Living Microbial Diagnostics to Enable Individualized Child Health Interventions

The microorganisms living inside the human large intestine, collectively known as the gut microbiome, are acquired in the first years of life and shaped over time. They are integral to the health and development of children, contributing to digestion and the development of the immune and central nervous systems. Monitoring the gut’s microbiome composition as well as its associated metabolic environment is critical for child health, as it contributes to detecting the presence of pathogens, inflammation or malnutrition. However, non-invasive methods of monitoring the microbiome composition in the gastrointestinal tract have not yet been developed.

Over the past years, this research consortium has genetically engineered a bacterium to sense, remember and report on the fluctuations in microbiome composition while traversing the animal gastrointestinal tract. Based on the bacterium’s altered gene expression, which varies depending on the presence of metabolites and nutritional factors that it encounters in the gastrointestinal tract, the researchers can discover the nutritional, infection and inflammation state of the gut. For example, changes in iron and zinc levels resulting from dietary modifications can be estimated with this method to an accuracy of 75% and 81% respectively. Yet this bacterium remains blind to changes in vitamin B12, folate or short-chain fatty acids. To further optimize this system, the researchers have also improved the engineered bacterium’s reporting abilities by creating new temperature-inducible recording systems and improving the underlying algorithm analysing the collected data.

In a complementary approach, this consortium aims to understand the impact of malnutrition on the gut microbiome by studying samples collected from mothers and babies living in Zimbabwe and Switzerland. This could help in determining the risk factors for the vertical transmission of an impaired intestinal microbiota from mother to child. The translation of this non-invasive tool into clinical settings will inform clinicians about the nutritional state of children and improve gut microbiome health in breast-feeding mothers and their children.