Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine

• Published in: Pediatric research Vol. 88; no. 2; pp. 209 - 217
• Main Authors: Meng, Di, Sommella, Eduardo, Salviati, Emanuela, Campiglia, Pietro, Ganguli, Kriston, Djebali, Karim, Zhu, Weishu, Walker, W. Allan
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2020; Nature Publishing Group
• Subjects: Basic Science Article; Gastrointestinal diseases; Medicine; Medicine & Public Health; Necrosis; Pediatric Surgery; Pediatrics; Premature birth; Probiotics
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/s41390-019-0740-x

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.