Phenomena: Not Exactly Rocket Science

Raising an infant is an act of ecosystem engineering. You’re not just caring for a baby, but an entire world.

Right from birth, babies are colonised by legions of microbes that set up shop in their guts, skin, and more. These are vital. They help the growing human to digest its food, and to keep harmful microbes away. They are so important that newborns temporarily suppress their own immune system to give their microbial partners a chance to establish themselves.

Mum helps too. Her vaginal secretions provide her child with a starter pack of microbes. And her breast milk contains special sugars that seem to selectively nourish the gut bacteria that infants need.

Now, Eric Rogier from the University of Kentucky has found a milk antibody called SIgA also helps to set up the right community of gut microbes. Without it, young mice face long-lasting consequences, including several signs of inflammatory bowel diseases (IBD).  This antibody sets up a healthier environment in an infant’s intestinal tract, so they’re better prepared to withstand environmental problems later in life,” says Charlotte Kaetzel, who led the study.

Although the team only looked at mice, Kaetzel notes that several studies have found that breastfed babies are less likely to develop IBD later in life. “We’re not talking about black and white: you’re protected if you’re breastfed and not protected if you aren’t,” she says. “But I’d certainly argue that there’s a clear benefit.”

“We now recognize more and more that factors in breast milk influence the gut microbiota, which in turn sets up the immune system to have fewer chronic illnesses later in life,” says Allan Walker from Massachusetts General Hospital.

Milk contains a vast cocktail of molecules, and immunoglobin A (IgA or SIgA) is one of them. It’s an antibody found in our bodily secretions. We manufacture it in ridiculous amounts: around a teaspoon every day. It’s in milk, mucus, tears, saliva—anywhere where our cells shunt fluid into the outside world. Run a finger along any surface of your body and if it ends up wet, it probably has SIgA on it.

Mice and humans eventually make SIgA for themselves but in our earliest days of life, mother’s milk is the only source of the antibody. When Rogier engineered mutant mice that couldn’t produce SIgA in their milk, he found that their pups grew up with peculiar guts. They harboured with different communities of gut bacteria, and had more of certain groups that are seen in the guts of IBD patients. And some of these microbes ended up in unexpected places.

As a mouse grows up, its gut microbes interact with its own gut cells to create a sealed barrier that keeps foreign material out of the deeper intestinal tissue. The barrier is a good fence that makes for good neighbours. But if newborn mice can’t get SIgA from their mothers, their intestinal barriers are porous and bacteria pass into the underlying lymph nodes.

“These lymph nodes should be absolutely sterile,” says Kaetzel. “When you take them out of an adult mouse and culture them, you’ll find no bacteria. When we took lymph nodes from offspring who didn’t get SIgA in their milk, they were loaded with bacteria.”

The most abundant species was Ochrobactrum anthropi—an opportunistic bacterium that’s been linked to a growing number of infections in hospital patients. It also depends on oxygen, which is odd since most gut bacteria shun the stuff or, at most, tolerate it. “You typically see overgrowth of aerobic bacteria when you have inflammation,” says Kaetzel.

“Beneficial bacteria in the intestinal tract are crucial, but you don’t necessarily want them around too much, like overgrowing in the lymph nodes,” says Katie Hinde from Harvard University. “This study shows that ingested SIgA is instrumental for limiting bacterial invasion beyond the gut wall.”

These early changes persisted into adulthood and left the mice permanently susceptible to inflammation, even if they could eventually make SIgA for themselves. When the team added an inflammatory chemical called DSS into their drinking water, those that didn’t get the antibody from their mothers reacted more vigorously. They strongly activated several genes that have been linked to IBD in humans.

When it comes to such diseases, scientists often talk about a triad of contributing factors: the host’s own biology, their microbes, and environmental factors like food-borne illnesses that can trigger inflammation. “These mice had altered two sides of this triangle,” says Kaetzel. They didn’t get enough SIgA (a host factor), and they ended up with strange microbiota. The DSS closed the triangle and led to severe inflammation.

The team now wants to see if it’s possible to boost the intestinal health of a formula-fed infant by supplementing them with SIgA, or even if the purified antibody could help older children or adults with intestinal problems.

And, of course, their study highlights yet another benefit to breastfeeding. It’s unique in isolating the effect of a single (major) ingredient of milk, but Kaetzel notes that breastfed infants also get a wide spectrum of other helpful substances.

For example, it contains its own microbes. Lisa Funkhouser and Seth Bordenstein have speculated that the lymphatic system conveys bacteria from a mother’s guts into her mammary glands, where they can be taken up by suckling infants.

If pups that don’t get SIgA from their mothers have weird bacteria in their lymph nodes, could they then pass on different microbes to their own offspring, when the time comes for them to produce milk? “There could be some really exciting transgenerational consequences from not ingesting sIgA in mother’s milk,” says Hinde.

Reference: Rogier, Frantz, Bruno, Wedlund, Cohen, Stromberg & Kaetzel. 2014. Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. PNAS


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