Assuring growth promotion is a challenge in some places and for some children. While stunting has declined over the past two decades, its prevalence remains alarming, affecting 25% of children under 5 worldwide. Some of the consequences for children include a greater risk of dying from common infections, hindering expected weight gain and linear growth in healthy young children, and dampening immune responses.
Although undernutrition rates have improved since management was decentralized from hospitals to primary healthcare centers and ready-to-use therapeutic food (RUTF) was introduced in the 1990s, children receiving a diet rich in calories but poor in nutrients still struggle to grow.
Childhood malnutrition is also accompanied by gut microbiota immaturity. Indeed, severely malnourished children often lack the gut commensals needed for the gut microbiota to undergo proper development in the first three years of life. As such, scientists have attempted to use specific diets to nurture the microbiota into a mature post-weaning state that might support a child’s growth, with scientists working in Bangladesh reporting that children do not acquire the required gut commensals even when fed nutrition-dense therapeutic foods.
In a paper published in The New England Journal of Medicine, a team led by Tahmeed Ahmed and Jeffrey I. Gordon found that bacteria in the small intestine may activate a pro-inflammatory response that prevents children from getting the calories and nutrients they need.
The origins of stunting may be varied. For instance, environmental enteropathy (also called environmental enteric dysfunction or EED) is a subclinical syndrome first described in the 1960s that is one of the causative factors linked to stunting. The condition dampens the small intestine’s capacity to absorb nutrients, which suggests a potential relationship between the small intestine’s gut microbiota, EED and stunting.
To explore that connection, the researchers recruited 525 children from an urban district in Dhaka, Bangladesh, aged around 18 months old, who were at a high risk of stunting. After a 3-month nutritional intervention, an esophagogastroduodenoscopy was performed on 80 children with EED who had failed to gain weight or show any growth in order to obtain duodenal biopsy samples. An analysis of non-responder undernourished children revealed that small intestine contents in most showed signs of inflammation and shared a core group of the same types of bacteria. Although no classic enteropathogens were found, the greater the number of those bacteria strains present, the worse the stunting.
A set of 10 correlations were found between 14 core bacterial taxa in children with EED and duodenal inflammatory proteins. The bacteria that showed the strongest correlation with duodenal inflammatory proteins were a Veillonella species, a Streptococcus species and Rothia mucilaginosa. However, children with higher levels of intestinal inflammation did not experience more stunting, which highlights that other factors beyond the small intestine microbiome may be behind the pathogenesis of enteropathy.
When a subset of 39 bacteria strains from duodenal aspirates was transferred into germ-free mice, researchers observed an inflammatory infiltrate in the lamina propria and crypt distortion in the animals’ small intestine, which mirrored the inflammatory response seen in children with signs of stunting.
The fact that, for ethical reasons, the researchers did not perform a biopsy on the small intestine of the children who recovered from malnutrition through diet makes it difficult to conclude if absent or present gut microbes in the small intestine are the main contributors to driving the innate immune response. As such, small intestine microbiome analysis via high-throughput molecular approaches—instead of using traditional duodenal culture—is also worth exploring in the context of functional gastrointestinal symptoms.
On the whole, this study opens the door to targeting not only human cells, but especially gut microbial cells in the small intestine as means of improving the health of children who are showing signs of stunting. In that regard, intervention nutrition studies exploring the extent to which therapeutic diets and/or the addition of a sort of bacterial soup may help achieve durable repair of microbiota immaturity in undernourished children might someday help improve the health of malnourished children.
Chen RY, Kung VL, Das S, et al. Duodenal microbiota in stunted undernourished children with enteropathy. N Engl J Med. 2020; 383(4):321-333. doi: 10.1056/NEJMoa1916004.