Study shows how a specific gut bacterium influences infant immune system

Research published today in the journal Cell is the first to establish how a specific gut bacterium, activated Bifidobacterium infantis EVC001 (B. infantis), influences immune system development in infants, and could thereby reduce the risk of allergic and autoimmune conditions later in life.

While prior studies have shown a correlation between a lack of beneficial bacteria in the infant gut and the development of allergies and autoimmune diseases, this groundbreaking research, Bifidobacteria-mediated immune system imprinting in early life, found the presence of bifidobacteria, specifically the B. infantis EVC001 bacterial strain, early in a breastfed infant's life, programs naïve immune cells away from responses associated with immune-related conditions while producing regulatory cells that improve the body's ability to control inflammation.

The study also confirms the critical window of opportunity for impacting immune system development and reducing systemic inflammation is within the first 100 days of infancy.

The immune system normally guards against bacteria and viruses by marshalling specific immune T-cells to recognize and attack the foreign invaders in the body. The adaptive immune system at birth is naturally a blank slate; it has had very little exposure to viruses or dangerous bacteria, so immune cells, called naïve T-cells, have yet to be programmed accordingly.

In immune disorders and allergies, these cells are misprogrammed early on, by harmful bacteria or inflammation, to attack normal healthy cells in the body. Researchers have been working to determine how this misprogramming happens, to enable clinicians with solutions to reduce the risk of childhood allergic and autoimmune conditions.

Study details

For the study, researchers found that infants who lacked beneficial microbes able to metabolize complex sugars in breast milk, human milk oligosaccharides (HMOs), had disordered development of immune cell networks and significantly increased systemic inflammation.

Furthermore, in vitro experiments showed that gut bacterial metabolites and host factors from breastfed infants that lacked B. infantis EVC001 in their gut microbiome programmed naïve immune cells toward Th2 and Th17, two immune cell types associated with the development of autoimmune and allergic diseases.

In contrast, breastfed infants fed B. infantis EVC001 skewed those naïve immune cells toward Th1, an immune cell type that allows the body to properly react and rid itself of dangerous pathogens. Researchers also found far greater levels of interferon Beta (IFNβ) in the B. infantis EVC001 isolates, which is an important regulatory mediator that improves the body's ability to control inflammation and viral infections.

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.

More than 90 percent of newborns have a severe deficiency of B. infantis; 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."

Dr. Bethany Henrick, PhD, Study First and Corresponding Author and Director of Immunology and Diagnostics, Evolve BioSystems

The study examined the development of immune system changes in 208 infants born at the Karolinska University Hospital in Sweden between April 2014 and December 2019, evaluating bifidobacterial species and other microbes expressing HMO utilization genes. To further assess the beneficial effects of HMO utilization gene expressing microbes, a second cohort of the study involved 40 breastfed infants in California, with half receiving B. infantis EVC001, a strain of Bifidobacterium possessing all HMO utilization genes, and the other half given no supplementation.

"These are important findings 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," 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.

Source:
Journal reference:

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

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