Ameliorating gut microenvironment through staphylococcal nuclease-mediated intestinal NETs degradation for prevention of type 1 diabetes in NOD mice.
AIMS
Recent studies have revealed that neutrophil extracellular traps (NETs) provide negative feedback in the progression to chronic inflammation and contribute to the pathogenesis of multiple autoimmune diseases including type 1 diabetes (T1D). In addition, accumulating evidences suggest that gut immunity play a key role in T1D pathogenesis. Our study aimed to evaluate whether staphylococcal nuclease (SNase) targeting intestinal NETs can ameliorate the intestinal inflammatory environment and protect against T1D development in non-obese diabetic(NOD) mice.


MAIN METHODS
Degradation of NETs with SNase in vitro was examined using SYTOX green assay. NOD/LtJ mice were oral administration of Lactococcus lactisl (L. lactis) pCYT: SNase and blood glucose levels were monitored weekly. Several biomarkers of NETs formation, gut leakage and inflammation were determined using a commercial ELISA kit. T Cell phenotypes in peripheral immune system were analyzed in flow cytometry and fecal samples were isolated to investigate intestinal microbiota.


KEY FINDINGS
The oral delivery of SNase by L. lactis can decrease the NETs levels and ameliorate inflammation both in the intestine and pancreatic islets and finally effectively regulate the blood glucose levels of NOD mice. Meanwhile, zonulin and lipopolysaccharide levels also reduced in SNase-fed NOD mice, suggesting SNase could improve gut barrier function via intestinal NETs degradation. Furthermore, the abundances of the intestinal microbiota and butyrate-producing gut bacteria were also increased with SNase treatment.


SIGNIFICANCE
SNase shows potential for intestinal NETs to prevent T1D based on the gut-pancreas axis.
['Liang|Yixuan|Y|', 'Wang|Xiaoke|X|', 'He|Dongmei|D|', 'You|Qi|Q|', 'Zhang|Tingting|T|', 'Dong|Wanfa|W|', 'Fei|Jingjin|J|', 'Xing|Yun|Y|', 'Wu|Jie|J|']
D000818:Animals D001786:Blood Glucose D003922:Diabetes Mellitus, Type 1 D004195:Disease Models, Animal D065206:Extracellular Traps D000069196:Gastrointestinal Microbiome D007249:Inflammation D007422:Intestines D007515:Islets of Langerhans D051379:Mice D016688:Mice, Inbred NOD D008836:Micrococcal Nuclease
Type 1 diabetes Neutrophil extracellular traps Staphylococcal nuclease Intestinal microenvironment