Long-term unbalanced diet might lead to intestinal malodorous gas generation and inflammation, which would cause health problems, especially in confined environment. In this study, the effects of high-fat and high-protein diets from different nutrient sources, including casein lard, soy protein and soybean oil, and pork protein and lard, respectively, on the differences of malodorous gas compounds emission and inflammation in rats were explored as well as the correlation with gut microbiota. The results showed that all the high-fat and high-protein diets could induce organ damage, abnormal serum biochemical indexes and inflammation. However, the malodorous gas compounds in the three experimental groups were totally different, which might be because the production of malodorous gas compounds was jointly regulated by the intestinal microbiota and liver cytochrome P450.