Imunobiótico Lactobacillus delbrueckii CIDCA 133: explorando seu efeito bioterapêutico na colite ulcerativa

Abstract

Lactobacillus delbrueckii subsp. lactis CIDCA 133 has long been recognized for its immunoregulatory properties. The benefits of this bacterium, including a fermented milk formulation, have been extensively reported in a murine model of chemotherapy-induced intestinal mucositis. Interestingly, these outcomes have been maintained even after the bacterium’s heat inactivation, demonstrating that this strain’s postbiotic form can also promote beneficial effects. Despite these properties, the immunobiotic activity of CIDCA 133 in other models of inflammation, such as inflammatory bowel disease (IBD), remains unexplored. In addition, the specific bacterial components responsible for the beneficial effects of CIDCA 133 are still unknown. In this context, this Thesis aimed to evaluate the biotherapeutic functionality of CIDCA 133 in ulcerative colitis through a fermented milk formulation and to investigate whether proteins extracted from CIDCA 133 are responsible, at least in part, for the anti-inflammatory effects of the strain. The main results demonstrated high levels of acetate produced in milk fermented by CIDCA 133, and that the administration of the immunobiotic formulation attenuates ulcerative colitis by reducing the expression of inflammatory markers (MPO, NAG, sIgA, Nfkb1, Tlr2, Tnf, Il6 and Il10), and modulating the gut dysbiosis, mainly regulating the abundance of Bacteroides, Lactobacillus and Helicobacter genus. CIDCA 133 fermented milk also improved epithelial barrier function by reducing intestinal permeability, increasing the expression of tight junction proteins (Hp and F11r), and modulating the expression of short-chain fatty acid-activated receptors such as GPR43 and GPR109. Interestingly, these beneficial effects were also observed after administration of proteins extracted from CIDCA 133. These postbiotic components reduced the cellular inflammatory infiltrate (neutrophils and macrophages) and the gene expression of inflammatory markers in the colon (Tlr2, Nfkb1, Nlpr3, Tnf, and Il6). Consumption of CIDCA 133 proteins also improved epithelial barrier function and modulated the profile of cytokines such as IFNγ, IL17a, IL1β, TGFβ and IL10. Additionally, this postbiotic proteins fraction regulated the gut microbiota, evidenced by the increased abundance of the genus Akkermansia and Oscillospira, and the reduced abundance of Bacteroides and Dorea. Overall, the promising results indicate that L. delbrueckii CIDCA 133 plays an immunobiotic function in ulcerative colitis, and that proteins extracted from this strain are important molecules contributing, at least in part, to the observed anti-inflammatory effects.