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Thursday, October 28, 2021

Probiotic boosts beneficial bacteria in bellies of breastfed babies

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Bacteria that break down breast milk colonize newborns better with Evivo probiotic

Pediatricians and microbiologists have shown that a short dose of a probiotic product given to breastfed newborns can have enduring impacts on their gut microbiomes. The probiotic Evivo boosts the presence of Bifidobacterium longum infantis, a beneficial bacteria that specializes in breaking down complex sugars found in human breast milk.

“The cool part of this story is here is one particular kind of bacteria that is really good at consuming human milk oligosaccharides — better than anybody else,” said Dr. Mark Underwood, who serves as chief of pediatric neonatology at UC Davis Medical Center. “And here’s the mom who is making these sugar molecules and putting them into her milk at great cost to herself. The bottom line is that the mom seems to be shaping the microbiota — or the composition of the bacteria in the gut — by putting these sugars into her milk to try to selectively feed healthy bacteria.”

Human breast milk is largely composed of lactose and fat, but substantial amounts of protein and human milk oligosaccharides are present. HMOs are complex chains of sugar that humans cannot digest. B. infantis is the only known bacteria that is equipped with the enzymes to break down all known HMOs found in human breast milk. These tools give it an advantage in colonizing space in the intestines of breastfed human infants and clearing out pathogenic bacteria, which can produce inflammatory enterotoxins.

Although young infants born in nations such as Gambia and Bangladesh have high levels of B. infantis in their guts, babies born in nations such as the United States have much lower levels of the beneficial bacteria, with the gulf widening over the last century. More pathogenic bacteria have taken the place of B. infantis in American babies’ guts.

“It’s most likely that a combination of interventions resulted in this effect,” said Steve Frese, the associate director of research and development at Evolve Biosystems. “Formula feeding reduces the abundance of human milk oligosaccharides that B. infantis depends on, caesarean sections reduce the ability of B. infantis to be transferred, and on top of that, this is an organism sensitive to penicillin antibiotics — which most kids get early in life at least a few times — and mothers are often given around birth to prevent Group B Streptococcus infection of infants or as antibiotics for C Section.”

After giving Evivo to breastfed babies between days seven and 28, B. infantis levels spiked from around 30 percent to 80 percent of all bacteria measured in stool. At day 60, after 32 days of not taking the supplement, the levels of B. infantis remained remarkably stable, a departure from typical probiotic responses.

“What we saw was dramatically different from any other probiotic study I’ve ever seen,” Underwood said. “Most of the time, when you give somebody a probiotic, you can measure small amounts of the probiotic in the stool. As soon as you stop giving it, it goes back to the way it was.”

Part of the unique response to B. infantis supplementation likely lies in its ancient adaptations to live in the human gut and break down milk sugars as a food source.

“Our hypothesis was that we didn’t need to keep them on a probiotic for weeks or months,” Underwood said. “We could just give a short course, and then as long as they were still getting human milk — as long as they were breastfed — those bacteria we gave as the probiotic should be able to outcompete the other bacteria and be the dominant strain. That’s what we saw.”

Besides consuming HMOs, which would normally be passed through the infant digestive tract, B. infantis creates short chain fatty acids as a byproduct. These acids help to lower the pH in the intestines, energizing intestinal cells to tighten junctions with neighboring cells and creating an uncomfortable environment for pathogenic bacteria.

Infant formula contains mostly lactose and other simple sugars that feed many types of bacteria, some of which are linked to poor gut health. Breastfeeding a baby helps B. infantis outcompete bacteria which can create inflammatory compounds in the belly.

“We see in the literature that when babies have higher levels of these pathogens early in life, they’re at higher risk for allergic diseases,” said Jennifer Smilowitz, the associate director of the Human Studies Research Program at the Foods for Health Institute. “We see higher rates of asthma, allergies, a type of eczema and type I diabetes. These are all immune-related diseases which are higher in people, adults and children, when they have higher levels of pathogens in their guts in infancy or early life.”

Infants are quickly colonized by bacteria during birth and being exposed to the world outside of the womb. Babies delivered vaginally are first colonized by microbes in the birth canal, while babies born via Caesarean section are first colonized by bacteria from medical equipment and mother’s skin. Since B. infantis is anaerobic, it’s unlikely to survive well on skin.

“We think mom has a constitutive amount in her colon, and during labor and normal delivery, it is passed into the baby,” Smilowitz said.

After analyzing commercial probiotics advertised as containing B. infantis, researchers found all but one product contained different types of Bifidobacterium than what the packaging suggested. Such products would not help a breastfeeding baby colonize their gut with beneficial B. infantis or improve gut health.

“They are so functionally different, but they look so similar when you do DNA sequencing,” Smilowitz said. “David Mills’ lab was one of the first to develop methods to differentiate the two. You’ve got all these products on the market claiming to have B. infantis, but they actually have B. longum.” B. infantis is being packaged into a product called Evivo by Davis startup company Evolve Biosystems, founded by UC Davis faculty members to translate academic research into tangible impacts for the community. Future experiments will look into how long the increases in Bifidobacterium concentration last, how older infants respond to Evivo treatments and how changes in the infant microbiome can affect health in adolescence and adulthood.

 

 

Written by: George Ugartemendia — science@theaggie.org

 

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