Prophylactic treatment of Lacticaseibacillus paracasei K56 ameliorates asthma by regulating short-chain fatty acid production and Treg differentiation

Many studies have shown that the development of allergic asthma is associated with intestinal microbiota dysbiosis. Based on the gut-lung axis theory, probiotic intervention may be a potential strategy for respiratory diseases. Lacticaseibacillus paracasei K56 was reported to regulate gut microbiota in mice. However, its effect on allergic asthma has not been reported. In this study, we investigated the effect of the K56 on ovalbumininduced asthma and its possible mechanisms. Our results showed that K56 reduced asthma symptoms and inflammatory cell infiltration in the lung of asthmatic mice. And K56 regulated the differentiation of helper T cells in the lung and intestine. Results from 16S rRNA gene sequencing showed that K56 prophylaxis significantly elevated the richness of Akkermansia and Burkholderia. Meanwhile, K56 abrogated the decrease in the levels of short-chain fatty acids (SCFAs) in the feces. In addition, a rebound in the mRNA expression of the SCFA receptors was observed after K56 prophylaxis. Notably, the regulatory T cell (Treg) frequencies and the FFAR3 levels were positively correlated. These results suggest that K56 could attenuate asthma, possibly by modulating the intestinal microbiota and regulating Treg differentiation through SCFA metabolized. Our study showed that K56 may be used as a probiotic to prevent pulmonary inflammation and dysbiosis of the intestinal microbiota in allergic asthma. (c) 2025 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).