Milk Fat Globule Membrane Enhances Colonic–Mucus‐Barrier Function in a Rat Model of Short‐Bowel Syndrome

Abstract Background Clinical research reveals that colon plays an important role in mitigating the effects of short‐bowel syndrome (SBS). Previously, we showed that the milk fat globule membrane (MFGM) had protective effects on gut barrier integrity in the rat SBS model. Here, we used the same rat model to investigate the effects of enteral MFGM supplementation on gut microbiota and colonic–mucus‐barrier function and its related mechanisms. Methods We randomly divided 24 male Sprague‐Dawley rats into 3 groups: Sham, SBS (rats with massive small‐bowel resection), and SBS+MFGM (SBS rats supplemented with 1.5 g/kg/d MFGM). We then evaluated gut permeability, crypt depth, goblet‐cell count, mucin 1 (MUC1), mucin 2 (MUC2), microbiota, short‐chain fatty acids, and protein expressions of nucleotide‐binding oligomerization domain, leucine‐rich repeat, and pyrin domain‐containing protein 6 (NLRP6) pathway of the colon. Results Compared with SBS rats, SBS+MFGM rats exhibited lower intestinal permeability, increased crypt depth, more goblet cells, and more MUC1/MUC2‐positive cells. The SBS+MFGM group also had greater Firmicutes abundance and lower acetate concentration ( P < .05). Sham rats had significantly lower Bacteroidetes abundance than SBS rats, but SBS+MFGM and SBS groups did not differ. Additionally, the SBS+MFGM group had higher NLRP6 and interleukin (IL)‐18 expression but lower IL‐1β and Caspase‐1 (cysteinyl aspartate‐specific protease‐1) expression than the SBS group ( P < .05). Conclusion Supplementation of MFGM modulates gut microbiota composition in SBS, possibly through strengthening the colonic mucus barrier and regulation of NLRP6 inflammasome.