Dysbiosis-Associated Mortality During Dextran Sulfate Sodium (DSS) Induced Murine Colitis is Reduced by 2’-fucosyllactose, a Human Milk Oligosaccharide

The mouse DSS model of IBD exhibits many similarities with human ulcerative colitis. Our model uses antibiotic-induced dysbiosis to increase sensitivity to DSS damage. Human milk oligosaccharides (HMOSs) and a principal component, 2’-fucosyllactose (2'-FL), protect the vulnerable neonatal gut through inhibition of pathogen binding, prebiotic activity, and direct inhibition of inflammation. The ability of 2’-FL to ameliorate DSS damage was tested in dysbiotic mice. 12-week old male C57BL/6 mice, following a 14 day course of antibiotics (kanamycin, gentamicin, colistin, metronidazole, and vancomycin), were treated for 7 days with 3.5% DSS with or without 2'-FL. After 3 days recovery, animals were sacrificed. The antibiotic treatment caused dysbiosis of gut microbiota. The most dysbiotic (lowest colony number) were most sensitive to DSS, exhibiting exacerbated body weight loss, bleeding, proinflammatory cytokines, and invasive pathobionts in their liver, kidney and lung. In these mice, 2’-FL decreased body weight loss, disease activity index scores, and increased survival. This protection by 2’-FL is associated with decreased pathobiont colonization in colon and invasion to organs, and reduced IL-17 levels. Amelioration of colitis by HMOS is consistent with lower risk of inflammatory diseases in breastfed infants, and suggests utility for 2’-FL in treating clinical inflammatory diseases.