Biomarkers of Probiotic Therapy in Ulcerative Colitis: A Systematic Review of Mechanisms Underlying Remission

Ulcerative colitis (UC) is a chronic immune-mediated inflammatory bowel disease of unknown aetiology that affects the colon. Patients with UC typically exhibit dysbiosis - an altered gut microbiota profile compared with healthy individuals, who have a more diverse microbial community - suggesting that dysbiosis may be either a cause or a consequence of UC. Current therapeutics include aminosalicylates and steroids with anti-inflammatory and immunosuppressive properties; however, these treatments do not address dysbiosis and instead relieve symptoms. Antibiotics are sometimes used to exert selective pressure on the microbiota and eliminate Gram-negative bacteria, but they are associated with significant side effects, including diarrhoea, Clostridioides difficile infection, thrush, and peripheral neuropathy. Probiotics, live microorganisms that confer a health benefit on the host, represent a growing area of interest in the treatment of inflammatory bowel disease (IBD), with the potential to modulate the gut microbiota. Randomised controlled trials (RCTs) measuring biomarkers in patients with UC treated with probiotics were identified through searches of four databases. After screening against predefined inclusion and exclusion criteria, eligible studies were assessed for risk of bias. Thirteen RCTs were included, using interventions such as VSL#3 (Actial Nutrition Inc., Covington, Louisiana) and bifidobacteria-fermented milk (BFM), and measured biomarkers including cytokines over follow-up periods of up to one year. Pro-inflammatory signalling markers, such as nuclear factor-κB (NF-κB), were measured in two of 13 studies and showed significant reductions following probiotic therapy. Conversely, anti-inflammatory biomarkers such as interleukin-10 (IL-10) were significantly increased in all four studies that assessed them. These findings provide insights into the inflammatory pathways targeted by probiotics, including down-regulation of Toll-like receptor 2 (TLR2), leading to reduced pro-inflammatory cytokine production. Such results may inform the development of novel therapeutics targeting these pathways and support the use of biomarkers as objective indicators of disease activity or treatment response, in contrast to potentially biased clinical scores.