Childhood undernutrition affects millions of children worldwide and has long-term severe effects, which include stunted growth and impaired cognitive development, among others. A recent study, led by Dr. Jeffrey Gordon from the Centre for Genome Sciences and Systems Biology at Washington University School of Medicine in St. Louis (USA), found that gut bacteria could be considered a useful tool for ameliorating the harmful side effects of malnutrition in mice.
Having defined a model of normal gut microbial community development in Malawian infants and children, Dr. Laura Blanton and colleagues determined that undernourished children exhibited a persistent immaturity of their gut microbiota. To test whether this immaturity of the gut microbiota was a cause rather than an effect of malnutrition, the researchers took faecal samples from 6- and 18-month-old healthy or undernourished Malawian infants and transplanted them into 5-week-old germ-free mice that were fed a Malawian diet – primarily corn flour cooked with vegetables, peanuts and kidney beans. Mouse growth was tracked over the next month. The immature gut microbiota of the stunted and underweight human donors transmitted impaired growth, altered bone morphology, and metabolic abnormalities in the muscle, liver, and brain to recipient mice. Independent of the amount of food consumed, these differences in mouse growth were attributed to the composition of their human-derived microbial communities.
Moreover, mice that had received microbiota from healthy children were allowed to live together with mice that had received microbiota from undernourished children. During the experiments, mice ate each other’s faeces and therefore exchanged gut bacteria. From observing this, the researchers determined that there were beneficial bacteria that could compensate for growth impairments seen in the mice receiving microbial communities from the undernourished children. When adding two of these bacteria, Ruminococcus gnavus and Clostridium symbiosum, directly to ‘unhealthy’ gut microbes and giving this mixture to mice, the growth and metabolic abnormalities were ameliorated. “These results suggest that microbiota may have a role as a cause and also a therapeutic intervention for malnutrition”, says co-author Yue-mei Fan.
These findings show gut microbial communities appear to be a cause of malnutrition in mice, rather than effect, and specific microbes may have a role in directing healthy growth.
In another interesting study from Dr. Jeffrey Gordon’s team, it has been suggested that oligosaccharides in human breast milk may interact with gut microbes in ways that could promote healthy growth and metabolism in undernourished children.
The researchers found that Malawian mothers of healthy infants had significantly higher concentrations of total, sialylated, and fucosylated human milk oligosaccharides (HMOs) than mothers of undernourished infants. As significant amounts of human breast milk were hard to obtain, Charbonneau, et al. studied the effects of sialylated bovine milk oligosaccharides (S-BMOs) rather than HMOs on animal models. To explore the association between S-BMOs and growth in Malawian infants, they colonized young germ-free mice with gut bacteria from a 6-month-old stunted Malawian infant. One group of these mice received a Malawian diet supplemented with S-BMO and a second group received the Malawian diet plus a different kind of sugar commonly added to infant formula, which does not contain sialic acid. A third group received the unsupplemented Malawian diet. S-BMO produced a microbiota-dependent increase in growth by raising lean body mass gain, changing bone morphology, and improving liver, muscle and brain metabolism. The growth promotion effect produced by S-BMO disappeared when it was given to germ-free mice grown under aseptic conditions.
As piglets have physiologic and metabolic properties closer to humans than mice, the researchers reproduced their results in piglets that were born germ-free and colonized with gut microbiota from an undernourished Malawian child.
These experiments indicate a causal and microbiota-dependent relationship between S-BMO and growth promotion.
In conclusion, the team led by Dr. Jeffrey Gordon found that healthy microbes and breast milk oligosaccharides may promote normal infant growth in a microbiota-dependent way. Thus, it is clear that beyond the gastrointestinal tract, gut bacteria may influence the development of distant tissues including muscle, bone, and brain. In the words of Dr. Gordon: “This is just the beginning of a long journey, an effort to understand how healthy grown is related to normal development of the gut microbiota, and how we can establish whether durable repair of microbiota immaturity may provide better clinical outcomes”.
Blanton LV, Charbonneau MR, Salih T, et al. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016; 351(6275):aad3311. doi:10.1126/science.aad3311.
Charbonneau MR, O’Donnell D, Blanton LV, et al. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell. 2016; 164(5):859-71. doi:10.1016/j.cell.2016.01.024.