The Probiotic Lactobacillus GG may Augment Intestinal Host Defense by Regulating Apoptosis and Promoting Cytoprotective Responses in the Developing Murine Gut

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Abstract
Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality in preterm infants. Although its pathogenesis is poorly understood, inappropriate apoptosis of the mucosal epithelia has been implicated. Recent clinical trials have shown that probiotics may reduce the incidence of NEC, and probiotics have been shown to suppress intestinal epithelial apoptosis in cultured cells. However, little is known about their mechanism of action in the developing intestine in vivo. Here, we confirm that the probiotic Lactobacillus rhamnosus GG (LGG) reduces chemically induced intestinal epithelial apoptosis in vitro. Furthermore, we report for the first time that LGG administered orally to live animals can reduce chemically induced epithelial apoptosis ex vivo, as measured by staining for active caspase 3 and terminal deoxynucleotidyltransferase. Using cDNA microarray analysis from the intestine of live, orally inoculated mice, we show that LGG up-regulates a battery of genes with known and likely cytoprotective effects. These studies indicate that probiotics such as LGG may augment intestinal host defenses in the developing intestine by stimulating antiapoptotic and cytoprotective responses. Because apoptosis may be a precursor to NEC, understanding the mechanism behind probiotic modulation of apoptotic pathways may allow for development of more specifically targeted therapies or preventive strategies in the future.