Targeted delivery of short-chain fatty acid butyrate to the lower gastrointestinal tract by polymeric nanoscale micelles restores intestinal homeostasis in a mouse model of peanut allergy and colitis.
Normal intestinal homeostasis protects the host against external stimuli including pathogens, food antigens and toxins in the intestinal lumen.1, Maintenance of intestinal homeostasis depends on cooperation of the commensal microbiome, the epithelial barrier and the host immune system2,3, Therefore, intestinal dysfunction inevitably leads to mucosal and systemic diseases, such as food allergy, asthma and inflammatory bowel disease.4,5,6, Conventional therapeutics do not provide many of the necessary regulatory effects, and may even reduce the integrity of the epithelial barrier and cause intestinal microbial imbalance and excessive immunosuppression. Oral probiotics, transplants of fecal microbiota, and other therapies have recently shown beneficial results in preclinical studies.7,8, However, a growing body of conflicting clinical results suggests that the bioavailability of probiotic formulations is poor and their efficacy limited. And, despite improvements in treatment efficacy, transplantation of fecal microbiota is associated with increased risk of serious infections and reduced patient compliance. Nevertheless, gut microbial metabolites, especially short-chain fatty acids, have been shown to be effective in the regulation of intestinal homeostasis.9,10, But orally administered short-chain fatty acids are absorbed by the small intestine and metabolized too rapidly to be able to maintain a therapeutic effect. writing now Nature Biomedical EngineeringKatherine Nagler, Jeffrey Hubbell and colleagues1 1 report that in mouse models of peanut allergy and colitis, a combination of neutral and negatively charged polymeric nanoscale micelles can deliver butyrate – a short-chain fatty acid produced by gut microbes when breaking down dietary fiber – to the gastrointestinal (GI) ) in areas of the tract and restore intestinal homeostasis. Locally released butyrate strengthens the epithelial barrier, increasing the abundance of butyrate-producing clostridium and suppressed immune activation.