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Breast Milk and Microbiota in the Premature Gut: A Method of Preventing Necrotizing Enterocolitis
1Pediatric Gastroenterology Department, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts, USA, Wwalker@mgh.harvard.edu.
Insights
Necrotizing enterocolitis (NEC) in premature infants may be prevented by breast milk metabolites. These compounds, including indole-3-lactic acid and short-chain fatty acids, reduce intestinal inflammation by modulating immune responses.
Area of Science:
- Neonatal immunology
- Gastroenterology
- Microbiome research
Background:
- Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory disease in premature infants.
- Immature immune responses and gut bacteria contribute to NEC pathogenesis.
- Current treatments are limited, emphasizing the need for prevention strategies.
Purpose of the Study:
- To investigate the anti-inflammatory mechanisms of breast milk components in preventing NEC.
- To identify specific metabolites and their pathways involved in immune modulation.
Main Methods:
- Analysis of breast milk components, including tryptophan and complex carbohydrates.
- Investigating the interaction of breast milk components with specific bacteria like Bifidobacterium infantis and Bacteroides fragilis.
- Assessing the impact of bacterial metabolites on immune signaling pathways, including aryl hydrocarbon receptor and NF-κB.
Main Results:
- Breast milk tryptophan and Bifidobacterium infantis yield indole-3-lactic acid, an anti-inflammatory metabolite that inhibits IL-8 response via aryl hydrocarbon receptor.
- Breast milk complex carbohydrates and Bacteroides fragilis interaction produce short-chain fatty acids with anti-inflammatory effects on the neonatal intestine.
Conclusions:
- Specific breast milk metabolites, indole-3-lactic acid and short-chain fatty acids, demonstrate significant anti-inflammatory properties relevant to NEC prevention.
- These findings suggest a potential therapeutic strategy for NEC prevention through targeted metabolite administration or modulation of the infant gut microbiome.
Abstract:
Necrotizing enterocolitis (NEC) is a devastating inflammatory condition of the intestine, which affects premature infants and causes untold damage. Its pathogenesis has to do with how colonizing bacteria interact with the immature newborn intestine. An immature innate immune response with increased TLR-4 on the cell surface and increased signaling molecules, such as NF-κB, can cause excessive inflammation. This is in conjunction with a decrease in the appearance of regulatory molecules which effect the control of innate responses. This condition is so devastating that it must be prevented and not treated. Fortunately, breast milk and probiotics can affect the condition leading to reduced inflammation. How does this effect work? We have shown that breast milk tryptophan and Bifidobacterium infantis result in a metabolite (indole-3-lactic acid) response, which is anti-inflammatory via inhibition of the aryl hydrocarbon receptor transcription factor which stimulates an IL-8 response. We have also shown that breast milk complex carbohydrates interacting with Bacteroides fragilis can cause short-chain fatty acids which exert anti-inflammatory effects on the newborn intestine. These breast milk metabolites could help prevent NEC if shown to be effective clinically.
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