Unlocking the Baby Gut Microbiome

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Oct 23, 2017

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Last year, scientists linked a deadly intestinal condition for which premature babies are commonly at-risk, to an imbalanced gut microbiome. Now, newer research is helping clarify the root cause of necrotizing enterocolitis – and identify a preventative treatment.

Researchers from the University of Geneva and the Swiss Federal Institute of Technology in Lausanne recently identified a gut “architect” gene, which acts as a blueprint for baby gut development in mice. (The human and mouse genomes are quite similar, and these findings can help pinpoint where to look for confirmation in human DNA.)

“All of the pups carrying [a mutated gut architect gene] were severely stunted during the suckling period and displayed an abnormal development of the small intestine,” explained Jozsef Zakany, the study’s first author and researcher at the University of Geneva’s Department of Genetics and Evolution.

In humans, critical gut development continues after birth through a unique interplay between breast milk and the baby’s gut microbiome. In I Contain Multitudes: The Microbes Within Us and a Grander View of Life, author Ed Young explains that human breast milk is primarily composed of lactose and fats, but the third-most plentiful ingredient is a vast variety of simple sugar combinations called human milk oligosaccharides (HMOs), an ideal source of energy – but not for infants, who can’t actually digest HMOs.

“H.M.O.s pass through the stom­ach and the small intestine unharmed, landing in the large intestine, where most of our bacteria live,” Young writes. “What if they aren’t food for babies at all? What if they are food for microbes?”

Research suggests these oligosaccharides are intended to nourish one specific microbe: B. infantis, of a larger class of bacteria (called Bifs) that flourish in the microbiome of breastfed infants, but not those of formula-fed babies. In return, B. infantis, as it digests the HMOs, releases short-chain fatty acids that feed the newborn’s gut cells; B. infantis also prompts the cells to close the natural gaps between them, thus reinforcing the intestinal walls and cutting off bad microbes’ access to the blood stream, among other, anti-inflammatory functions.

When this doesn’t happen, when breast milk isn’t assimilated throughout the gut, as in the case of a mutated architect gene, these gaps may not seal, leaving preemies’ intestinal wall, in extreme cases, susceptible to invasion by bad bacteria that can destroy it – that is, necrotizing enterocolitis. (When B. infantis gets lactose, instead of HMOs — as in the case of formula feeding — the critical bacteria survive, but its interaction with intestinal cells, and the baby gut development that fosters, is muted.)

Some are working on a treatment to help preemies close their intestinal gaps and compensate for the possible genetic gap behind them. Mark Underwood, a pediatrician and head of the NICU at UC Davis Children’s Hospital, is working on a way to infuse his premature patients with a combination of B. infantis and breast milk. Per Young:

“The food you feed these bugs is as important as the bugs themselves in getting them to grow and colonize a fairly hostile environment,” he told me. If the treatment works, breast milk could do for preemies what it does for their full-term brethren, nourishing baby and bacteria, infant and infantis, and preparing them for life ahead.

It is unknown whether mutations on the gut architect gene are behind the types of microbiome dysbiosis linked to less dire conditions that develop over time, such as allergies, asthma or diabetes. The next step in all of this will likely be to catalog the various possible mutations of the gene. But also to ask — what causes the mutation to begin with? This might be the missing link to the maternal health conditions associated with C-section delivery (and, notably, premature birth) that have led to C-section delivery being mistakenly blamed for infant gut dysbiosis. One thing is clear: Gut development starts – and can go awry – well before birth.

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Written By The Swaddle Team

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