The holiday season in most developed countries revolves around food, but for people living in the world’s poorest nations, getting enough to eat anytime of the year is an everyday struggle. Those most affected by hunger are children.
The 2016 NIEHS Hans L. Falk Memorial Lecture highlighted the global health challenge of chronic undernutrition in children and the influence that gut bacteria, known as microbiota, have on the condition. This year’s speaker, Jeffrey Gordon, M.D., presented "Childhood Undernutrition and Gut Microbiota Immaturity: Human Development Viewed From a Microbial Perspective." NIEHS Deputy Director Richard Woychik, Ph.D., hosted the Nov. 2 seminar.
Falk was an internationally known cancer researcher and environmental health science leader. He joined NIEHS in 1968 as associate director for laboratory research and later became associate director for health hazard assessment.
The bacterial collective
Gordon said that undernutrition is responsible for more than 3 million deaths a year in children under the age of 5 years. His research, funded by the Bill and Melinda Gates Foundation through the Breast Milk, Gut Microbiome, and Immunity Project, is determining the connections among normal human development and the stunting of growth, neurodevelopmental abnormalities, and the immune dysfunction associated with undernutrition.
"During the past 15 years, there’s been a revolution in treating children with severe, acute malnutrition with the administration of ready-to-use therapeutic foods," Gordon said. "Although mortality has been reduced, the long-term health problems that persist in these children are not overcome with current treatment regimens. We want to know the factors that conspire to produce this disabling disorder that robs children of their ability to reach their full potential."
Of the tens of trillions of organisms that live on and in the human body, the largest collection exists in the gut. Gordon urged members of the audience to think of this microbial community as an indispensable organ that transforms the ingredients in human diets into metabolic products that benefit not only the microbes, but us.
Before examining how undernutrition negatively affects a child’s development, Gordon and his colleagues had to understand how the gut’s microbial community develops in healthy children. The researchers turned to a cohort of children born in an urban slum in Mirpur, a district in the city of Dhaka, Bangladesh. Each month during a child’s first two years of life, the team collected fecal samples and measured the height and weight of healthy children.
Using fecal samples collected from children that exhibited healthy growth, they sequenced the 16S RNA gene, a gene present in all bacteria, to determine what microbes were part of the gut communities. Applying machine learning tools to the data sets, the researchers identified 24 of the most age-discriminatory strains. Many of the same 24 strains turned up in other healthy birth cohorts from around the world. By noting the relative proportions of these microbes in a child’s gut, Gordon and his team could assign an age or state of development to that child’s microbiota.
Gordon said when this microbial signature was applied to undernourished children, they discovered that their gut microbiota was younger, or more immature, than that expected based on their chronological ages.
"One 18-month old child was admitted to the hospital suffering from severe, acute malnutrition, and his microbiota resembled that of a 9-month-old," Gordon said.
Battle of the microbiota
Gordon and his students transplanted immature microbiota from undernourished children living in Malawi, or normally maturing microbiota from their chronologically age-matched healthy counterparts, into young germ-free mice. They found that the mice that received the microbiota from underweight, stunted donors exhibited impaired growth and metabolic abnormalities compared with mice that received microbiota from healthy donors.
Another study placed germ-free mice, which had received either healthy or undernourished human microbiota in the same cage. Surprisingly, the undernourished mice did not experience abnormal growth. Gordon’s students found that bacteria from mice carrying healthy microbiota invaded the microbiota of mice carrying undernourished microbiota. This finding suggests microbiota immaturity is related to malnutrition.
Woychik summed up the theme of the talk by saying, "If you want to stay healthy, pay attention to the bacteria in your gut."