In order to understand how the millions of microbes that reside in our guts influence our brain. Our gut and brain are strongly connected and this is known as the gut-brain axis.
Microbiota-gut-brain trialogue is established to be the core of several disorders; inflammatory bowel disorders, obesity, depression, and neurodegenerative diseases, which are rapidly increasing all over the globe. One key regulator of this trialogue is food, which has recently been a topic of interest among the general public because what we feed our body, we also feed our brain and our gut microbes are who digest what we eat (Figure 1).
Our research contributes to finding solutions to these uprising disorders by identifying which gut bacterial metabolites can improve or impair communication with the host gut-brain axis and effectiveness of drug treatment. To make this possible, a close collaboration between microbiology, immunology, (bio)-chemistry and neurology is required.
What we do
We try to find out how gut microbiota sense and metabolise food components that can boost brain chemicals, such as dopamine and serotonin. We then focus on identifying the metabolic products of bacterial break down of these food substances and the enzymes involved. Thereafter, we study possible effects of these newly formed products on the gut-brain axis, which involves the interaction between intestinal immune response and enteric neuronal response with an ultimate effect on the brain (Figure 2).
In parallel, we look into interactions between gut bacteria and medication, which impact the effectiveness of treatment. For example, we recently uncovered that gut microbiota can be a threat for the effectiveness of medication for Parkinson’s patients and this can likely be circumvented by dietary interventions that change our gut microbes (1).
Techniques we apply
We use pure bacterial strains isolated from human gut, co-cultures, and human fecal slurry from healthy subjects and patients to perform fermentation experiments with food components. Through an in-house Liquid chromatography-Mass spectroscopy technique that was recently developed in collaboration with GRIP institute, we identify the bacterial products of their metabolism of food components. We apply classical microbiology and bio-chemistry techniques to characterize bacterial enzymes involved in this metabolism.
To study potential interactions between bacterial metabolites and intestinal neuro-immune response, we employ several in vitro models and stimulate them with bacterial metabolites. Examples of these models include primary epithelial cells (organoids), macrophages, and enteric neurons, in addition to several reporter cell lines that we develop to overexpress receptors of interest. In some cases, we test whether our working model based on in vitro tests are translatable in complex biological environment using in vivo rodent models through close collaboration with GELIFES institute.
1. van Kessel SP, Frye AK., El-Gendy AO, Castejon M, Keshavarzian A, van Dijk GJ, El Aidy S. Gut bacterial tyrosine decarboxylases restrict the bioavailability of levodopa, the primary treatment in Parkinson’s disease. Nature Communications (in press; doi: 10.1038/s41467-019-08294-y).
2. El Aidy S, Stilling R, Dinan TG, Cryan JF. Microbiome to Brain: Unravelling the Multidirectional Axes of Communication. Adv Exp Med Biol. 2016;874:301-36.
Figure 1. Gut bacteria launch complex communication networks with the host immune, metabolic and neuroendocrine systems (2). EEC=enteroendocrine cell, MF =macrophage, ENS= enteric nervous system
Figure 2. Overview of the main research questions