Decoding How Host-Microbiome Communication Impacts Childhood Obesity

Key Words: Childhood obesity, Microbiome, Enteroendocrine cells, Organoids, Single-cell RNA-seq, CRISPR screening

Childhood obesity is a detriment to child health worldwide: the number of afflicted children is rising rapidly, and obesity predisposes children to negative health conditions, including cardiovascular diseases, liver diseases, and asthma, in both childhood and adulthood. To counter this rise, we need to better understand the factors that cause children to become obese and then develop targeted preventive or therapeutic strategies to stop obesity.

This proposal is targeted at understanding a central factor in childhood obesity: the microbes that live in the guts of children, best known as the human microbiome. Over the past years, it has become clear that these microbes shape the risk for obesity, for example by changing how food is absorbed and processed by the body. We currently do not understand how microbes exert these effects. To begin developing this understanding, this proposal addresses the following questions: are there specific microbes that are particularly good or bad when it comes to obesity? What is it about these microbes that make them good or bad? And how do they do this?

By creating an understanding of how the microbiome shapes the risk for childhood obesity, this work may enable us to develop diagnostics to predict which children are most susceptible of becoming obese and non-invasive strategies to prevent children from becoming obese. In addition, this work will improve our broader understanding of how the microbiome influences child health, for example during development of the immune system.