Probiotics are increasingly used to manage gut dysbiosis-related conditions due to their robust ability to manipulate the gut microbial community. However, few studies have reported that probiotics can specifically modulate individual gut microbes. This study demonstrated that administering the probiotic, Lactiplantibacillus fermentum F6, could ameliorate dextran sulfate sodium-induced colitis in a rat model, evidenced by the decreases in the disease activity index score, histopathology grading, and serum pro-inflammatory cytokine levels, as well as the increase in the serum anti-inflammatory cytokine levels. Shotgun metagenomics revealed that the fecal metagenomic of colitis rats receiving the probiotic intervention contained substantially fewer Akkermansia muciniphila than the dextran sulfate sodium group. Thus, the probiotic mechanism might be exerted by reducing specific gut microbial species associated with disease pathogenesis. A new paradigm for designing probiotics that manage diseases through direct and precise manipulation of gut microbes has been provided through this study.