Effects of Milk Polar Lipids on Colitis Are Dependent on Dietary Fat Content

OBJECTIVES: In North America, over 1.5 million people suffer from inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Changes in environmental and lifestyle factors coinciding with westernization has driven a rapid acceleration in IBD prevalence worldwide. The objectives of this study were to identify how different milk lipids affect colitis disease activity, the colonic transcriptome, and the microbiome in a mouse model of chemical-induced colitis. METHODS: Male and female C57BL6/J mice (n = 120) were randomized into either a low (5% w/w) milk fat (LFD) or high (21% w/w) milk fat diet (HFD) supplemented with either 0%, 1%, or 2% w/w of milk polar lipids (MPLs) for 3 weeks (n = 10/group/sex). Afterwards, colitis was induced using 1% dextran sodium sulfate (DSS) in drinking water for 5 days and regular drinking water was given for the final 5 days. Colons were used for histology, transcriptomics by RNA-sequencing, and real-time qRT-PCR, and cecal feces were collected for 16S rRNA sequencing for microbiome analysis. Disease Activity Index (DAI) was recorded daily consisting of a weight loss, bleeding, and stool consistency score. RESULTS: MPLs attenuated DAI score in HFD compared to control during the colitis induction and recovery phase, while MPLs in LFD exacerbated DAI during the recovery period. Colon transcriptomics showed that males fed HFD with MPLs had lower expression of genes associated with inflammatory signaling compared to the HFD without MPLs. Colons of the males fed LFD with MPLs had upregulated pathways involved in inflammatory cytokines and antimicrobial activity and downregulated pathways involved in cAMP signaling and extracellular matrix constituents. Fecal Verrucomicrobia was the most abundant bacterial phyla, while MPLs increased Proteobacteria and Bacteroidetes in LFD compared to HFD in males. Male mice had higher microbial diversity and MPLs increased alpha diversity measures. CONCLUSIONS: MPLs protected against colitis in mice fed HFD but promoted the disease under LFD conditions. These results suggest the influence of MPLs on colitis is dependent on dietary fat content. FUNDING SOURCES: This research was supported by a USDA NIFA AFRI grant to C. Blesso.