Milk Fat Globule Membrane Alleviated Intestinal Barrier Dysfunction In Rats After Massive Small Bowel Resection

Backgrounds & Aims: The milk fat globule membrane(MFGM)contains various bioactive components which have been shown to inhibit pathogen colonization and maintain gut barrier integrity.The aim of the present study was to evaluate the protective effects of MFGM on intestinal barrier integrity and function and the possible mechanism through the NLRP3 inflammasome pathway in a rat model of short bowel syndrome.Methods: Twenty-four male Sprague-Dawley(SD)rats were randomly divided into three groups(n = 8 per group).Groups consisted of rats subjected to bowel transection and reanastomosis(Sham)and rats submitted to massive small bowel resection then supplemented with either water(SBS)or 1.5g/kg.day MFGM(SBS+MFGM)by daily gavage.Body weight was measured every day,and rats were sacrificed on day 15 post-operation.Intestinal adaptation was evaluated by assessing ileum morphological and histological changes.Intestinal permeability was determined by serum fluorescein isothiocyanate-dextran-40,000 daltons(FD-40)and bacterial translocation(BT).Expression of tight junction proteins and the inflammasome NLRP3-ASC-caspase-1 pathway in the ileum were measured by western-blotting.Concentrations of inflammatory cytokines(IL-1?,IL-18)in the ileum and sIgA levels of ileum content were measured by ELISA.Results: Sham operated animals had higher body weight than SBS and SBS+MFGM groups,and the latter two groups showed similar results in body weight,villus height and crypt depth of ileum.Intestinal permeability and BT rate were increased in the SBS group(1.73(1.21,1.97)?g/ml,87.5%)as compared with Sham(0.07(0.05,0.10)?g/ml,37.5%)and SBS+MFGM(0.29(0.21,0.64)?g/ml,25%)groups(P < 0.05),which was accompanied by decreased expression of the tight junction proteins and different distribution in ileum.The ileum tissue of SBS rats showed higher IL-1? levels than Sham and SBS+MFGM group(P < 0.05),and IL-18 levels in ileum tissue were significantly lower in SBS group compared with Sham and SBS+MFGM groups(P < 0.05).Supplementation with MFGM also resulted in a significantly higher sIgA concentration in ileum contents than those in SBS and Sham groups.SBS rats had significantly higher expressions of NLRP3,ASC,caspase-1 in ileum tissues,with no difference detected between Sham and SBS+MFGM group.Conclusions: Enteral supplementation of MFGM help to maintain intestinal barrier integrity & function and reduce NLRP3 inflammasome activation in SBS.Overall,these observations support a role for MFGM in gut health and provide experimental support for applications in intestinal failure although further clinical and mechanistic studies are needed.