Understanding the gut microbiota to shape the future of intestinal failure care: a systematic review of the evidence.

Intestinal failure (IF) patients suffer a loss of intestinal mass or function and alterations in gut microbiota (GM) composition and function. Our objectives are to (1) characterise GM in IF, (2) explore associations between GM and IF health outcomes, and (3) analyse the effect of GM-based interventions on disease course. A systematic review was conducted in PubMed/MEDLINE, Embase, and Web of Science up to March 2026. Eligible studies included observational studies, prospective studies, and clinical trials in patients with IF, without age or date restrictions. The main outcomes identified included GM diversity indices, GM taxonomy, and IF complications. Risk of bias was assessed using CASP checklists. Twenty-eight studies including children (4 case reports, 1 case series, 19 cohort studies [14 cross-sectional, 5 prospective], 1 quasi-experimental study, 3 RCTs, for a total of 391 cases) and 19 studies including adults (2 case reports, 1 case series, 14 cohort studies [12 cross-sectional, 2 prospective], 2 quasi-experimental studies, for a total of 604 cases) were analysed. Given the heterogeneity among studies, only qualitative synthesis was performed. Reduced alpha diversity and marked phylum-level dysbiosis are consistently reported in patients with IF compared with healthy controls. Different IF aetiologies and bowel anatomy are associated with distinctive GM patterns. IF complication rate increases with the magnitude of GM alteration. GM-modifying interventions are poorly studied. Encouraging improvements in GM dysbiosis, enteral tolerance, and IF complications have been reported in observational studies using various interventions. Still, these findings are not confirmed in RCTs. A distinguishing GM dysbiosis, associated with worse clinical outcomes, clearly emerges in patients with IF. The low quality and heterogeneity of the studies analysed limit data interpretation. The need for a better definition of microbiota assessment, both as a bedside tool and as a therapeutic target, is highlighted as a prominent study topic for the future of IF rehabilitation. What is Known: • Intestinal failure yields substantial alterations in gut microbiota habitat, leading to dysbiosis. • The severity of dysbiosis influences multiple clinically relevant health outcomes. What is New: • IF aetiology, short bowel subtype, and patient age influence GM alterations in IF patients. • Limited longitudinal data suggest that some adverse outcomes are a result of specific dysbiosis pattern progression. • Therapies targeting GM are promising tools for personalised intestinal rehabilitation.