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Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated
Kriston Ganguli1, Di Meng, Samuli Rautava
1Mucosal Immunology Laboratory, Division of Pediatric Gastroenterology, Massachusetts General Hospital for Children, 114 16th St. (114-3503), Charlestown, MA 02192-4404, USA. kganguli@partners.org
American Journal of Physiology. Gastrointestinal and Liver Physiology
|November 10, 2012
Summary
Probiotic conditioned media (PCM) from Bifidobacterium infantis and Lactobacillus acidophilus may prevent necrotizing enterocolitis (NEC) by maturing infant intestinal immune responses. This study investigated the anti-inflammatory effects of these probiotic strains on infant gut cells and tissues.
Area of Science:
- Gastroenterology
- Immunology
- Neonatology
Background:
- Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory condition in premature infants.
- Immature innate immune responses contribute to NEC development following bacterial colonization.
- Clinical trials show probiotics reduce NEC incidence in very low birth weight infants.
Purpose of the Study:
- To investigate if secreted products from Bifidobacterium infantis and Lactobacillus acidophilus accelerate intestinal immune gene maturation.
- To determine if both probiotic strains are necessary for this protective effect against NEC.
- To elucidate the anti-inflammatory mechanisms of probiotic conditioned media (PCM).
Main Methods:
- Immature human enterocytes, intestinal xenografts, and NEC-IEC were exposed to PCM.
- IL-8 and IL-6 responses to inflammatory stimuli were measured.
- Innate immune gene expression (TLR2, TLR4, SIGIRR, Tollip) was analyzed.
- The role of Tollip was assessed using siRNA knockdown.
- Characteristics of the anti-inflammatory factor were determined.
Main Results:
- PCM significantly reduced inflammatory cytokine (IL-8, IL-6) production in immature intestinal models.
- PCM modulated the expression of Toll-like receptors (TLR2, TLR4) and negative regulators (SIGIRR, Tollip).
- Tollip knockdown reversed the anti-inflammatory effect of PCM.
- The anti-inflammatory factor is a small, stable molecule.
- B. infantis PCM demonstrated stronger anti-inflammatory effects than L. acidophilus PCM.
Conclusions:
- Probiotic conditioned media promotes the maturation of innate immune response gene expression in the infant gut.
- This maturation of immune response may explain the protective effects of probiotics against necrotizing enterocolitis.
- Strain specificity exists in the anti-inflammatory properties of probiotics.
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