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LACTOBACILLUS RHAMNOSUS SUPPRESSES EPITHELIAL APOPTOSIS BY UPREGULATING CYTOPROTECTIVE GENES IN THE IMMATURE GUT
Author(s) -
Lin Patricia Lanee Wei,
Nasr Tala R.,
Berardinelli Andrew,
Kumar Amrita,
Neish Andrew S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.899.14
Subject(s) - lactobacillus rhamnosus , apoptosis , tunel assay , biology , downregulation and upregulation , probiotic , ex vivo , necrotizing enterocolitis , in vivo , immunology , cancer research , medicine , gene , biochemistry , microbiology and biotechnology , genetics , bacteria
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants. Recently, inappropriate intestinal epithelial apoptosis has been implicated in its pathogenesis. Clinical trials suggest that probiotics may reduce NEC, and in vitro studies suggest that the probiotic Lactobacillus rhamnosus ( LGG ) may act by suppressing apoptosis in cultured epithelia. Here, we aimed to determine whether and how LGG may prevent NEC by reducing apoptosis in the developing gut in vivo. We fed 2 week old preweaned mice (maturity expected at 3 weeks) media with or without LGG (4h) and harvested small intestines for ex vivo apoptotic induction. LGG significantly reduced epithelial apoptosis as measured by staining for cleaved caspase 3 and TUNEL. To delineate mechanism, we used cDNA microarray which revealed that LGG upregulated a battery of known and candidate cytoprotective genes. The dual specificity phosphatase, DUSP3 was the most highly upregulated gene by microarray and qRT‐PCR. Further, we confirmed that oral LGG increased intestinal epithelial DUSP3 in immature mice by immunohistochemistry. DUSPs have been implicated in anti‐apoptotic, cytoprotective responses in a variety of systems by inhibiting MAPK signaling. These studies indicate that probiotics such as LGG may augment intestinal host defenses in the developing intestine by stimulating anti‐apoptotic, cytoprotective responses.