[Butyrate alleviates Clostridium difficile infection in high-fat diet-induced obese mice]

To investigate the mechanism by which obesity exacerbates Clostridium difficile infection (CDI) and explore the value of gut microbiota metabolite butyrate as an alternative therapy.

In mouse models of high-fat diet (HFD)-induced obesity and CDI and normal diet-fed mouse models of CDI, the effect of butyrate treatment on hepatic lipid deposition and liver function was assessed using Oil Red O staining and by measuring aspartate aminotransferase and alanine aminotransferase levels. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) of the mice were determined, and colonic injury was evaluated using HE staining. The expression levels of intestinal mucosal barrier proteins ZO-1 and occludin were detected by RT-PCR and immunohistochemistry, and the levels of C. difficile toxins A and B in mouse serum and feces were measured using RT-PCR and ELISA. The concentration of short-chain fatty acids (SCFAs) in mouse feces was determined using gas chromatography-mass spectrometry. In HCT116 cells induced by palmitic acid in the presence or absence of C. difficile, the effect of butyrate expression levels of ZO-1 and occludin were examined by immunofluorescence staining, and cell apoptosis was analyzed with flow cytometry.

Compared with normal diet-fed mice, the HFD-fed mice with CDI had a significantly higher mortality rate and exhibited severer colonic damage, intestinal barrier function impairment and liver injury with significantly reduced fecal SCFAs concentrations. Butyrate replacement therapy markedly alleviated CDI symptoms, improved intestinal barrier function, and reduced the levels of liver injury markers. Fecal microbiota transplantation produced similar effects to butyrate and obviously alleviated CDI symptoms and increased fecal SCFAs concentrations in the mouse models.

HFD significantly exacerbates the progression of CDI in mice, and butyrate shows the potential as an alternative therapy for improving obesity-associated CDI.