Etiology-Specific Patterns of Small Intestinal Bacterial and Methanogen Overgrowth in Chronic Liver Disease

Abstract

Background/Aim: The gut–liver axis is increasingly recognized as an important contributor to chronic liver disease progression, but the distribution of small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO) across different liver disease etiologies remains insufficiently defined. Metabolic liver disease and viral hepatitis represent biologically distinct conditions with different inflammatory, metabolic, cholestatic and fibrosis-related profiles. This study aimed to compare the prevalence of SIBO and IMO between patients with metabolic liver disease and viral hepatitis and to evaluate accompanying clinical and biochemical differences in a pooled cohort.
Methods: Two clinical datasets were merged and de-identified. The final analysis included 311 patients with chronic liver disease: 133 with metabolic liver disease and 178 with viral hepatitis. SIBO and IMO status were standardized from breath-test-based variables. Demographic characteristics, liver enzymes, platelet count, hemoglobin, erythrocyte sedimentation rate, ultrasonographic findings and FIB-4 index were analyzed. Continuous variables were expressed as median with interquartile range and compared using the Mann–Whitney U test. Categorical variables were compared using chi-square or Fisher’s exact test. Odds ratios with 95% confidence intervals were calculated for major categorical outcomes.
Results: SIBO status was available in 310 patients, and 109 were SIBO-positive, corresponding to an overall prevalence of 35.2%. SIBO was detected in 40/133 patients with metabolic liver disease and 69/177 patients with viral hepatitis (Figure 1). The prevalence was therefore 30.1% in the metabolic group and 39.0% in the viral hepatitis group. Although SIBO was numerically more frequent among viral hepatitis patients, this difference did not reach statistical significance (p=0.104; OR 1.49, 95% CI 0.92–2.40). In contrast, IMO showed a clearly different etiological distribution. IMO was significantly more common in metabolic liver disease than in viral hepatitis, being detected in 22/81 versus 8/78 evaluable patients, respectively (27.2% vs 10.3%, p=0.006; OR 3.26, 95% CI 1.35–7.87) (Figure 2). Compared with viral hepatitis, metabolic liver disease patients had higher ALT, GGT, platelet count and hemoglobin levels, while viral hepatitis patients had higher ALP, ESR and FIB-4 values. These findings suggest that bacterial and methanogen overgrowth may reflect different biological patterns in chronic liver disease, with SIBO being relatively more frequent in viral etiologies and IMO being more strongly linked to metabolic liver disease.
Conclusion: In this pooled cohort of 311 patients, more than one-third had SIBO, confirming that microbial overgrowth is common in chronic liver disease. SIBO prevalence was numerically higher in viral hepatitis, whereas IMO was significantly associated with metabolic liver disease. These results support the concept that SIBO and IMO should be evaluated as distinct gut microbial phenotypes rather than a single entity. Larger prospective studies with multivariable adjustment are needed to clarify whether these patterns are independently related to liver disease etiology, metabolic dysfunction, fibrosis burden, symptoms or treatment outcomes.