Six-Week High-Fat Diet Alters the Gut Microbiome and Promotes Cecal Inflammation, Endotoxin Production, and Simple Steatosis without Obesity in Male Rats

Energy-dense foods can alter gut microbial diversity. However, the physiological effects of diet-induced microbial changes on the development of nonalcoholic fatty liver disease (NAFLD) remain debatable. We hypothesized that high-fat intake for 6 weeks would promote intestinal dysbiosis by increasing gram-positive bacteria, inducing the intestinal production of proinflammatory cytokines and subsequent hepatic lipid infiltration in young male rats. Six-week old male Sprague–Dawley rats were divided into two groups and fed either a standard rodent chow or a 60% high-fat diet (HFD) for 6 weeks. Chromogenic endotoxin quantification assays indicate an increase in lipopolysaccharide concentration in the plasma of HFD rats (p = 0.032). Additionally, Western blot analyses of the cecum showed significantly greater protein expression of the transcription factor, nuclear factor kappa B (NF-kB), (p = 0.037) and the proinflammatory cytokine, interleukin-1β (IL-1β), (p = 0.042) in rats fed HFD. Linear discriminate analysis of effect size (LEfSe) showed greater abundance of Firmicutes and Actinobacteria in the samples collected from the cecum of HFD rats compared to chow. Consistent with the development of steatosis, the Oil-Red-O-stained area was increased in liver sections from HFD rats. Hepatic triacylglycerol concentrations (p < 0.001) and plasma alanine aminotransferase (p < 0.001) were significantly increased in HFD-fed animals compared to chow. These findings show that a short duration of high-fat consumption can have profound deleterious effects on gastrointestinal health and the inflammatory state of these young male Sprague–Dawley rats.