Gut microbiota as a potential predictor of therapeutic response in adults with Crohn’s disease: A systematic review

Abstract

BACKGROUND

Various therapeutic options are available for the treatment of Crohn’s disease (CD). About 30%-40% patients experience primary non-response, and 20%-30% secondary loss of response to biological therapy. Predicting therapeutic response is challenging and an area of active research. Gut microbiota has emerged as an important player in the pathogenesis of CD and also appears to be a promising biomarker for predicting therapeutic response.

AIM

To systematically review the literature on the current status of gut microbiota as a tool to predict response to treatment in adults with CD.

METHODS

We searched the literature database (PubMed, Scopus, and Cochrane database) from inception to August 2025. We screened for studies reporting on adult patients with CD receiving biologic or immunomodulator therapies, with baseline microbiome analyses performed prior to treatment. Papers reporting on baseline gut microbiota as a predictor of therapeutic response were finally included. The utility of bacterial diversity, microbial community structure, and the role of specific operational taxonomic units as biomarkers of therapeutic response was reviewed. The results were grouped based on the bacterial parameters studied and presented in separate tables. The quality of the included studies was assessed using the MINORS criteria. The review was registered prospectively in PROSPERO.

RESULTS

After applying the selection criteria, sixteen studies were included in this systematic review. The majority of the papers were from Europe and the United States. All except two papers assessed gut bacterial population using 16S rRNA gene sequencing. Ten of the sixteen studies were of high quality. Among the sixteen studies included, most identified an association between microbial taxa and treatment response, while the relation with alpha-diversity was inconsistent. The functional characteristics were reported in only four studies and were found to be useful. The best prediction was achieved when microbial characteristics were combined with clinical and other parameters, with area under the curve values up to 0.96.

CONCLUSION

The overall results suggest good performance of microbial parameters as a novel biomarker of therapeutic response. However, there are variations across individual studies, probably related to the methodology of assessing microbial communities and the therapeutic agent used. Future multicenter studies integrating microbial, clinical, and metabolomic data are warranted to develop predictive models for personalized therapy in CD.

Keywords: Gut microbiota; Crohn’s disease; Therapy; Predictor; Diversity; Bacteria

Core Tip: Crohn’s disease is a chronic inflammatory bowel condition requiring lifelong therapy. However, about one-third of patients do not respond to any particular treatment, and a change of therapy is needed. There is a need for identifying predictors of therapy before treatment to avoid non-response, but such markers are uncommon. Accumulating evidence suggests that the gut bacterial population can serve as a potentially useful prediction tool. In this review, we have presented the current status of the role of gut microbial community as a biomarker of response. The results are encouraging but further work is needed before they can be used in clinical practice.