tetiana Cheverda


Background. Emerging evidence suggests a strong interaction between the gut, gut microbiota and liver. Derangement of gut flora, particularly small intestinal bacterial overgrowth (SIBO), occurs in a large percentage of patients with non-alcoholic fatty liver disease (NAFLD) and plays an important role in its pathogenesis.

Aim. Study of the frequency of SIBO in various forms of non-alcoholic fatty liver disease, as well as the possibilities of its pathomorphosis as a result of eradication of SIBO as a result of the use of rifaximin or multicomponent probiotic.

Material and methods. There were investigated 125 patients with non-alcoholic fatty liver disease (70 men, 55 women aged 18 to 65 years, mean age 37±6.7 years) developed at obesity or type 2 diabetes mellitus, including 85 patients with liver steatosis (group1) and 40 patients with non-alcoholic steatohepatitis (group 2). Patients with concomitant SIBO (70 patients) was treated with rifaximin or multicomponent probiotic. As the main endpoints of the study, the frequency of achieving eradication of SIBO was evaluated (estimated from the results of a repeated H2-lactulose hydrogen test after treatment), as well as a decrease in the severity of liver steatosis by steatometry and a decrease / normalization of transaminase levels 3 months after the start of the treatment. Secondary endpoints included the change in BMI and the HOMA-IR index 3 months after the start of the treatment.

Results. SIBO in patients with non-alcoholic fatty liver disease was significantly more frequent than in control (p <0.005), and in patients with non-alcoholic steatohepatitis – significantly more often than in patients with liver steatosis (80 % vs 47.1 %, P <0.01). Eradication of SIBO after use of rifaximin was recorded in 30 of 36 patients with non-alcoholic fatty liver disease (83.3 %), including 16 of 20 patients with steatosis (80 %) and 14 of 16 (87.5 %) patients with non-alcoholic steatohepatitis. In the group of patients taking multicomponent probiotics after treatment, eradication of SIBO was noted in 12 of 36 patients (33.3 %), including 7 patients with steatosis (35 %) and 5 patients (31.3 %) with non-alcoholic steatohepatitis

Conclusion. The investigation shows that the eradication of small intestinal bacterial overgrowth has the positive influence on the natural course of NAFLD and use of rifaximine should be discussed as a perspective therapeutic strategy at this pathology


non-alcoholic fatty liver disease; syndrome of bacterial owergrowth; prophylaxis and treatment; rifaximin

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Williams, C. D., Stengel, J., Asike, M. I., Torres, D. M., Shaw, J., Contreras, M. et. al. (2011). Prevalence of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among a Largely Middle-Aged Population Utilizing Ultrasound and Liver Biopsy: A Prospective Study. Gastroenterology, 140 (1), 124–131. doi: 10.1053/j.gastro.2010.09.038

Law, K., Brunt, E. M. (2010). Nonalcoholic Fatty Liver Disease. Clinics in Liver Disease, 14 (4), 591–604. doi: 10.1016/j.cld.2010.07.006

Nagata, K., Suzuki, H., Sakaguchi, S. (2007). Common pathogenic mechanism in development progression of liver injury caused by non-alcoholic or alcoholic steatohepatitis. The Journal of Toxicological Sciences, 32 (5), 453–468. doi: 10.2131/jts.32.453

Tilg, H., Moschen, A. R. (2010). Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology, 52 (5), 1836–1846. doi: 10.1002/hep.24001

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 and Cardiovascular Diseases, 22 (6), 471–476. doi: 10.1016/j.numecd.2012.02.007

Vanni, E., Bugianesi, E. (2009). The gut-liver axis in nonalcoholic fatty liver disease: Another pathway to insulin resistance? Hepatology, 49 (6), 1790–1792. doi: 10.1002/hep.23036

Blanco, C., Loguercio, C., Machado, M. V., Cortez-Pinto, H. (2012). Gut microbiota and nonalcoholic fatty liver disease. Annals of Hepatology, 11 (4), 440–449.

Shanab, A. A., Scully, P., Crosbie, O., Buckley, M., O’Mahony, L., Shanahan, F. et. al. (2010). Small Intestinal Bacterial Overgrowth in Nonalcoholic Steatohepatitis: Association with Toll-Like Receptor 4 Expression and Plasma Levels of Interleukin 8. Digestive Diseases and Sciences, 56 (5), 1524–1534. doi: 10.1007/s10620-010-1447-3

Abu-Shanab, A., Quigley, E. M. M. (2010). The role of the gut microbiota in nonalcoholic fatty liver disease. Nature Reviews Gastroenterology & Hepatology, 7 (12), 691–701. doi: 10.1038/nrgastro.2010.172

Sabate, J.-M., Jouet, P., Harnois, F., Mechler, C., Msika, S., Grossin, M., Coffin, B. (2008). High Prevalence of Small Intestinal Bacterial Overgrowth in Patients with Morbid Obesity: A Contributor to Severe Hepatic Steatosis. Obesity Surgery, 18 (4), 371–377. doi: 10.1007/s11695-007-9398-2

Giannelli, V., Di Gregorio, V., Iebba, V., Giusto, M., Schippa, S., Merli, M., Thalheimer, U. (2014). Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis. World Journal of Gastroenterology, 20 (45), 16795–16810. doi: 10.3748/wjg.v20.i45.16795

Buss, C., Valle-Tovo, C., Miozzo, S., Alves de Mattos, A. (2014). Probiotics and synbiotics may improve liver aminotransferases levels in non-alcoholic fatty liver disease patients. Annals of hepatology, 13 (5), 482–488.

Parnell, J. A., Raman, M., Rioux, K. P., Reimer, R. A. (2011). The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance. Liver International, 32 (5), 701–711. doi: 10.1111/j.1478-3231.2011.02730.x

Pappo, I., Bercovier, H., Berry, E. M., Haviv, Y., Gallily, R., Freund, H. R. (1992). Polymyxin B Reduces Total Parenteral Nutrition-Associated Hepatic Steatosis by Its Antibacterial Activity and by Blocking Deleterious Effects of Lipopolysaccharide. Journal of Parenteral and Enteral Nutrition, 16 (6), 529–532. doi: 10.1177/0148607192016006529

Koo, H. L., DuPont, H. L. (2010). Rifaximin: a unique gastrointestinal-selective antibiotic for enteric diseases. Current Opinion in Gastroenterology, 26 (1), 17–25. doi: 10.1097/mog.0b013e328333dc8d

Gao, J., Gillilland, M., Owyang, C. (2014). Rifaximin, gut microbes and mucosal inflammation: unraveling a complex relationship. Gut Microbes, 5 (4), 571–575. doi: 10.4161/gmic.32130

Musso, G., Gambino, R., Cassader, M., Pagano, G. (2010). A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology, 52 (1), 79–104. doi: 10.1002/hep.23623

Velayudham, A., Dolganiuc, A., Ellis, M., Petrasek, J., Kodys, K., Mandrekar, P., Szabo, G. (2008). VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology, 49 (3), 989–997. doi: 10.1002/hep.22711

Javadi, L., Ghavami, M., Khoshbaten, M., Safaiyan, A., Barzegari, A., Gargari, B. P. (2017). The potential role of probiotics or/and prebiotic on serum lipid profile and insulin resistance in alcoholic fatty liver disease: A double blind randomized clinical trial. Crescent Journal of Medical and Biological Sciences, 4 (3), 131–138.

Lambert, J. E., Parnell, J. A., Eksteen, B., Raman, M., Bomhof, M. R., Rioux, K. P. et. al. (2015). Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol. BMC Gastroenterology, 15 (1), 169. doi: 10.1186/s12876-015-0400-5

Ma, X., Hua, J., Li, Z. (2008). Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. Journal of Hepatology, 49 (5), 821–830. doi: 10.1016/j.jhep.2008.05.025

Malaguarnera, M., Vacante, M., Antic, T., Giordano, M., Chisari, G., Acquaviva, R. et. al. (2011). Bifidobacterium longum with Fructo-Oligosaccharides in Patients with Non Alcoholic Steatohepatitis. Digestive Diseases and Sciences, 57 (2), 545–553. doi: 10.1007/s10620-011-1887-4



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