Work

Postoperative inulin supplementation is associated with microbiota remodeling and improved colonic anastomotic healing in LPS-primed mice

Year: 2026

Type: article

Abstract: Background Anastomotic leakage is a major colorectal surgical complication that may be exacerbated by perioperative inflammatory stress. How transcriptomic profiles and tissue-adherent microbiota change under such stress, and whether postoperative inulin supplementation is associated with microbiota changes and improved healing after inflammatory priming, remain unclear. Methods Two independent animal experiments were conducted. Experiment 1 compared control (CON) and LPS-primed mice using scheduled, repeated-cross-sectional sampling for microbiota profiling on POD0, 1, 3, 5, 7, and 14 and for RNA-seq on POD0, 1, 3, 5, and 7. Experiment 2 used the same murine colonic anastomosis model to evaluate postoperative exclusive enteral nutrition (EEN) with or without inulin supplementation (dietary fiber, DF) in a 2 × 2 factorial design comprising CON, CON-DF, LPS, and LPS-DF groups. Healing was assessed by survival, recovery scores, anastomotic burst pressure, histology, immunostaining, and short-chain-fatty-acid quantification. Within Experiment 2, a dedicated n = 10/group survival/longitudinal cohort was followed through POD5, and a separate terminal cohort provided six surviving mice/group for POD5 assessments; five microscopy fields were averaged within each mouse. Results LPS priming impaired healing and induced niche-specific microbiota alterations with altered bacterial microspatial patterns at the suture line. DF supplementation was associated with improved recovery and anastomotic strength, reduced inflammatory infiltration, increased proliferation, decreased apoptosis, and altered inflammatory- and repair-associated immune markers. The planned LPS-DF versus LPS survival comparison in the POD5 four-group cohort was not significant after multiplicity correction. At POD5, DF was associated with lower Shannon diversity and an altered short-chain-fatty-acid profile, including higher acetate; the LPS × inulin interactions for these measures were not significant. Conclusion Brief postoperative inulin-supplemented EEN improved anastomotic healing following inflammatory priming, concurrent with microbiota remodeling and short-chain-fatty-acid differences, including higher acetate. These concurrent changes do not establish microbiota- or SCFA-mediated causality.

Source: Frontiers in Microbiology

DOI: 10.3389/fmicb.2026.1895439