Of mice and flies: How scientists are discovering growth-promoting probiotics that could benefit malnourished children

In countries where parents have access to modern medical care, they bring a new baby to regular checkups through its first years of life. The parents proudly report the milestones: clapping, crawling, drinking from a cup—and of course, medical staff carefully track the baby’s growth.

But in some places and for some children, the steady upward slant on the growth chart is not guaranteed. Malnutrition or undernutrition can prevent both the weight gain and the linear growth expected of healthy young children.

It’s a big problem to tackle, growth promotion. Because the stakes for a malnourished child’s future health are high, and it’s not as easy as just giving him or her the right foods. Some malnourished children who start receiving all the proper nutrients do not resume a normal growth pattern and continue to experience health complications. So what’s the rest of the story?

Scientists have been amassing more and more evidence—from both humans and animals—that the gut microbiota is a key factor in determining the growth of malnourished children.

A landmark study from 2014 found that children with severe acute malnutrition (SAM) have “immature” gut microbial communities for their chronological age, which do not return to normal when the children receive ready-to-use therapeutic foods (RUTFs). Researchers surmised the abnormal gut bacteria composition could partly account for the lack of proper growth, even after the kids’ nutritional needs are met. Already, medical professionals know children with SAM fare better if they receive antibiotics (which potentially change the gut microbiota) along with the therapeutic foods: the World Health Organization recommends these children receive antibiotics when they’re treated in their communities. But this approach is far from optimal and new approaches are urgently needed to prevent complications later in life when children don’t grow as they should.

François Leulier, researcher at the Institute of Functional Genomics of Lyon and Research Director at the French National Center for Scientific Research, is one of the scientists working on this problem. His approach is to study malnutrition and growth in different creatures to figure out what might be happening in humans.

“We start with a basic biological question,” says Leulier in an interview with GMFH editors, explaining that his approach is to initially work with simple models and test the most promising ideas in models that have longer lifespans and increasingly complex body systems: fly, mouse, and eventually, human.

“We’ve normally used a fly model,” Leulier says. “Now… the idea was to test whether the observation that we made using the insect model was translatable to the mouse models.”

In work from Leulier’s lab published in 2016, he and his colleagues found the presence or absence of a gut microbiota significantly affected how mice grew when they were chronically undernourished. “What is very striking is when you compare the growth pattern of germ-free animals to conventional animals that carry a microbiota, you see a major difference in their ability to buffer the [negative] effect of the chronic undernutrition,” he says. So when undernourished, the growth of germ-free animals was stunted dramatically, while the growth of the animals with a normal complement of gut microbes was altered less.

“Clearly, what we see in different animal models is that… the intestinal microbiota is really important in shaping how the host responds to chronic undernutrition,” he says.

Noting that, for humans, maturation of the gut microbiota in childhood is a delicate process, he says, “Experimental results suggest that this altered maturation pattern of the intestinal community during the infant period is causal to the growth deficits that those juvenile animals or infants are showing.”

“The exact details in between—how the maturation occurs, [how] the lack of maturation of the microbiota [occurs], the consequences on the physiology of the organisms, and the biology underlying those phenomena—[are] not clear yet.” Understanding the mechanisms behind these phenomena is the challenge he and his colleagues are taking on.

Interestingly, certain strains of probiotic bacteria appeared to have an ‘outsized’ effect on growth. Leulier and colleagues had previously shown that, in flies, a particular bacterium called Lactobacillus plantarum promoted growth. Would the same apply to mice?

“The strains that were qualified as growth-promoting using the insect system were also showing some very marked effects on juvenile growth in the mouse model,” he reports. Because the growth appeared to depend on the presence of specific bacteria, Leulier believes certain strains of lactobacilli (and possibly strains from other bacterial groups) are intrinsically capable of promoting growth.

Currently the lab is investigating the possibility that the bacterial strains promoting growth do their work via the insulin-like growth factor 1, which is a key promoter of bone and overall growth in infants.

One day, a better understanding of how microbes impact the growth of children facing malnutrition could indeed save human lives—perhaps by yielding tools to complement the nutritional strategies used today. But Leulier says a probiotic strategy for improving children’s growth will not be without its complexities: “[It] won’t be so straightforward, because many of the microbes of the intestinal microbiota are still poorly characterized and still difficult to grow,” he says. Moreover, extensive testing would have to occur in clinical trials.

But Leulier keeps in mind the eventual goal, which is not really so far-fetched. “We could [imagine a] therapeutic strategy of re-feeding and also providing functional probiotic strains that would be dedicated to promoting growth of either animals or kids.”

 

 

Reference:

Schwarzer M, Makki K, Storelli G, et al. Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science. 2016; 351:854-857.

Kristina Campbell
Kristina Campbell
Science writer Kristina Campbell (M.Sc.), from British Columbia (Canada), specializes in communicating about the gut microbiota, digestive health, and nutrition. Author of the best selling Well-Fed Microbiome Cookbook, her freelance work has appeared in publications around the world. Kristina joined the Gut Microbiota for Health publishing team in 2014.  Find her on: GoogleTwitter