Evolve study reveals B. infantis strain shapes babies’ immunity via HMO metabolism

18 Jun 2021 --- Evolve BioSystems’ activated Bifidobacterium infantis EVC001 bacterial strain has been found to influence breastfed infants’ immune systems. This potentially reduces the risk of allergic and autoimmune conditions later in life.

The findings point to the “disturbing fact” that babies lacking B. infantis – now the norm in developed countries – can’t properly metabolize human milk oligosaccharides (HMOs), according to lead author Dr. Petter Brodin, professor of pediatric immunology at the Karolinska Institute in Sweden.

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.

“However, the findings also show that there’s a simple fix. Giving breastfed babies B. infantis EVC001 early in infancy can shut down inflammatory processes and reduce the lifetime risk of developing immune-mediated diseases,” he adds. 

Specifically, the presence of the strain was found to program naïve immune cells away from responses associated with immune-related conditions while producing regulatory cells that improve the body’s ability to control inflammation.Evolve BioSystems is a portfolio company of Horizons Ventures, Cargill, Manna Tree Partners, The Bill & Melinda Gates Foundation and Johnson & Johnson Development Corporation. 

Reinforcing immunity
Now published in Cell, the study details that infants lacking the HMO-metabolizing beneficial microbes had disordered development of immune cell networks and significantly increased systemic inflammation.

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

However, 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.

Controlling inflammation
There were also 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.

The research also shows how the bacterial strain can fully metabolize HMOs produced by the bacterial metabolite indolelactate (ILA). ILA, in turn, amplifies a broadly immunoregulatory factor, Galactin-1, effectively silencing Th2 and Th17.

“For the first time we’ve been able to demonstrate the unique ability of B. infantis EVC001 to fully break down HMOs,” says Dr. Bethany Henrick, first author of the study and director of immunology and diagnostics at Evolve BioSystems.

“The abundance of HMO utilization genes in the microbiome is directly correlated with decreased enteric and systemic inflammation.”The adaptive immune system at birth is naturally a blank slate.

 An “exciting step forward”
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. Specifically, the researchers evaluated 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, US, with half receiving B. infantis EVC001 and the other half given no supplementation.

“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,” details Henrick. 

Moves for B. infantis
In recent months, the infant nutrition industry has been eying offerings beyond formula. In February, Evolve BioSystems landed US$55 million for the commercialization of its “next generation of probiotic.”

A recent Lallemand review found that its Probiokid formula – which contains a different B. infantis strain – can help improve childhood maladies like unresolved diarrhea and iron deficiency anemia. 

Another study revealed that B. infantis persists in the guts of breast milk-fed babies for up to a year. 

Edited by Katherine Durrell