Expertise in biosynthesis of natural products helps shed light on how microbiota protect the human gut

The School of Chemistry’s Professor Dominic Campopiano is co-corresponding author on a new publication which reveals the molecular basis for how good bacteria provide protection from pathogens in the gut of the worm Caenorhabditis elegans – a valuable model for the process in the mammalian gut which could open up therapeutic options for humans. The paper is out now in Nature Communications.

Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. This new study from an interdisciplinary team, led by Dr Katja Dierking (Evolutionary Ecology and Genetics research group at Kiel University, Germany) with collaborators in China and Edinburgh, addresses this knowledge gap with the soil-dwelling worm C. elegans and its microbiota isolate Pseudomonas fluorescens MYb115 that is known to protect against lethal Bacillus thuringiensis (Bt) infection.

Understanding microbiota-host interactions at the level of the molecular mechanism requires the identification of individual microbiota-derived molecules and their associated biological activities that mediate the interaction. The study reveals the essential role of sphingolipids produced by the good bacteria in host protection against pathogens.

The Campopiano group are experts in how bacteria, mammals and yeast produce sphingolipids, which are essential components of the cell membrane and also play important roles in regulation and metabolism. By exploring the chemical mechanism of the complex, enzyme-driven biosynthetic pathway, their work allows them to explore the molecular basis of the production of these essential molecules.

Figure from the Nature Communications paper showing the proposed biosynthesis from the Campopiano Group's work.
The proposed biosynthesis from the Campopiano Group's work.
Paper co-authors Michael Herrera and Francesca Lubbock
Paper co-authors PDRA Michael Herrera and BSc Hons Biochemistry project student Francesca Lubbock.

The study’s success in unravelling the function of the genes that make sphingolipids opens up the possibility of genetic analysis and identification of other bacteria that could play similar roles, setting up a huge range of further hypotheses to explore how gut microbiota protect against pathogens, and ultimately the potential for therapeutic applications in humans and other mammals.

Dr Michael Herrera, a BBSRC-funded PDRA in the Campopiano group and sphingolipid expert, is a co-author on the paper. The work is also remarkable in being co-authored by an undergraduate BSc Hons Biochemistry project student, Francesca Lubbock, who contributed to the research while carrying out her fourth year project in the Campopiano lab.

It is exciting to be authors on this important, breakthrough paper. We are pleased that our expertise in bacterial sphingolipid research has helped discover a new role in the worm microbiome for these enigmatic lipids.