MetaBiota · Crosstalk between microbiota metabolites and immune cells, the missing link to brain damage.

Crosstalk between microbiota metabolites and immune cells, the missing link to brain damage.

Stroke is a frequent and devastating disease: accounting for almost 1.5 million of people suffering a stroke each year in Europe with only 15% of stroke patients being eligible for a specific treatment. Despite considerable advances in prevention and care, stroke remains one of the most common causes of death and the leading cause of long-term disabilities (Benjamin et al., Circulation 2019). With the ageing population, patients living with stroke are estimated to increase within the next 15 years of almost one million across the EU (Wilkins et al., The Burden of Stroke in Europe, 2017). Thus, there is a pressing need for a better comprehension of the underlying cellular and molecular mechanisms occurring during a stroke to prevent the cascade of deleterious events and to ameliorate recovery. Stroke is a neuroinflammatory disease that is characterized by the recruitment of circulating immune cells to the injured brain. Previous studies have focused on how to modulate the peripheral immune system to improve stroke outcome. The gut contains the largest number of immune cells in our body and immune cell function is regulated by the gut microbiota. Thus, research has recently investigated the critical role of the gut microbiota as immunomodulators and the possible role of the microbiome to influence brain function. Experimental findings suggest that the composition of the microbiota is changing after stroke (also know as dysbiosis) and induces detrimental effects on the ischemic brain. I have shown together with others that the function of immune cells is modulated by the gut microbiota and that intestinal immune cells migrate from the gut to the brain where they contribute to neuroinflammation and secondary brain injury (Benakis et al. Nat. Med. 2016, Singh et al. J. Neurosci. 2016). In particular, modification of the gut microbiota composition towards an anti-inflammatory response in the gut is neuroprotective, and re-establishing the dysbiotic microbiota in mice subjected to stroke by fecal transfer from an non-stroke animal improves outcome, showing a direct connection along the gut-brain axis via intestinal immune cells (Benakis et al., Nat Med 2016; Singh et al., J Neurosci 2016; Sadler et al., Brain Behav Immun 2018). It is still not known which bacterial species and bacterial products are involved in this gut-to-brain communication. Interestingly, gut-to-brain communication may occur via the production of metabolites from the gut resident bacteria. Indeed, there is accumulating evidence showing that metabolites derived from the gut microbiota influence brain diseases via the regulation of intestinal immune cell function. The key objective of my project is to investigate whether metabolites produced by gut bacteria can influence stroke outcome via the regulation of immune cells in the gut.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз