Malnutrition, and a Battle of the Microbiota
Is malnutrition due to more than just a lack of access to quality food? In work published this week in the journal Science, researchers first collected fecal samples from 6- and 18-month-old children in Malawi. Then, they transplanted those samples into mice fed a typical human Malawian diet. Mice that received samples from healthy children grew and developed better than those that received samples from malnourished children. They also found that the effects were somewhat contagious—a mouse that received one fecal transplant could pass on the associated microorganisms, and their health effects, to germ-free mice housed in the same cage. Jeffrey Gordon, one of the authors of the paper, says the work indicates that a “battle of the microbiota” taking place in the gut may play a significant role in health.
Jeffrey Gordon is a microbiologist and director of the Center of Genome Sciences and Systems Biology at Washington University School of Medicine in St. Louis, Missouri.
IRA FLATOW: The World Health Organization says that malnutrition is a contributing factor in more than one third of all child deaths worldwide, and lack of access to safe and healthy food is certainly a major part of malnutrition. But research out this week in the journal Science says that food access may not be the only player. There may be a role for the microbiome– what else?– as well. Jeffrey Gordon is a professor at Washington University School of Medicine in Saint Louis and one of the authors on that paper. Welcome to Science Friday.
JEFFREY GORDON: So nice to be here.
IRA FLATOW: Thank you. Walk us through how you know that the microbiome plays a role in malnutrition.
JEFFREY GORDON: Well, let’s go back to some studies about what we can do with malnutrition and what we have been able to do. We know that this set of disorders is not due to food insecurity alone, as you pointed out. We also know that there’s been a dramatic advance in reducing mortality with the treatment of children, particularly with severe malnutrition with these so-called ready to use therapeutic foods. And although mortality is reduced, some of the long-term consequences of malnutrition– persistent stunting, neuro-developmental abnormalities, impaired immune responses, including to vaccinations– those haven’t really been effectively treated.
So we’re missing something. And what might that be? Most of us think about human development from the perspective of our human cells and organs. We were curious to think about another dimension to our development, and that involves our microbial communities, particularly the largest such community that lives inside of us, our gut microbiota. Two years ago, we studied a group of children, members of a birth cohort living in Bangladesh, a group that had healthy growth, and those that developed severe under-nutrition.
And what we found was there is a program of development of this microbial organ that occurs in healthy individuals that can be characterized by the appearance and relative representation of a group of bacterial strains. And that provides a measurement tool to see whether this organ is developing normally in children with malnutrition. What was found then, in that cohort of children, was that those who have severe acute malnutrition have impaired development of this organ. They have a microbial community that appears younger than what you would expect based on their chronological ages.
Equally importantly, when these children are treated with these ready to use therapeutic foods, there is a partial, but only transient, improvement in this immaturity. So what happens is that these children have a persistent developmental abnormality affecting this organ. We ask, could this be a causal factor in malnutrition or was it simply an effect of malnutrition? And what could we do to repair this immaturity and what effect might it be on healthy growth?
IRA FLATOW: I’m Ira Flatow, this is Science Friday from PRI, Public Radio International. I’m talking with Jeffrey Gordon. So you found direct evidence that there is a connection between a malnourished child and an unhealthy microbiome?
JEFFREY GORDON: Well, we made those observations about immaturity of the gut microbiota in Bangladesh. So we traveled from South Asia to East Africa, to Malawi, and asked a couple of questions. First, is this program of normal development, the microbiota, shared across populations that have very different cultural and culinary traditions? And this would be in healthy children. And the answer was yes. Same features, many of the same features, in terms of which microbes were appearing when during the first couple of years of life were evident in healthy Malawian children, just as they were unhealthy Bangladeshi children. And as in Bangladesh, we saw that children who were malnourished had impaired development, this microbiota immaturity.
But, again, the question is, effect or cause? So a very talented graduate student in the lab rolled up her sleeves and did a series of organ transplants. In this case, the organ is a microbial organ. And the transplants involve taking a microbial community from children, from Malawi, who had healthy growth, and children who are severely stunted and under weight. She took these communities and implanted them into the guts of mice that have been reared under sterile conditions, who are fed a diet similar to those consumed by the children in Malawi.
When she transplanted healthy communities that were maturing normally, the animals grew very well. Muscle mass increase, bone growth, metabolism, in multiple organs. And those microbial communities were from stunted underweight children, and they had this immaturity. The recipient mice had growth faltering even though all groups of mice were consuming the same amount of this Malawian diet. So the same food, the same amount, but a different microbial community.
IRA FLATOW: Well, how hard would it be to try this out in children. I mean you’re not feeding them anything, you know? I understand from the research that just the mice being around the other mice had, sort of, transferred the good bacteria to them.
JEFFREY GORDON: Well, what are the actors that we want to feed? can we focus our attention on those organisms that are actually the agents that promote growth? And that was another important part of this story. So a variety of different methods were used to find a group of these age discriminatory organisms that form part of the signature by which we judge the development of this microbial organ, and identifies–
IRA FLATOW: I’m running out of time so I have to ask you, did you identify something and could you use it?
JEFFREY GORDON: Yes. We did identify them and they become the targets of new types of foods that will sponsor their adequate representation and expression of the functions that they need to express that promote growth.
IRA FLATOW: And are you going to try it out on the kids?
JEFFREY GORDON: Yes we’re moving forward in the coming years to test this new type of microbiota directed foods that are directed at these organisms that we think are instrumental in promoting healthy growth.
IRA FLATOW: One last quick question. What strain of bacteria did you identify?
JEFFREY GORDON: It’s not just one. There are an ensemble of these organisms that are important.
IRA FLATOW: We’ll have to pick this up because we’ve run out of time. But it’s interesting. Another microbiome success. Jeffrey Gordon, professor at Washington University School of Medicine in Saint Louis