Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles

Abstract

The microbiome modulates host immunity and aids the maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Yet modern dietary factors and the excessive use of antibiotics have contributed to the rising incidence of food allergies, inflammatory bowel disease and other non-communicable chronic diseases associated with the depletion of beneficial taxa, including butyrate-producing Clostridia. Here we show that intragastrically delivered neutral and negatively charged polymeric micelles releasing butyrate in different regions of the intestinal tract restore barrier-protective responses in mouse models of colitis and of peanut allergy. Treatment with the butyrate-releasing micelles increased the abundance of butyrate-producing taxa in Clostridium cluster XIVa, protected mice from an anaphylactic reaction to a peanut challenge and reduced disease severity in a T-cell-transfer model of colitis. By restoring microbial and mucosal homoeostasis, butyrate-releasing micelles may function as an antigen-agnostic approach for the treatment of allergic and inflammatory diseases.

Adoptive T reg therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome

“…T cell metabolic programming holds promise to extend cell therapy by adjusting or maintaining the cell functions. Reported strategies such as fatty acid–releasing particles or direct fatty acid supplements to restore the mucosal homeostasis highlighted the vital role of short-chain fatty acid in T reg cells ( 15 , 32 , 46 , 47 ). Metabolism could also affect the survival of cancer cells (Warburg effect) and the persistence of cytotoxic T cells, suggesting the potential of metabolic treatment in cancer immunotherapy ( 48 , 49 ).…”

In vitro assessment of the effect of four polysaccharides on intestinal bacteria of mice with colitis

“…Propionate could lower fatty acid content in the liver and plasma, reduces food intake, exerts immunosuppressive actions, and probably improves tissue insulin sensitivity (Sa'ad et al., 2010). Butyrate is a crucial energy source for intestinal epithelial cells and plays a critical role in maintaining the integrity of the intestinal mucosal barrier and stabilizing the intestinal microenvironment (Furusawa et al., 2013; Wang et al., 2023). This study found that after fermentation by the gut microbiota, pectin and guar gum produced higher levels of acetate and butyrate, whereas guar gum also produced more propionate.…”

Glycosylation-modified antigens as a tolerance-inducing vaccine platform prevent anaphylaxis in a pre-clinical model of food allergy

“…Dysbiotic mouse models, including antibiotic-treated and gnotobiotic mice, have been used to gain insight and develop potential therapeutics for food allergies [26][27][28] . Here, we used a dysbiotic mouse model to investigate the prophylactic efficacy of BLG (Figure 2A).…”