More than 60% of domestic cats in the United States are either overweight or obese (OW). High-protein low-carbohydrate (HPLC) diets have been recommended for weight management for humans and pets. Gut microbes can influence the host's health and metabolism. Less is known about feline gut microbiomes compared to other species. Thirty-nine lean (LN) and OW domestic short-haired cats (median age, 7.2 years) with median body fat of 15.8 and 32.5%, respectively, were enrolled in a two-phase study. All cats were fed the control diet (CON) with 32.4% protein and 32.3% carbohydrate for 8 weeks followed by another 8 weeks of intervention where half of the cats continued the CON diet while the other half were switched to a HPLC diet with 51.4% protein and 11.6% carbohydrate. The goal was to understand how the HPLC diet influenced gut microbiota in obese vs. lean cats. The 16S rRNA gene profiling study revealed a significant impact on gut microbiome by dietary protein and carbohydrate ratio. The effect was more pronounced in OW cats than LN cats. While no microbial taxon was different between groups in LN cats, compositional changes occurred at different taxonomical ranks in OW cats. At the phylum level, Fusobacteria became more abundant in HPLC-fed cats than in CON-fed cats. At the genus level, five short-chain fatty acid (SCFA) producers had altered compositions in response to the diets: Faecalibacterium and Fusobacterium are more abundant in HPLC-fed cats while the abundances of Megasphaera, Bifidobacterium, and Veillonella increased in CON-fed cats. Predicted microbial gene networks showed changes in energy metabolism and one-carbon metabolism pathways. Our study demonstrated differential responses to HPLC diet between obese vs. lean cats and opportunities to explore these SCFA-producers for weight management in cats.