Unraveling the gut–brain axis

Advances in microbiology, immunology and neurobiology have long hinted at the role bacteria and other microorganisms may have in brain disorders and mental dysfunction. Few organizations, however, have the breadth of expertise to tackle questions at the crossroads of these disparate fields. The Institut Pasteur is an exception and is now embarking on a comprehensive investigation into the inner workings of the gut–brain axis. The Institut Pasteur has established a strategic plan that includes a ‘Grand Programme Fédérateur’ (GPF), or major federating program, that aims to unite forces within the institute’s Paris campus and across the organization’s international network. The goal is to earmark significant resources for studies of the links between microbes (microbiota and pathogens) and neurological diseases so far considered noncommunicable. This will ultimately result in a better understanding of the interactions between the microbes and their human hosts. Since researchers first linked the microbiome to human health over a decade ago, interest in the microbiome and its connection to human biology and disease, including its role in modulating brain function, has exploded. Researchers from the Institut Pasteur’s microbiology, immunology and neurobiology teams have joined forces to better understand the significance of the gut–brain axis in the context of age-related neurological disease. Disorders such as Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, migraine, tensiontype headache and cerebrovascular disease together represent 7% of the total global burden of disease1. To curb the growth in these figures, the research and medical communities must gain a deeper understanding of the factors responsible for neurodegenerative diseases and mental disorders. With this goal in mind, the Institut Pasteur plans to identify internal synergies, promote innovative and translational research and train tomorrow’s leaders in the field.

A four-pronged approach:

The Institut Pasteur’s effort to combine microbiology and immunology with neurobiology makes it uniquely equipped to lead the search for a new understanding of the causes of neurological diseases. Recognizing that in isolation none of these divisions could fully address the breadth of the challenge, the institute developed ad hoc collaborations that led to the establishment of a broader, more formal collaborative effort focusing on four key topics. The first question to be addressed was whether microorganisms can affect brain function through the release of molecules or other mechanisms. The second component was to study how pathogens interfere with brain activity. The third track will focus on developing animal models and related tools to tackle these questions. Finally, the Institut Pasteur plans to translate the outcomes from the above thrusts into clinical approaches to test new treatments for depression, schizophrenia and other psychiatric disorders. The potential of this research raises the prospect of extraordinary advances, such as the ability to reduce the incidence of depressive states by simply altering the microbiome. Other areas where the gut–brain axis could have a role are Parkinson’s disease, obesity and other conditions originally thought of as noncommunicable diseases. The Institut Pasteur is pursuing all of the above as part of its GPF. An international symposium took place in early July 2015 to advance the initiative, and a massive open online course is set to launch in 2016. The Institut Pasteur has also initiated several international academic partnerships around this initiative. Pierre-Marie Lledo, director of the Department of Neuroscience at the Institut Pasteur, explained the significance of the project and what it aims to achieve: “The vision of how the human brain and body work together has continuously evolved over the course of many centuries. Modern neuroscience has now entered a realm of quantitative and holistic methods for measuring how mental states correlate with brain activity and, consequently, how brain activity depends on information relayed from the external world or from our internal state.

Collaborative breakthroughs:

The Institut Pasteur is now looking for partners to help it accelerate the microbiome–brain initiative. Potential collaborators could include industrial partners, nonprofits, venture capitalists and any other party interested in advancing basic findings into the clinic. Currently, the program is supported by a mix of internal funding and external contributions from organizations such as the Fondation Daniel & Nina Carasso, and it will continue expanding as additional partners join. A comprehensive understanding of the microbiome–brain axis is perhaps the biggest unmet need and market opportunity left in healthcare. New partners will be joining a long list of organizations that have recognized the unique combination of capabilities the Institut Pasteur brings to the table to tackle this complex challenge.

Reference 1. Chin, J.H. & Vora, N. The global burden of neurologic diseases. Neurology 83, 349–351 (2014)

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