Morphological and permeability changes of the intestine in patients nourished exclusively with parenteral nutrition: a systematic review and meta-analysis

While evidence from animal models suggests that total parenteral nutrition (TPN) induces alterations in the intestinal mucosa, effects on humans are not clearly established. To analyse alterations in morphology and permeability associated with TPN in human intestinal mucosa, we conducted a systematic review following PRISMA recommendations. MEDLINE and Embase databases were searched from inception to May 2025 for literature on adults receiving TPN for any condition irrespective of the nutritional comparator. Outcome measures were intestinal morphological and permeability assessments. Meta-analyses conducted to synthesise the evidence were based on the random effects model because of heterogeneity in design characteristics. Of 1071 studies identified, 20 were included (morphology:10, and permeability: 13). Synthesis showed no significant short-term changes in villus height, crypt depth, or mucosal thickness over time after TPN. Villus height (mean difference: -87.51 µm [95%CI: -106.56, -68.46]) and crypt depth (mean difference: -44.48 µm [95%CI: -77.62, -11.34]) were significantly lower in patients on TPN compared to healthy volunteers or patients with dyspepsia. The lactulose/mannitol (L/M) ratios were significantly increased during TPN compared to baseline values (mean difference: 0.04 [95%CI: 0.02, 0.07]), and were also significantly higher for TPN compared to the enteral diet (mean difference: 0.03 [95%CI: 0.02, 0.05]). The overall strength of the evidence was low to moderate. Clinical status may have influenced the inconsistencies found in morphological outcomes. A possible association between altered permeability and TPN was observed; however, surgery and inflammation may have also contributed. The clinical significance of these findings and the effects of TPN duration and composition remain unclear. Prospero registration number CRD42022265814.