IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.
Glucagon-like peptide-1 (GLP-1) is a hormone secreted from enteroendocrine cells that can promote weight loss and blood glucose improvement. We screened probiotic strains that effectively stimulate GLP-1 secretion from human enteroendocrine cells and then investigated the efficacy of this strain in a high-fat diet (HFD)-induced mouse model of obesity. Lactiplantibacillus plantarum GB104 greatly induced GLP-1 secretion by increasing expression of the proglucagon gene (GCG), but not the proprotein convertase subtilisin/kexin type 1 gene (PCSK1) in the human enteroendocrine cell line NCI-H716. In an HFD-induced mouse model of obesity, GB104 inhibited weight gain and improved blood glucose levels by increasing blood GLP-1 levels. It also tended to attenuate the HFD-induced changes in blood levels of other hormones and suppressed fat accumulation in the liver and adipose tissues. In white adipose tissue, GB104 suppressed inflammation by reducing pro-inflammatory M1 macrophages and increasing anti-inflammatory M2 macrophages and regulatory T cells. Probiotic strains that promote GLP-1 secretion, such as GB104, may serve as a promising candidate for dietary intervention against obesity and metabolic diseases.
Given the recognized involvement of the gut microbiome in the development of obesity, considerable efforts are being made to discover probiotics capable of preventing and managing obesity. In this study, we report the discovery of Lactiplantibacillus plantarum GBCC_F0227, isolated from fermented food, which exhibited superior triglyceride catabolism efficacy compared to L. plantarum WCSF1. Molecular analysis showed elevated expression levels of α/β hydrolases with lipase activity (abH04, abH08_1, abH08_2, abH11_1, and abH11_2) in L. plantarum GBCC_F0227 compared to L. plantarum WCFS1, demonstrating its enhanced lipolytic activity. In a high-fat-diet (HFD)-induced mouse obesity model, the administration of L. plantarum GBCC_F0227 mitigated weight gain, reduced blood triglycerides, and diminished fat mass. Furthermore, L. plantarum GBCC_F0227 upregulated adiponectin gene expression in adipose tissue, indicative of favorable metabolic modulation, and showed robust growth and low cytotoxicity, underscoring its industrial viability. Therefore, our findings encourage the further investigation of L. plantarum GBCC_F0227’s therapeutic applications for the prevention and treatment of obesity and associated metabolic diseases.