New clinical data highlight unique enzymatic activity of B. infantis EVC001 in infant gut

Evolve BioSystems, Inc. today announced new data published this week in

Journal of Functional Foods

, showing for the first time that term, breastfed infants fed activated

Bifidobacterium longum subsp. infantis

EVC001 (

B. infantis

EVC001) experience improved metabolism of protein-bound glycans from human milk, compared to matched controls. Not only do these new data provide greater mechanistic understanding of how

B. infantis

selectively utilizes the glycans from human milk as growth substrate but may also provide a basis for facilitating

B. infantis

colonization in formula fed infants via utilization of bovine derived N-glycans. The paper is available at:

https:/

/

www.

sciencedirect.

com/

science/

article/

pii/

S1756464619304098

Although EndoBI-1, an enzyme unique to

B. infantis

, has previously been shown to release N-glycans from native bovine milk glycoproteins in vitro, this is the first study to clinically demonstrate this activity in breastfed infants fed

B. infantis

EVC001. These findings indicate that N-glycans from milk glycoproteins, whether derived from human or bovine sources, may contribute to colonization of

B. infantis

EVC001 in the infant gut.

B. infantis

is an infant-adapted gut bacterium uniquely capable of dominating the infant gut during exclusive breastfeeding, mainly through the well documented utilization of free human milk oligosaccharides (HMO). This key infant gut symbiont has been shown to create a protective environment in the infant gut during the early months of life via pathogen suppression, resulting in reduced virulence factors, a decreased abundance of antibiotic resistance genes, and reductions in colonic mucin degradation (1-4). These new data show that

B. infantis

is also capable of selectively releasing protein bound N-glycans from human milk glycoproteins in vivo. N-glycans from lactoferrin, in particular, are known to contribute to the antimicrobial activity of this protein and other glycans released by this enzyme may play an additional role in supporting the growth of

B. infantis

EVC001 in vivo.

“We are thrilled to see that the earlier in vitro work on this unique enzymatic activity of

B. infantis

is now demonstrated clinically here in breastfed infants,” says Dr. Steven Frese, Director of Microbiology at Evolve BioSystems and corresponding author of the study. “The important role and mechanism of this key infant gut bacterium in early life are becoming increasingly clear, but there is published evidence suggesting that the prevalence of

B. infantis

in US-born infants has been rapidly declining over the past 100 years (5). Therefore, these data are encouraging as we continue to develop effective methods of addressing infant gut dysbiosis. This work was really made possible because of an international collaboration with scientists at Çanakkale Onsekiz Mart University in Turkey, who have extensively characterized this enzyme.”

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About Evolve BioSystems

Evolve BioSystems, Inc.

is a privately-held microbiome company dedicated to developing the next generation of products to establish, restore, and maintain a healthy gut microbiome. Evolve is a spin-off from the Foods for Health Institute (FFHI) at the University of California, Davis and builds on more than a decade of research into understanding the unique partnership of the infant gut microbiome and breast milk components. Having led to the development and commercial launch of products to resolve newborn gut dysbiosis, including Evivo® for infants and GlycoGuard® for nursing foals and pigs, Evolve’s discovery platform is now being applied to solving gut dysbiosis throughout the human life cycle as well as other animal species. In addition to the landmark proof-of-concept trial, Evolve is undertaking further clinical studies to build out its suite of microbiome-based solutions.

References

1. Frese, Steven A.,

et al

. “Persistence of Supplemented

Bifidobacterium longum subsp. infantis

EVC001 in Breastfed Infants.”

MSphere

2.6 (2017): e00501-17.

2. Casaburi, Giorgio, and Steven A. Frese. “Colonization of breastfed infants by

Bifidobacterium longum subsp. infantis

EVC001 reduces virulence gene abundance.”

Human Microbiome Journal

9 (2018): 7-10.

3. Casaburi

et al

. Early-life gut microbiome modulation reduces the abundance of antibiotic resistant bacteria.

Antimicrobial Resistance & Infection Control

(2019)

4. Karav, Sercan, Giorgio Casaburi, and Steven A. Frese. “Reduced colonic mucin degradation in breastfed infants colonized by

Bifidobacterium longum subsp. infantis

EVC001.”

FEBS open bio

8.10 (2018): 1649-1657.

5. Henrick, Bethany M.,

et al

. “Elevated fecal pH indicates a profound change in the breastfed infant gut microbiome due to reduction of

Bifidobacterium

over the past century.”

MSphere

3.2 (2018): e00041-18.