Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine
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 prot...
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Published in | Pediatric research Vol. 88; no. 2; pp. 209 - 217 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.08.2020
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
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.
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.
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AUTHOR CONTRIBUTIONS DM oversaw all experiments; ES, PC and ES analyzed the B. infantis fractions and identified ILA; KG, KD and WZ contributed to ELIZA and LDH assay analysis, cell line maintenance and mouse experiments; WAW conceived of the research plan and analyzed experimental data. |
ISSN: | 0031-3998 1530-0447 |
DOI: | 10.1038/s41390-019-0740-x |