Study unlocks how key bacterium trains infant immune system

By Stephen Daniells contact

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© tatyana_tomsickova / Getty Images
© tatyana_tomsickova / Getty Images

Related tags: Bifidobacterium infantis, infant microbiome

Bifidobacterium infantis EVC001 may influence immune system development in infants, says a new study from Evolve BioSystems that highlights the potential to reduce the risk of allergic and autoimmune conditions later in life.

Analysis of 208 infants born at the Karolinska University Hospital in Sweden between 2014 and 2019 revealed that infants with a B. infantis​ deficiency were unable to metabolize human milk oligosaccharides (HMOs) in breast milk and had disordered development of immune cell networks and significantly increased systemic inflammation.

This inflammation was driven by “aberrant Th2 and Th17 responses”​, said the study’s authors. Th2 and Th17, two immune cell types associated with the development of autoimmune and allergic diseases.

Data published in the journal Cell​ indicated that those naïve immune cells skewed toward Th1 in an additional cohort of breastfed infants in California. Th1 is an immune cell type that allows the body to properly react and rid itself of dangerous pathogens.

In addition, the researchers also found higher levels of an important regulatory mediator that improves the body’s ability to control inflammation and viral infections called interferon Beta (IFN-beta) in the B. infantis​ EVC001-fed infants.

Infant guts lacking B. infantis

According to Evolve Biosystems, B. infantis​ used to dominate the guts of babies born in developed countries, and still dominates those of babies in developing countries where allergies and autoimmune disorders are far less prevalent.

B. infantis​ crowds out pathogenic bacteria in the gut and has been shown to digest human milk oligosaccharides in breast milk that babies are otherwise incapable of processing, improving gut barrier function, reducing intestinal permeability, and downregulating gut inflammation.

“More than 90% of newborns have a severe deficiency of ​B. infantis,” ​explained Bethany Henrick, PhD, first and corresponding author of the study and Director of Immunology and Diagnostics at Evolve BioSystems. “This study is an exciting step forward in our understanding of the role of ​B. infantis EVC001 in the positive programming of immune cells and how it actually changes the trajectory of immune system development to protect against inflammation.

“For the first time we’ve been able to demonstrate that the unique ability of ​B. infantis EVC001 to fully break down HMOs and the abundance of HMO utilization genes in the microbiome is directly correlated with decreased enteric and systemic inflammation.”

Study details

For the first part of the study, the Dr Henrick and her collaborators from the University of Nebraska, Karolinska Institutet, the University of California, Davis, and the University of Nevada, Reno, examined the development of immune system changes in 208 infants in Sweden and found that a lack of bifidobacteria, and a depletion of genes required to use HMOs, were associated with systemic inflammation and immune dysregulation.

They then performed an intervention trial in California with 40 breastfed infants, half of whom received B. infantis​ EVC001 (a strain that does possess all HMO utilization genes).    

This trial revealed that B. infantis​ EVC001 skewed the naïve immune cells toward Th1 and led to far greater levels of IFN-beta. Additionally, the research shows that the unique genetic capacity of B. infantis EVC001 to fully metabolize human milk oligosaccharides (HMOs) produced the bacterial metabolite indolelactate (ILA).  ILA, in turn, amplifies a broadly immunoregulatory factor, Galactin-1, effectively silencing Th2 and Th17.

“These are important findings,”​ said Dr. Petter Brodin, MD, PhD, consultant pediatrician and lead author of the study and Professor of Pediatric Immunology at the Karolinska Institute in Sweden, “because, while they point to the disturbing fact that infants lacking ​B. infantis - unfortunately, now the norm in developed countries - can’t properly metabolize HMOs and are missing the critical window to develop a healthy immune system, it also shows that there’s a simple fix; feeding breastfed babies ​B. infantis EVC001 early in infancy can shut down inflammatory processes and reduce the life-time risk of developing immune-mediated diseases.”

Source: Cell
Published online ahead of print, doi: 10.1016/j.cell.2021.05.030
“Bifidobacteria-mediated immune system imprinting early in life”
Authors: B.M. Henrick et al.

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