• Intestinal Microbiota Protect Children From Malnutrition

Intestinal Microbiota Protect Children From Malnutrition

Three new studies show that intestinal bacteria protect children from malnutrition and allow them to benefit from breast milk.

Malnutrition, the world’s leading cause of death before age 5, is a persistent challenge that is not always remedied by improvements in nutrition. This is because the community of gut microbes regulate growth, nutrient metabolism, and body weight.

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Lactobacilli strains promote growth of infant mice. Credit: Vincent Moncorgé, Science

Laura Blanton et al studied this effect by analyzing bacterial 16S ribosomal RNA in fecal samples collected from infants and children in Malawi. The children included in the analysis had varying degrees of undernutrition during their first 3 years of life.

In the 19 February issue of Science, Blanton et al report that undernourished children have an immature gut microbiota, compared with that of healthy children.

Blanton et al transplanted fecal samples from 6- and 18-month-old children with healthy growth patterns or varying degrees of undernutrition into young germ-free mice that were fed a representative Malawian diet.

Microbiota from the malnourished children, but not from healthy children, reduced growth, altered bone morphology, and produced metabolic abnormalities in the muscle, liver, and brains of the recipient mice.

“With all other things being equal, the presence of healthy microbes allowed mice to grow bigger across the board”, wrote The Washington Post.

However, co-housing mice with healthy and undernourished microbiota allowed the healthy microbiota to transfer into the guts of the undernourished mice (because mice eat each other’s feces), and restored their growth and metabolic function.

Several age-discriminatory taxa in the transplanted microbiota carried by recipient animals correlated with their growth rates. The authors found that Ruminococcus gnavus and Clostridium symbiosum alone restored growth to mice with the undernourishment-associated microbiota.

Blanton et al state that their findings provide evidence that gut microbiota immaturity can mediate growth effects of undernutrition. The age- and growth-discriminatory taxa they identified could be manipulated to prevent or reverse gut microbiota immaturity.

A second study in the same issue of Science identified 2 strains of gut microbes that maintain growth hormone activity in young mice that would otherwise develop growth hormone growth resistance because of malnourishment.

Martin Schwarzer et al had previously identified strains of Lactobacillus plantarum within the guts of fruit flies that affected their growth during juvenile periods, when nutrition and growth hormone signaling are required. The authors investigated the effects of these bacteria in germ-free mice, which produce significantly lower levels of growth hormone.

Schwarzer et al. found that germ-free juvenile mice were unable to recover normal growth compared to controls after switching to a better diet. However, germ-free juvenile mice that carried only the 2 strains of Lactobacillus plantarum gained significantly more weight. In other words, the 2 bacterial strains were almost as effective as the entire microbiota in supporting growth in the otherwise germ-free animals.

Together, the results of the 2 Science studies demonstrate how an altered gut microbiome, and specific strains of microbes, can affect growth and metabolism.

“Childhood undernutrition is a global, vexing, challenging, tragic health problem,” Jeffrey Gordon, senior author of the study by Blanton et al., told The Post. And even though mortality has dropped thanks to high-calorie therapeutic foods and other interventions, the problem persists.

“We still see stunted growth in these treated children,” Gordon said, explaining that many developmental and health problems seem to follow malnourished individuals. “There’s something we’re not repairing, something we’re missing.”

In an article published online February 19 in Cell, Mark Charbonneau et al investigated the relationship between microbes and nourishment in human breast milk. Gordon was also senior author on this article.

Charbonneau et al analyzed human milk oligosaccharides from 6-month–postpartum mothers in 2 Malawian birth cohorts. They found significantly lower levels of sialylated milk oligosaccharides, which are important for brain development, in milk from mothers with severely stunted infants.

To explore the association, Charbonneau et al colonized young germ-free mice with bacterial strains cultured from the fecal microbiota of a 6-month–old Malawian infant with stunted grown and fed the recipient mice a prototypic Malawian diet—with or without purified sialylated bovine milk oligosaccharides.

They found that the sialylated bovine milk oligosaccharides produced a microbiota-dependent augmentation in lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways that indicate a greater ability to utilize nutrients for anabolism.

These effects were also observed in gnotobiotic piglets using the same bacterial combination and Malawian diet.

Their findings indicate a microbiota-dependent relationship between sialylated milk oligosaccharides and infant growth.

Gordon explained to The Post that all the mice had same caloric intake and same gut microbes, yet the mice that received sialic acid in quantities comparable to healthy breast milk grew larger. And animals left germ ­free saw no boost from the addition of these sugars.

Gordon and colleagues believe that the growth benefits could depend on products created by bacteria as they consume sialic acid.

The Atlantic explained that the sialylated sugars change what the gut microbes are capable of. “They became more metabolically flexible,” Charbonneau told the publication. Healthy animals can switch to burning fat for energy when sugar isn’t available, but undernourished ones cannot. “With the milk sugars, that normal flexibility is restored.”

“There are food webs in the microbial community, and these bacteria living on sialic acid are just the primary consumers,” Gordon explained to The Post. “They transform it into products used by other microbes in the community. We need to be sure that none of those secondary consumers are dangerous.”

The Post wrote that this is of particular concern for malnourished children in Malawi, where a lack of clean water means that many guts are full of potentially dangerous pathogens ready to take over the gut. Researchers can’t recommend giving these children a boost of sialic acid — or any microbe­related food additive — without doing more research, as it could increase numbers of dangerous pathogens.

In support of this concept, Charbonneau et al found that 2 bacteria reacted especially vigorously to the influx of sialylated sugars. Bacteroides fragilis devoured the sugars and released chemicals that fed Escherichia coli. This is an important observation because many strains of E coli are harmless residents of the gut, but some can cause disease.

David A. Relman (Stanford University School of Medicine) praised Gordon’s research to The Post but urged caution in assuming its results would hold true in humans.

“Because germ-­free animals are born with grossly altered anatomy and function, provision of a new first-­time microbiota to these animals may not perfectly mimic what happens in a natural setting or mimic the much more complex circumstances of newborn children in diverse sociocultural and environmental settings,” Relman said. But he believes therapies that rely on cultivating our microbial communities are worth pursuing.

“Even if the microbiota is a relatively small contributory factor for nutritional status, it is potentially modifiable, and hence, extremely important,” Relman added.

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