Understanding the impact of the microbiome on growing children

An international team of researchers studied the microbiome of children in low- and middle-income countries in Asia, Africa and South America and found that no single genus was associated with stunting, though some correlations could be made with an abundance of opportunistic microbes that could increase inflammation.

“While there is growing interest in understanding the gut microbiome’s role in childhood stunting, current research remains limited,” they wrote. “In this review we show both inconsistent and consistent changes in microbial composition across different studies between stunted and non-stunted children.”

Factors influencing stunting​

According to the World Health Organization, stunting—which is height for age more than two standard deviations below the typical child growth median—impacted over 148 million children under the age of five in 2022. Caused by lack of nutrition and ongoing infections, stunting is primarily found in Africa and South Asia, where approximately 50% of all stunted children live, the researchers cited.

"As the population in low- and middle-income countries continues to grow, the number of children affected by stunting will likely increase," they wrote. "Stunting has a range of adverse outcomes, including increased susceptibility, incidence and severity of infectious diseases (particularly pneumonia and diarrhea), poor cognitive development and mortality."

There are many factors that may influence stunting such as poor sanitation, recurrent infections, poor nutrition and genetic predisposition. The review suggests additional studies have shown the gut microbiome role in childhood growth and that changes in the gut microbiome composition are connected to stunting.

“The gut microbiome, a complex community of bacteria, eukaryotic and prokaryotic viruses, fungi and archaea in the gastrointestinal tract, has a range of functions relevant to normal childhood growth and development,” the researchers wrote.

These include the metabolism of nutrients, creation of vitamins for growth and maintaining gut health. Hormone regulation is also part of the microbiome as well as energy harvesting from nutrients and sustaining the intestinal mucosa’s structure and barrier function. Additionally, the gut microbiome helps to develop the innate and adaptive immune system and provides protection against pathogens and infections.

"The colonization of the intestinal microbiome overlaps with critical developmental periods of child growth," the review noted. "Young children, particularly in LMICs, are at high risk for microbiota perturbation secondary to frequent infectious illness episodes, antibiotic use, poor nutrition and unsanitary living environments. However, how these perturbations and the composition and function of the developing microbiome may translate into growth outcomes and health is uncertain." 

Study details​

The researchers reviewed data from 14 studies that used high throughput genomic sequencing methods to analyze the gut microbiome in stunted and non-stunted children under the age of 5 in the regions affected.

Although the studies generally did not find any significant differences in alpha diversity, higher beta diversity was noted in stunted children in four of the studies.

"No single genus was associated with stunted children across all 14 studies, and some associations were incongruent by specific genera," the researchers wrote. "Nonetheless, stunting was associated with an abundance of pathobionts that could drive inflammation, such as Escherichia/Shigella​ and Campylobacter​, and a reduction of butyrate producers, including Faecalibacterium, Megasphera, Blautia​ and increased Ruminoccoccus​.”

The reviewers assessed the gut microbiome in fecal samples for all studies. In addition to fecal sampling, some of the studies analyzed duodenal and gastric samples. 

The researchers found "an increase in bacteriophage richness with an increase in bacterial richness in children with adequate and moderate growth, which was not observed in children with poor growth."

Gut microbiome immaturity may also be a factor related to stunting.

"The immature microbiome associating with severe malnutrition was characterized by a reduced microbial diversity, a depletion of Faecalibacterium, Bifidobacterium, Clostridium​ and Ruminococcus​, and an increase in pathogenic microorganisms at 18 months," the researchers wrote. "[We] hypothesize that microbiota immaturity can contribute to systemic inflammation, impaired nutrient synthesis and absorption, exacerbating the malnutrition cycle."

The review observed that only Campylobacter​ was reported to be significantly higher in stunted children across the three global regions they studied.

"Understanding the role of the gut microbiome in human health, particularly childhood stunting, has important implications for developing interventions aimed at and improving stunting outcomes," they wrote. "As such, using the gut microbiome to improve health outcomes is a promising area for future research. There is an urgent need for microbiome studies to have clinically relevant results."

The researchers added that more studies using advanced techniques such as metagenomics, metabolomics and transcriptomics could provide more insight into organisms and metabolic pathways in the gut and how they influence growth in children.

Source: Nature​
doi: 10.1038/s41522-024-00517-5​
“Systematic review of associations between gut microbiome composition and stunting in under-five children”
Authors: Mwelwa Chibuye et al.