Immunomodulatory Effects of Lactococcus lactis on the Gut—Pancreas Axis 2257747

Abstract Introduction Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic beta cells by T lymphocytes, resulting in insulin deficiency. Our group has shown unique alterations in the gut mucosa and microbiome dysbiosis in pre-diabetic mice that occur prior to insulin deficiency in Non-Obese Diabetic (NOD) mice. These findings suggest that the gut microbiome may influence the gut mucosa and modulate disease progression. Lymph node sharing between the intestine and the pancreas may play a critical role in determining disease onset. This study investigated the immunomodulatory effects of Lactococcus lactis NCDO 2118 supplementation on 4 weeks female NOD mice treated for 28 days. Methods Major gut microbiota phyla were analyzed by qPCR of fecal DNA, and short-chain fatty acids were determined by liquid chromatography. Secretory IgA (SIgA) was quantified by ELISA, and IgA-bound bacteria (Bac-IgA) and cell populations were analyzed by flow cytometry. Results L. lactis administration significantly reduced (p = 0.0095) the frequency and severity of pancreatic insulitis, without affecting food or water intake, blood glucose, body weight, intestine size, or SIgA levels. Bac-IgA levels were decreased in treated mice. Innate Lymphoid Cells, Intraepithelial and T lymphocytes profiles were unchanged in the gut, while B cells and plasmocytes were decreased in the Peyer’s patches of treated mice. L. lactis-treated mice displayed a lower proportion of tolerogenic dendritic cells in the spleen and gut-pancreas shared lymph nodes. An increase in total bacteria and Firmicutes, and a reduction in Proteobacteria, were observed in the colon of the treated group, along with higher levels of acetate and lactate. Conclusion In conclusion, L. lactis NCDO 2118 reduced insulitis in NOD mice and promoted an immunomodulatory profile during T1DM development, likely mediated by alterations in the gut microbiota and the gut—pancreas axis. Funding Source CNPq, CAPES and FAPEMIG (#RED-00096-22, #RED-00067-23) Topic Categories Mucosal and Regional Immunology (MUC)