Bifidobacteria-mediated immune system imprinting early in life

Henrick et al., Bifidobacteria-mediated immune system imprinting early in life, Cell (2021), https://doi.org/ 10.1016/j.cell.2021.05.030

There is mounting evidence to suggest that during the first 3 months of life, the infant gut microbiome is crucial for immune development. Specialised 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) which cannot be digested by humans. Evolution has provided selective advantages to beneficial microbes like Bifidobacterium longum by giving them the ability to metabolise HMOs.1

In this 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 utilisation from the metagenome, is 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 polarisation experiments, including targeted transcriptome and protein profiling by BD Rhapsody™ single-cell RNA sequencing, and fecal cytokine measurements in the study.

The authors propose that there is a transient immune response to colonising microbes during the first few weeks of life. The colonisation of the gut microbiome is by itself, an important determinant of this immune response. Bacteria expressing HMO-utilisation genes influence the immune-microbe interactions by reducing inflammatory responses. In breastfed infants who were given Bifidobacterium infansis EVC001, a bacterium that expresses HMO-utilisation 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 colonisation 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 colonisation during a key window of immunological development, where opportunities exist for supplementing the gut microbiome with potential benefits for the infant. 2

Read the full article in Cell here.


1
Sela, D.A., Chapman, J., Adeuya, A., et al. (2008). The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proc. Natl. Acad. Sci. USA 105, 18964–18969.
2 Henrick et al., Bifidobacteria-mediated immune system imprinting early in life, Cell (2021), https://doi.org/10.1016/j.cell.2021.05.030
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