Abstract
Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease with a rising global incidence. Existing therapies are often limited by suboptimal efficacy and frequent relapse. Gut microbiota dysbiosis is central to UC pathogenesis, providing a rationale for probiotic-based, microbiota-targeted interventions. This review synthesizes evidence that probiotics mitigate UC through multiple synergistic mechanisms: competitive exclusion to rebalance the microbiota, upregulation of tight junction proteins to restore the intestinal barrier, and bidirectional immunomodulation to restrain excessive inflammation. These mechanisms are supported by extensive preclinical and clinical data. Research is increasingly moving beyond conventional live formulations toward defined postbiotics, probiotic-traditional Chinese medicine combinations, targeted delivery systems engineered with smart materials, and fecal microbiota transplantation. These strategies seek to overcome limitations such as low bacterial viability and poor targeting, thereby improving therapeutic precision and efficacy. Collectively, probiotics and their derivative approaches offer promising adjunct or alternative options for the clinical management of UC via multitarget modulation of the intestinal microenvironment.