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Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine.
- Source :
-
Pediatric research [Pediatr Res] 2020 Aug; Vol. 88 (2), pp. 209-217. Date of Electronic Publication: 2020 Jan 16. - Publication Year :
- 2020
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Abstract
- Background: Necrotizing enterocolitis (NEC), a necrotic inflammation of the intestine, represents a major health problem in the very premature infant. Although prevention is difficult, the combination of ingestion of maternal-expressed breastmilk in conjunction with a probiotic provides the best protection. In this study, we establish a mechanism for breastmilk/probiotic protection.<br />Methods: Ultra-high-performance liquid chromatography-tandem mass spectrometry of Bifidobacterium longum subsp. infantis (B. infantis) secretions was used to identify an anti-inflammatory molecule. Indole-3-lactic acid (ILA) was then tested in an established human immature small intestinal cell line, necrotizing colitis enterocytes, and other immature human enteroids for anti-inflammatory effects and to establish developmental function. ILA was also examined in immature and mature enterocytes.<br />Results: We have identified ILA, a metabolite of breastmilk tryptophan, as the anti-inflammatory molecule. This molecule is developmentally functional in immature but not mature intestinal enterocytes; ILA reduces the interleukin-8 (IL-8) response after IL-1β stimulus. It interacts with the transcription factor aryl hydrocarbon receptor (AHR) and prevents transcription of the inflammatory cytokine IL-8.<br />Conclusions: This molecule produced by B. infantis (ATCC No. 15697) interaction with ingested breastmilk functions in a complementary manner and could become useful in the treatment of all at-risk premature infants for NEC if safety and clinical studies are performed.
- Subjects :
- Animals
Anti-Inflammatory Agents pharmacology
Chromatography, High Pressure Liquid
Chromatography, Liquid
Cytokines metabolism
Enterocolitis, Necrotizing metabolism
Enterocytes
Humans
Hydrocortisone
Infant, Newborn
Inflammation
Interleukin-1beta metabolism
Interleukin-8 metabolism
Intestines growth & development
Intestines pathology
Male
Mice
Mice, Inbred C57BL
Milk, Human
Organ Culture Techniques
Probiotics
Receptors, Aryl Hydrocarbon metabolism
Tandem Mass Spectrometry
Bifidobacterium longum metabolism
Indoles metabolism
Tryptophan metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0447
- Volume :
- 88
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Pediatric research
- Publication Type :
- Academic Journal
- Accession number :
- 31945773
- Full Text :
- https://doi.org/10.1038/s41390-019-0740-x