A new study from Baylor College of Medicine and Texas Children’s Hospital explores how bacterial metabolites like isovalerate could bolster intestinal barriers in malnourished children, potentially reducing sepsis risk.
Researchers at Baylor College of Medicine and Texas Children’s Hospital have identified a potential way to strengthen the gut barrier in children with malnutrition, a condition linked to nearly half of deaths in children under 5. The work, published in the Proceedings of the National Academy of Sciences, points to a possible route for reducing the risk of sepsis, a dangerous bloodstream infection that can follow when bacteria escape a weakened intestine.
Geoffrey Preidis, a paediatric gastroenterologist and co-corresponding author of the study, said malnutrition can erode the intestinal barrier, making it easier for microbes to leave the gut and trigger invasive infections. Earlier human research has also shown that malnourished patients tend to have higher intestinal permeability than well-nourished controls, while studies in children have linked poor gut integrity with diarrhoea, sepsis and higher death rates.
In mouse experiments designed to model human malnutrition, the researchers found that the mucus layer protecting the intestine became thinner and the gut more leaky. Live bacteria were able to reach the liver and spleen, but the effect appeared in male mice rather than females, echoing evidence that malnourished boys face a higher risk of sepsis and death. When the same malnutrition model was applied to germ-free mice, which are raised without microbes, the gut barrier problems did not appear, suggesting that the microbiome plays a central role.
The team then focused on bacterial metabolites, the compounds gut microbes produce as they break down food. One group of these compounds, branched-chain fatty acids including isovalerate, was depleted in malnourished mice but present in healthy animals. In lab-grown human colon organoids, miniature versions of the gut, isovalerate appeared to strengthen the barrier by reshaping proteins involved in tight junctions, the structures that help seal cells together. The researchers tested two ways of restoring it in mice: delivering isovalerate directly into the colon and feeding leucine, an amino acid that gut bacteria can convert into isovalerate. Both approaches improved barrier function.
Preidis said leucine could be a practical option because it is inexpensive, does not require refrigeration and is usually well tolerated by mouth. Mary K. Estes, the study’s co-corresponding author, said the human organoid experiments confirmed the mouse findings and offered new insight into how isovalerate helps reinforce the gut lining. The researchers say more work is needed before the approach can be tested in children, but the findings suggest a promising strategy for tackling one of the deadliest complications of severe malnutrition.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
