Underlying MASLD-induced gut microbiome dysbiosis and intestinal inflammation are key to poor outcomes in vibriosis infections in a preclinical model

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease globally, especially in developed countries, including the United States. The etiology of MASLD is closely associated with several other cardiometabolic conditions and can further aggravate to more severe stages of liver disease, including steatohepatitis and cirrhosis. Moreover, patients with underlying MASLD conditions have altered gut microbiome signatures and intestinal homeostasis, leading to gut barrier dysfunction, thereby making them more vulnerable to acute gastrointestinal infections like non-cholera vibriosis. However, the exact role of the gut microbiome and intestinal pathophysiology in increasing susceptibility to infection in patients with MASLD remains poorly understood. In this study, we used oral inoculation of the bacterium Vibrio vulnificus to investigate the pathophysiological outcomes in both control and diet-induced MASLD mouse cohorts. Our results showed that non-cholera vibriosis in mice with underlying MASLD caused increased liver damage, an inflammatory surge, followed by the onset of fibrotic lesions compared to the chow-diet fed control mice, depicting a worsened outcome. Depletion of the gut bacteriome by antibiotic treatment and following fecal microbiota transplantation in these mouse cohorts showed decreased pathophysiology in the livers, indicating that an altered gut microbiome in MASLD could be a key factor in the increased likelihood of non-cholera vibriosis in patients with MASLD.