Lactobacillus reuteristrains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-κB signaling in the intestine
| Autor: | Nicole Y. Fatheree, Jon Marc Rhoads, Nisha Mangalat, Yuying Liu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Limosilactobacillus reuteri
Physiology Inflammation/Immunity/Mediators Proinflammatory cytokine Microbiology law.invention Enteritis Rats Sprague-Dawley Probiotic Enterocolitis Necrotizing law Physiology (medical) medicine Animals Ileitis RNA Messenger Inflammation Enterocolitis Hepatology biology Reverse Transcriptase Polymerase Chain Reaction NF-kappa B Gastroenterology food and beverages biology.organism_classification medicine.disease digestive system diseases Animals Suckling Rats Lactobacillus reuteri Toll-Like Receptor 4 Animals Newborn Gene Expression Regulation Necrotizing enterocolitis Immunology TLR4 Cytokines medicine.symptom Signal Transduction |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 302:G608-G617 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00266.2011 |
| Popis: | Necrotizing enterocolitis (NEC) is the leading gastrointestinal cause of mortality and morbidity in the premature infant. Premature infants have a delay in intestinal colonization by commensal bacteria and colonization with potentially pathogenic organisms. Lactobacillus reuteri is a probiotic that inhibits enteric infections, modulates the immune system, and may be beneficial to prevent NEC. In previous studies, L. reuteri strains DSM 17938 and ATCC PTA 4659 differentially modulated inflammation in vitro; however, the strains had equivalent anti-inflammatory responses in LPS feeding-induced ileitis in neonatal rats in vivo. The impact of these two strains in the prevention of NEC has not been previously investigated. NEC was induced in newborn rats by orogastric formula feeding and exposure to hypoxia. L. reuteri was added to the formula to prevent NEC. NEC score, Toll-like receptor (TLR)-signaling genes, phospho-IκB activity, and cytokine levels in the intestine were examined. Both strains significantly increased survival rate and decreased the incidence and severity of NEC, with optimal effects from DSM 17938. In response to probiotic, mRNA expression of IL-6, TNF-α, TLR4, and NF-κB was significantly downregulated, while mRNA levels of anti-inflammatory cytokine IL-10 were significantly upregulated. In parallel, L. reuteri treatment led to decrease intestinal protein levels of TLR4 and cytokine levels of TNF-α and IL-1β in newborn rats with NEC. Both strains significantly inhibited not only intestinal LPS-induced phospho-IκB activity in an ex vivo study but also decreased the levels of phospho-IκB in the intestines of NEC rat model. Cow milk formula feeding produced a similar but milder proinflammatory profile in the intestine that was also ameliorated by 17938. Our studies demonstrate that each of the two L. reuteri strains has potential therapeutic value in our NEC model and in enteritis associated with cow milk feeding. These results support the concept that L. reuteri may represent a valuable treatment to prevent NEC. |
| Databáze: | OpenAIRE |
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