Mining the human gut microbial microproteome for modulators of inflammation

The human microbiome, the bacteria and other microbes that live in and on us, is inextricably interwoven with our health. While these helpful microorganisms were underappreciated for many years, scientists are recently uncovering new links between our microbial selves and a number of diseases and disorders. It’s clear that our immune systems are tightly tuned into the microbiome, but the exact signals that carry that crosstalk from bacteria to human cells are still largely a mystery. Ami Bhatt, M.D., Ph.D., Michael Bassik, Ph.D., and Livnat Jerby, Ph.D., are leading a project to look at the role of the gut microbiome’s micropeptides, tiny proteins that are themselves poorly understood, in human immune health and disease. They will look specifically at how thousands of different microbial micropeptides act on two types of immune cells, macrophages and dendritic cells, both types known to interact with microbiome bacteria as well as harmful bacteria. Their work could lead to new ways of understanding many human diseases, including autoimmune disease, heart disease and cancer.

This project is part of the 2021 Micropeptides and immunity cohort

Our genomes contain vast amounts of DNA that remain poorly understood. A recent arrival on the scene of genomic “dark matter”: micropeptides, tiny proteins coded by tiny genes that had long escaped notice due to their size but that appear to be present in large numbers in our genome and that of every other living thing. These small molecules likely play roles in many different biological processes; scientists are recently uncovering their influence in several different diseases and in the function of the immune system. Scientists in the Micropeptides cohort are shedding new light on how micropeptides influence immunology, in health and in disease.