M1198 Lactobacillus Rhamnosus GG Prevents Radiation Induced-Small Intestinal Injury in a MyD88 Independent, But COX2 Dependent Manner

Background. Radiation-induced intestinal injury is one of the side effects in patients receiving radiotherapy. The aim of the present study was to investigate the protective effect of XH-103 on radiation-induced small intestinal injury and to explore its mechanism. Methods. C57BL/6N mice were irradiated and treated with XH-103. Firstly, the survival rate of mice exposed to 9.0 Gy and 11.0 Gy total body irradiation (TBI) was examined. Subsequently, at 3.5 d after IR, the small intestinal morphological changes were examined by HE. The numbers of crypt cells, the villus height, the expression of Ki67 and Lgr5, and the apoptotic cells in the intestinal crypts were examined by immunohistochemistry. Furthermore, the expression of p53 and Bax was analyzed by WB. Results. Compared to the irradiation group, XH-103 improved the mice survival rate, protected the intestinal morphology of mice, decreased the apoptotic rate of intestinal crypt cells, maintained cell regeneration, and promoted crypt proliferation and differentiation. XH-103 also reduced the expression of p53 and Bax in the small intestine compared to the IR group. Conclusion. These data demonstrate that XH-103 can prevent radiation-induced intestinal injury, which is beneficial for the protection of radiation injuries.

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Feeding Formula Eliminates the Necessity of Bacterial Dysbiosis and Induces Inflammation and Injury in the Paneth Cell Disruption Murine NEC Model in an Osmolality-Dependent Manner

Nutrients ◽

10.3390/nu12040900 ◽

2020 ◽

Vol 12 (4) ◽

pp. 900

Author(s):

Shiloh R Lueschow ◽

Stacy L Kern ◽

Huiyu Gong ◽

Justin L Grobe ◽

Jeffrey L Segar ◽

...

Keyword(s):

Paneth Cell ◽

Cell Disruption ◽

Formula Feeding ◽

Intestinal Injury ◽

Intestinal Damage ◽

Dependent Manner ◽

Microbial Composition ◽

Small Intestinal Injury ◽

Milk Substitute ◽

Small Intestinal

Necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in preterm infants. Formula feeding is a risk factor for NEC and osmolality, which is increased by the fortification that is required for adequate growth of the infant, has been suggested as a potential cause. Our laboratory has shown that Paneth cell disruption followed by induction of dysbiosis can induce NEC-like pathology in the absence of feeds. We hypothesized adding formula feeds to the model would exacerbate intestinal injury and inflammation in an osmolality-dependent manner. NEC-like injury was induced in 14–16 day-old C57Bl/6J mice by Paneth cell disruption with dithizone or diphtheria toxin, followed by feeding rodent milk substitute with varying osmolality (250–1491 mOsm/kg H2O). Animal weight, serum cytokines and osmolality, small intestinal injury, and cecal microbial composition were quantified. Paneth cell-disrupted mice fed formula had significant NEC scores compared to controls and no longer required induction of bacterial dysbiosis. Significant increases in serum inflammatory markers, small intestinal damage, and overall mortality were osmolality-dependent and not related to microbial changes. Overall, formula feeding in combination with Paneth cell disruption induced NEC-like injury in an osmolality-dependent manner, emphasizing the importance of vigilance in designing preterm infant feeds.

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