The Apparent Asymmetrical Relationship Between Small Bowel Bacterial Overgrowth, Endotoxemia, and Liver Steatosis and Fibrosis in Cirrhotic and Non-Cirrhotic Patients: A Single-Center Pilot Study

Abstract

IntroductionGut microbiota are a complex ecosystem harboring our intestine. They maintain human body equilibrium, while their derangement, namely, “dysbiosis“, has been associated with several gastrointestinal diseases, such as liver steatosis (NAFLD) and liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) is an example of dysbiosis of the upper gastrointestinal (GI) tract.AimThe aim of this study is to evaluate the relationship between SIBO and levels of endotoxemia and grade of liver steatosis (LS) and liver fibrosis (LF) in hepatologic patients.Materials and MethodsConsecutive outpatients referred to our hepatology clinic were tested for SIBO by the lactulose breath test (LBT) and peripheral blood levels of endotoxemia; LS grading and LF were assessed by abdominal ultrasound and transient elastography, respectively.ResultsFifty-two consecutive patients (17 with alcohol abuse (4.5 ± 0.8 alcohol units per day), 4 with HCV and 2 with HBV infection, 24 of metabolic origin, 2 of autoimmune origin, and 3 with cholangiopathies; mean age 54.7 ± 8.3 years, 31 F, BMI 24.1 ± 1.1 Kg/m2) and 14 healthy volunteers (HV) (mean age 50.1 ± 4.3 years, 9 F, BMI 23.3 ± 1.1 Kg/m2) were enrolled. SIBO prevalence was significantly higher in cirrhotic (LC) vs. non-cirrhotic (LNC) patients and vs. HV (all, p < 0.05), with a significant positive trend according to Child-Pugh status (all, p < 0.05). SIBO prevalence was not correlated with LS stages (all, p = NS). Consensually, endotoxin levels were significantly higher in LC vs. LNC and vs. HV (all, p < 0.05) and significantly correlated with LF in patients with LC, according to Child-Pugh status (all, p < 0.05).ConclusionThis study shows that SIBO prevalence and relative endotoxin blood levels seem to be significantly associated with the grade of LF vs. LS in LC. SIBO is also present under pre-cirrhotic conditions, but its prevalence seems to correlate with liver disease irreversible derangement.

Prevalence of Small Intestinal Bacterial Overgrowth Syndrome in Patients with Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis: A Cross-Sectional Study

“…Moreover, in their study of 35 liver biopsy-proven NAFLD patients, Miele et al concluded that the prevalence of SIBO increased significantly with the severity of steatosis ( p = 0.001), without a significant correlation between SIBO and the presence of NASH ( p = 0.84) [ 40 ]. Similar to our results, in a study by Scarpellini et al, a higher prevalence of SIBO, diagnosed using the lactulose breath test, was observed in patients with cirrhosis compared with non-cirrhotic patients (41.2% vs. 13.1%; p < 0.05), but no association was observed between SIBO prevalence and the grade of liver steatosis, as diagnosed using abdominal ultrasound [ 38 ]. On the other hand, a study by Shi et al reported that as the severity of steatosis, expressed as the controlled attenuation parameter, increased, the prevalence of SIBO also increased, ranging from 32.6% to 88% for mild and severe steatosis, respectively [ 35 ].…”

“…Interestingly, in two of the studies that used the 10 5 cfu/mL threshold after jejunal aspirate culture to diagnose SIBO, the prevalence of SIBO was reported to be 37.5% and 47.2% [ 33 , 34 ]. Finally, it is worth mentioning that the prevalence of SIBO in the control group was similar to those reported in the literature in studies performed either in the field of NAFLD [ 38 ] or other diseases [ 39 ].…”

“…Our study showed that the prevalence of SIBO among patients with NASH-associated cirrhosis was significantly higher compared with patients with NAFL. The relationship between SIBO prevalence and disease stage has been the focus of many studies in this field [ 33 , 34 , 35 , 38 , 40 , 41 , 42 ], with inconclusive results. One of the first studies, that included 136 patients with available liver biopsy who underwent a glucose hydrogen breath test for SIBO detection, demonstrated that SIBO was more frequent among patients with non-severe hepatic steatosis (26.3% vs. 10.3%, p = 0.127), whereas it did not differ in patients with NASH [ 41 ].…”

“…Accumulating evidence from published studies suggests a multifactorial contribution of SIBO in the development and progression of NAFLD [ 17 , 18 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The main proposed mechanisms include a disturbance of energy homeostasis leading to energy salvage, increased oxidative stress, enhancement of insulin resistance, increased ethanol production, and alterations in the metabolism of choline and bile acids [ 18 , 31 , 46 ].…”

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“…Mutlu et al [ 68 ] demonstrated that alcohol consumption can cause small intestinal bacterial overgrowth (SIBO). Both aerobic and anaerobic bacteria are increased in subjects with chronic alcohol intake and alcoholic cirrhosis compared to healthy controls [ 69 ]. SIBO and intestinal dysbiosis have also been observed in animal models with alcoholic liver disease [ 69 , 70 ].…”