Category: Systematic

The following is an excerpt from “Systematic: How Systems Biology is Transforming Modern Medicine,” a new book out February 7th. You can pick up a copy on Amazon, Barnes and Noble, or IndieBound or at your favorite book store.

Collecting fecal samples presumably wasn’t anyone’s idea of a fun time, but a team of scientists from Washington University in St. Louis and the University of Malawi had a job to do. The researchers were taking samples from Malawian children because they hoped that the data they could glean from testing the samples held the key to understanding kwashiorkor, a devastating type of malnutrition. Malnutrition is a huge problem in Malawi—about half of Malawian children under five experience stunted growth from inadequate nutrition—but the magnitude of the problem likely wasn’t the only reason the team was working on this issue. It also seemed that kwashiorkor was a type of malnutrition that was affected by more than just what the child ate.

The scientists were studying hundreds of pairs of Malawian twins, and these children displayed an odd pattern. In almost half of the pairs of twins, one twin was malnourished and one was healthy. This seemed strange; after all, identical twins have almost exactly the same genes, and fraternal twins are genetically very similar. When they also are raised by the same parents, live in the same house, and eat the same food, many of the typical environmental and genetic variables that substantially impact a child’s health are very similar for both twins. When all of these risk factors are the same, you would probably expect that both twins would be healthy, or both would be unhealthy. So what was going on?

Maybe kwashiorkor isn’t only about how much food you get, but also about how well you use that food. If both twins are eating the same things, but the healthy twin is simply able to extract more nutrients from that food than her sister is, then that would explain the discordance. The scientists suspected that the efficiency with which these children were able to extract nutrition from their food might be influenced by the types of bacteria living in each child’s gut. If a child has bacteria that allow her to efficiently extract nutrients from her food, the thinking goes, she can stay healthy on a diet that would lead to malnutrition in someone with “inefficient” bacteria.

To study this problem, the researchers first gave all of the children an energy-rich paste known as ready-to-use therapeutic food, or RUTF, and monitored how they responded to the treatment. At first, they did well: they gained weight, became healthier, and the bacteria in their guts perked up immediately. The microbiomes of the malnourished twins started to exhibit signs of metabolic activity that are generally associated with healthy children and “efficient” bacteria. Everything was going well… until the RUTF was stopped. When the researchers finished treating the twins with supplemental food, each child returned to his previous state of either malnutrition or general health, and his bacteria also settled back into their old patterns. The children couldn’t be cured for the long term with RUTF; they improved only while they were getting this energy-rich food.

But what about those bacteria? They seemed to be associated with the children’s health, but that doesn’t necessarily mean the bacteria were involved in causing the malnutrition—they might just be a symptom. So the scientists wanted to know: Were those bacteria actually part of the problem? To find out, the team needed some poop.

Before starting the twins in their study on RUTF, the scientists had taken stool samples from each of the children to understand what bacteria were living in them. About 60% of the dry mass of your feces is actually bacteria from your gut, so this was an effective way of getting at the microbes that the children were carrying. The scientists then took these stool samples and used them to inoculate mice that didn’t have any microbes in their own guts; that way, the scientists knew that whatever microbes grew inside these mice came from the Malawian children.

Once the transplanted bacteria had taken hold in the mice, the researchers fed them food that was intended to mimic the typical Malawian diet, and they watched to see if the mice would develop malnutrition. The animals who got bacteria from the malnourished twins became malnourished, and the mice who got bacteria from the healthy twins remained healthy—even though both groups were eating the same amount of food! And recent work has shown that introducing certain species of bacteria into the guts of the malnourished mice can prevent the growth impairment they would other- wise experience. At least in mice, it seems that the particular types of bacteria that live in the gut can actually be one of the factors that causes these developmental consequences. And as scientists are learning, it turns out that these tiny microbes affect a lot more than just malnutrition.

Most people are already used to thinking of parts of the human body as systems, such as the nervous system, the cardiovascular system, or the immune system. However, there’s one important system that few people know about, a system that accounts for about half of the cells that actually make up the body. It’s the part of the human body that isn’t human.

A typical adult person is composed of about 40 trillion cells, but he or she is host to at least that many microbes living on and in the body. These microbes are mostly bacteria, but there are also plenty of less-familiar single-celled organisms. All told, these microbes make up about three or four pounds of a typical person’s weight. Most of them live in the colon
and digestive tract, though they also inhabit the skin, ear canal, lungs, and any other space where they can find a hospitable environment. These creatures are constantly growing and living and fighting and dying within us, and most of us have no idea.

Want to learn more about how this and other biological systems impact our lives? Pick up a copy of “Systematic: How Systems Biology is Transforming Modern Medicine” starting on February 7th.