The IMDEA Food study opens the door to new pharmacological targets of the gut microbiota.

Recent computational analysis developed by the IMDEA Institute of Food Sciences has identified a large number of human and bacterial proteins that are involved in the functioning of the microbiota and many biological processes related to health, such as those related to the immune system, metabolism, nutrition or nervous system. The information obtained from the study will be used to develop new drugs that can modulate their activity through mechanisms that have not yet been studied.

A group of researchers from the Department of Biostatistics and Bioinformatics led by Dr. Gonzalo Colmenarejomade and confirmed predictions of up to 9,700 different interactions between molecules synthesized by gut bacteria – microbial metabolites – and human and bacterial proteins, which have now been published openly for the first time to accelerate the study of the functioning of the gut microbiota and its potential therapeutic use.. This fact is used to develop new therapeutic targets that “imitate” these molecules target areas as diverse as cardiovascular disease, Parkinson’s disease, Alzheimer’s disease, infectious diseases and cancer, with some compounds already in clinical stages.

In recent years, the role that microbiota plays in health has become increasingly relevant. The human body contains trillions of microbial cells, especially in the gut, and many biological processes are influenced by signaling systems established between host cells and the cells of the microbiota itself. This bidirectional communication occurs through metabolites that bind to proteins, thereby causing a biological response.

Based on this work by IMDEA Food, “We were able to identify hitherto unknown patterns that link the structure and chemical class of these compounds, as well as the class and biological origin of proteins.”explains the group’s head, Gonzalo Colmenarejo. Regarding the process carried out, Dr. Colmenarejo details that virtual screening was used to “increase by more than 4 times” set of molecular interactions, validate them by retrospective analysis and prioritize them using bioinformatics tools based on biological significance, and thus “to fill in the gaps that have existed in everything published so far”– he emphasizes.

Fast and targeted experimental testing

The use of these microbial metabolites not only allows for the rational development of new treatments, but also allows the therapeutic target space to be expanded by approximately two orders of magnitude, the size of the enormous microbial genome. The analysis identified 9,711 interactions involving 752 metabolites that were able to bind to 180 microbial and 1,047 human proteins.

In particular, completely new interactions were discovered in 125 combinations of chemical classes. against The protein family is still unknown and has increased in another 326 combinations. This work was published in the Journal of Chemical Information and Modeling, a prestigious journal of the American Chemical Society, and the researchers also contributed to it. Christian Orgaz And Andres Sanchez-Ruiz.

Diagram describing the analysis workflow and tools used in this work.

Thousands of interactions found are now available to researchers around the world so they can be tested quickly and with a high probability of success. “The alternative would be to blindly test all metabolites with all proteins, which would require a lot of time and resources.”says Gonzalo Colmenarejo, who advocates open investigation “because from community centers we can generate fundamental knowledge that, if shared, represents a quantum leap in drug discovery across many therapeutic areas”in this case, for the prevention and treatment of diseases by influencing the intestinal microbiota.