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Early Life Imprinting and Immune System Responses to Bifidobacteria Colonization

There is mounting evidence to suggest that during the first three months of life the infant gut microbiome is crucial for immune development. Specialized microbes in the infant gut that rely on breast milk for nutrients play a key role in immune-microbe interactions.1 Such interactions can influence the risk of allergies, asthma and other inflammatory disorders. Human breastmilk contains abundant human milk oligosaccharides (HMOs) that cannot be digested by humans. Evolution has provided selective advantages to beneficial microbes like Bifidobacterium longum, giving them the ability to metabolize HMOs.1

In an article published by the group of Petter Brodin at the Karolinska University Hospital, Sweden, the authors have aimed to demonstrate that the lack of bifidobacteria and, in particular, the depletion of genes necessary for HMO utilization from the metagenome are associated with systemic inflammation and immune dysregulation in early life. 

The authors have used blood immune cell profiling by mass cytometry, immune plasma profiling and fecal metabolomics, T cell polarization experiments, including targeted transcriptome and protein profiling using the BD Rhapsody™ Single-Cell Analysis System, RNA sequencing and fecal cytokine measurements in the study.

The authors propose that there is a transient immune response to colonizing microbes during the first few weeks of life. The colonization of the gut microbiome is, by itself, an important determinant of this immune response. Bacteria expressing HMO-utilization genes influence immune-microbe interactions by reducing inflammatory responses. In breastfed infants who were given Bifidobacterium infansis EVC001, a bacterium that expresses HMO-utilization genes, the authors noticed the silencing of intestinal T cell helper 2 (Th2) and Th17 cytokines, along with an induction of interferon β (Infβ). HMO metabolites like indolelactate and indole-3-lactic acid (ILA), found in abundance in the fecal water of EVC001-fed infants, were found by the authors to upregulate (in vitro) the immunoregulatory galectin-1, which is known to limit T cell activation in Th2 and Th17 cells. 

The authors propose that an immunological sequence of events that are triggered by microbial colonization results either in a balanced immune-microbe relationship or varying degrees of intestinal and systemic inflammation and perturbed T cell regulation. They also propose that their results highlight the importance of early microbial colonization during a key window of immunological development, where opportunities exist for supplementing the gut microbiome with potential benefits for the infant.2

Read the Cell article, “Bifidobacteria-mediated immune system imprinting early in life.”

1. Sela DA, Chapman J, Adeuya, A, et al. The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proc Natl Acad Sci USA. 2008;105(48):18964-18969. doi: 10.1073/pnas.0809584105

2. Henrick BM, Rodriguez L, Lakshmikanth T, et al. Bifidobacteria-mediated immune system imprinting early in life. Cell. 2021;184(15):3884-3898.e11. doi: 10.1016/j.cell.2021.05.030



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