Probiotics of Lacticaseibacillus paracasei SD1 and Lacticaseibacillus rhamnosus SD11 attenuate inflammation and β-cell death in streptozotocin-induced type 1 diabetic mice

Abstract

Probiotics provide health benefits in various aspects and are believed to modulate the immune system by balancing gut microbiota homeostasis, termed the “microbiota-immune axis”. Recent evidence supports that several Lactobacillus strains possess glucose-lowering and anti-inflammatory effects in an animal model of type 1 diabetes (T1D). Although probiotics of Lacticaseibacillus paracasei SD1 (SD1) and Lacticaseibacillus rhamnosus SD11 (SD11) exert human oral health benefits by reducing harmful bacterial populations, their clinical application regarding hypoglycemic-related traits as well as the underlying mechanisms are still lacking. In this report, we used multiple low doses of streptozotocin (STZ)-induced diabetic BALB/c mice to explore the effects of SD1 and SD11 supplementation on the regulation of markers related to T1D. Experimental mice were randomly assigned into five groups, non-STZ + V, STZ + V, STZ + SD1, STZ + SD11, and STZ + SDM (mixture of SD1 and SD11), and physiological data were measured every week. Blood and pancreas samples were collected at 4- and 8-weeks. Our results indicate that supplementation with SD1, SD11, or SDM for 8 weeks significantly improved body weights, glycemic levels, glucose tolerance, insulin levels, and lipid profiles. Probiotic administration also preserved islet integrity and increased β-cell mass in STZ-injected mice, as well as prevented infiltration of macrophages, CD4+, and CD8+ T cells into the islets. Significantly, SD1 and SD11 suppressed the levels of IL1-β, TNF-α and IFN-γ and increased IL-10, which is concomitant with the inhibition of cleaved caspase 3, caspase 9, caspase 8, proapoptotic Bax, NF-κBp65, pSTAT1, and iNOS. Additionally, the survival ability of β-cells was mediated by upregulated anti-apoptotic Bcl2. We conclude that SD1 and SD11 attenuate STZ-induced diabetic mice by stabilizing glycemic levels and reducing inflammation, thereby protecting β-cells. Among the probiotic treatment groups, SD11 revealed the best results in almost all parameters, indicating its potential use for alleviating hyperglycemia-associated symptoms.

Natural Sweetener Glycyrrhetinic Acid Monoglucuronide Improves Glucose Homeostasis in Healthy Mice

“…But sucralose reduced the level of isobutyric acid and butyric acid in colon contents, and aspartame reduced the level of butyric acid, which may be caused by the sucralose- or aspartame-altered gut microbiota. For example, sucralose decreased Lactobacillus, which could promote the production of SCFAs, and aspartame increased Ruminococcus, which was related with low levels of SCFAs. , Intake of inulin, grain fiber, and cymbidium polysaccharide can increase SCFAs by increasing SCFA-producing bacteria, relieve symptoms of type 2 diabetes, and improve insulin sensitivity. , Previous findings have shown that SCFAs have beneficial effects on blood glucose control, insulin resistance reduction, and inflammation relief. ,, For example, the ingestion of butyrate, propionate, or acetate all protected against diet-induced obesity and insulin resistance, which may be because SCFAs participate in energy metabolism . Remarkably, some studies demonstrated that SCFAs produced by bacterial fermentation in the gut can directly influence L cells to enhance the release of peptides such as GLP-1 and PYY, proving the important role of the SCFAs in GLP-1 and PYY release.…”

“…27 Moreover, Lactobacillus abundance decreased and Adlercreutzia abundance increased in the sucralose group. Lactobacillus as beneficial bacteria can alleviate inflammation and plays a positive role in antioxidant and glucose-lowering effects, 28 whereas Adlercreutzia abundance is associated with obesity and insulin resistance in rodents. 29 LEfSe analysis showed that Odoribacter, Ruminiclostridium, and Clostridium_sensu_stricto_1 were more abundant in the GAMG group.…”

“…For example, sucralose decreased Lactobacillus, which could promote the production of SCFAs, and aspartame increased Ruminococcus, which was related with low levels of SCFAs. 28,40 Intake of inulin, grain fiber, and cymbidium polysaccharide can increase SCFAs by increasing SCFA-producing bacteria, relieve symptoms of type 2 diabetes, and improve insulin sensitivity. 42,43 Previous findings have shown that SCFAs have beneficial effects on blood glucose control, insulin resistance reduction, and inflammation relief.…”