The impact of probiotics and microbiome-targeted therapy on Crohn’s disease improvement: A systematic review

Abstract Crohn’s disease (CD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract in which intestinal dysbiosis plays a central pathogenic role. Microbiome-directed therapies—including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT)—have emerged as potential adjuncts to conventional treatment. However, evidence on their clinical efficacy and microbiome effects remains inconsistent. To evaluate the impact of microbiome-targeted therapies on clinical outcomes, inflammatory markers, and gut microbial composition in patients with Crohn’s disease. A systematic review with qualitative synthesis was conducted according to PRISMA guidelines. PubMed, Embase, Scopus, and Cochrane Library were searched to identify studies involving patients with CD receiving probiotics, prebiotics, synbiotics, mesalamine–probiotic combinations, or FMT. The data extracted included study and population characteristics, remission rates, disease activity indices, endoscopic response, inflammatory biomarkers, microbiome alterations, and adverse events. The review protocol was registered in PROSPERO (CRD420251012069). Five studies met the inclusion criteria. FMT did not significantly improve combined clinical and endoscopic remission compared with placebo; however, reductions in CRP, ESR, fecal calprotectin, and PCDAI were observed within treatment groups. The studies involving probiotics and synbiotics demonstrated reductions in CDAI or PCDAI scores, improved mucosal integrity, and modulation of inflammatory cytokines (↓TNF-α, ↑IL-10). In contrast, the prebiotic did not achieve significant clinical remission compared to placebo, it only resulted in a measurable increase in the target Bifidobacterium species. Microbiome analyses indicated partial restoration of beneficial taxa such as Faecalibacterium , Roseburia , and Bifidobacterium . No serious treatment-related adverse events were reported, although one prebiotic trial noted a significantly higher withdrawal rate due to gastrointestinal discomfort. Microbiome-targeted therapies exert measurable anti-inflammatory and microbiota-modulating effects in Crohn’s disease, although consistent clinical and endoscopic remission remains limited. These interventions show biological activity but evidence remains insufficient to support routine clinical use. The lack of serious adverse effects in most interventions may support their use in combination with standard therapy. Larger, standardized trials are needed to establish efficacy and long-term outcomes.