Alterations in the gut microbiome and intestinal barrier associated with metabolic dysfunction–associated steatotic liver disease (MASLD) may contribute to more severe outcomes in non-cholera vibriosis, according to a recent preclinical study.
MASLD is the most common chronic liver disease worldwide and is associated with metabolic comorbidities and increased susceptibility to infection. Previous studies have shown that patients with chronic liver disease are at higher risk of infection with Vibrio vulnificus, a foodborne pathogen linked to severe gastroenteritis and septicemia. However, the biological mechanisms underlying this increased risk have remained unclear.
In this study, researchers used a diet-induced mouse model of MASLD and exposed animals to V. vulnificus via oral inoculation. Compared with control mice, those with MASLD developed more severe liver injury following infection. Findings included higher levels of liver enzymes, increased inflammation, and evidence of fibrotic changes.
Histologic and immunohistochemical analyses supported these observations, showing increased expression of inflammatory and fibrotic markers in the livers of MASLD mice after infection. These changes are consistent with more advanced liver injury and tissue remodeling.
The investigators also identified significant disruption of intestinal barrier function in MASLD mice. Expression of tight junction proteins was reduced after infection, while markers of gut permeability and endotoxemia were increased. In parallel, markers of intestinal and systemic inflammation, including interleukin-1β and immunoglobulin A, were elevated.
Analysis of the gut microbiome showed differences in microbial composition between MASLD and control animals. MASLD mice had reduced levels of bacteria associated with gut health and increased levels of organisms linked to mucus degradation and inflammation. The study also identified a higher diversity of antibiotic resistance genes in the MASLD group.
To test whether these microbiome changes contributed to disease severity, the researchers depleted the gut microbiota with antibiotics and then performed fecal microbiota transplantation (FMT). Mice with MASLD that received a “healthy” microbiome showed reduced liver injury, lower inflammatory markers, and improved histologic findings after infection.
Overall, the findings suggest that gut microbiome disruption and impaired intestinal barrier function may play a role in the severity of Vibrio infections in MASLD. For pathologists and laboratory professionals, the study highlights potential relevance of inflammatory markers, gut barrier integrity, and microbiome-related changes when assessing infection risk in patients with underlying liver disease.
The authors note that the findings are based on an acute mouse model and that further studies are needed to determine how these mechanisms apply to human disease.
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