For millions of young children suffering from severe acute malnutrition, impaired development of the gut microbiome may stop them from fully reaping the benefits of the food they eat (1). Researchers have recently discovered that a population-specific gut bacterial strain may aid children’s recovery from severe acute malnutrition (2).
The bacteria Bifidobacterium infantis are early beneficial colonizers of children’s guts. Without these microbes, pathogenic bacteria can populate the gut in its place, and children may not be able to fully digest food and absorb the nutrients they consume. Past collaborative research by Jeffrey Gordon at Washington University School of Medicine and the International Centre for Diarrhoeal Disease Research (ICDDR) revealed that food-based interventions that encourage growth of B. infantis can be successful in older children with moderate acute malnutrition (3).
For infants whose guts lack B. infantis, however, the bacteria must first be introduced to their bodies. In a new Science Translational Medicine study conducted by the ICDDR and Gordon’s group, researchers sought to treat severe acute malnutrition in Bangladeshi children by introducing B. infantis into their gut microbiomes.
“This is a really strong paper, [and is] very important for a specific group; there're way too many children in the world still who have malnutrition,” said Ardythe Morrow, a pediatric nutrition researcher at Cincinnati Children’s Hospital who was not affiliated with the study. “At the same time, [the paper] also has a larger conceptual contribution, which is understanding that the pairing of the diet, even in infancy, with specific microbial strains can be important and that we have a lot of learning to do to get that right.”
Throughout two decades of prior research, scientists determined that a US-derived strain of B. infantis resolves symptoms of acute malnutrition in infants in the US whose primary diet consists of breast milk. When present in the gut, B. infantis enables digestion of human breast milk oligosaccharides that would otherwise not be processed by the infant (4). However, Bangladeshi children’s diets are often not exclusively comprised of breast milk. Early on, they eat plant-based staples such as rice and lentils.
In this clinical study, the research team treated Bangladeshi children with the US-based B. infantis strain. In response to the treatment, the children showed some weight gain, but the amount of B. infantis in the gut was two orders of magnitude lower in malnourished children than in healthy children. The malnourished children also lost their populations of healthy gut bacteria when the intervention stopped.
In light of these results, the researchers decided to isolate B. infantis strains from fecal samples of healthy infants in Bangladesh to investigate whether these locally derived strains might lead to better outcomes for malnourished Bangladeshi infants. In preclinical in vivo studies, they identified a Bangladeshi strain of B. infantis that promoted weight gain in rat pups that had the same initial gut microbiome makeup as malnourished Bangladeshi infants and that were fed a mixed diet of milk and plant-based foods to mimic local human diets. By sequencing the genome of the Bangladeshi B. infantis strain, they found that in addition to its ability to process nutrients present in breast milk, it also expressed genes involved in processing plant-based nutrients common to Bangladeshi children’s diets.
“There's a tremendous amount of strain-level variation in the human gut microbiota. And that strain level diversity is actually quite important because different strains can perform different functions depending upon the environmental circumstances,” said Gordon. “For probiotic discovery, should we try to adopt the philosophy that perhaps one strain doesn't fit all, and that there are interesting opportunities in mining the microbial communities?”
Going forward, Gordon’s research group and the ICDDR plan to test this newly isolated strain of B. infantis in a clinical population of Bangladeshi infants with severe acute malnutrition to see if it improves the children’s recovery compared to what they saw previously when using the commercially available US strain.
“The microbial world is not a monolith. It’s very diverse, and we have to learn how to deal with that,” said Morrow.
References
- Subramanian, S. et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510, 417–421 (2014).
- Barratt, M.J. et al. Bifidobacterium infantis treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition. Science Transl Med 14, eabk1107 (2022).
- Gehrig, J.R. et al. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science 365, eaau4732 (2019).
- Sela, D.A. Bifidobacterial utilization of human milk oligosaccharides. Int J Food Microbiol 149, 58-64 (2011).
