Microbiome & Neurological Disorders
Impact of a Psychobiotic Composition on Mood, Behaviour and the Gut-brain Axis: What have we Learned from 15 years of Clinical Intervention?
While the concept is quite old, dating back to the early 20 th century, the controlled application of microbes to behaviour modification is a relatively new field having less than 20 years of clinical experience. This presentation will outline our path of discovery from our earliest clinical studies in mildly stressed individuals and how this quickly led to studies in major depressive disorder. Along this path we were able to ascertain the differences in doses required for sub-clinical versus clinical
depression. Treatment-naïve participants responded better to the psychobiotics than treatment-resistant patients. In addition, by monitoring a broad range of biochemical compounds, we gained an appreciation of the factors, such as cortisol and brain-derived neurotrophic factor that were modulated by the psychobiotic composition. These biochemical changes were predicted by animal modelling experiments. At the same time we observed a corresponding impact on negative sensations associated with low mood and/or anxiety such as nausea, bloating, abdominal pain, reduced appetite and poor sleep. However, the multifactorial external influences like diet and social interactions in study participants remain uncontrollable, and many questions on timing of intervention and expected outcomes are still unanswered.
Microbes and Migraines: From Mechanisms to Management
Compelling evidence suggests that the human gastrointestinal microbiome impacts, to at least some degree, on the physiology of every organ system in the body. Perhaps the most intriguing is the brain, and the fascinating research in the microbiome-gut-brain axis. Interventions targeting the gastrointestinal microbiome have shown promising preliminary results in a number of neurological diagnoses, such as migraine headache; a common and disabling neurological condition with a complex aetiology. This presentation will explore relevant bacterial-host relationships and human clinical evidence utilising live bacterial therapies for migraine headache.
Parkinson’s Disease: No Guts no Glory
The recently reported leaky gut, intestinal inflammation and changes in the composition of the microbiota in patients point to the relevance of gut-microbiome-immune-brain axis in Parkinson’s disease. Based on (pre)clinical data the talk will shed some light on the possible mechanism of the crosstalk between gut and brain in Parkinson’s disease. There is a great need for additional therapies for Parkinson’s disease that reduce both motor and non-motor symptoms. A poor gut function leads to
a poor brain function and vice versa; therefor targeting the microbiota/gut-immune axis with nutritional interventions or pharmaceutical compounds could be a new approach for the (additional) therapy of neurodegenerative disorders for the treatment of both motor and non-motor dysfunction.
Hype or Reality: Does our Gut Control our Mind?
The impact of our microbiome on our health has gained increasing attention. Recently, strong evidence suggests that bacteria, including commensal, probiotic, and pathogenic bacteria, in the gastrointestinal tract also influence our central nervous system (CNS) signaling systems. In our lab, we investigate whether and how gastrointestinal inflammation and the presence of specific microbiota induce neuroinflammation and inflammation-associated neurological dysfunction. Thereby we mainly focus on one specific CNS barrier, called the blood-cerebrospinal fluid (CSF) barrier, which is located in the choroid plexus tissue in the CSF-filled ventricles of the brain. The blood-CSF barrier is a unique single cell layer that consists of choroid plexus epithelial cells that form an interface between fenestrated capillaries and CSF. In our recent study, we showed that gastrointestinal Helicobacter suis infection in mice results in low-grade systemic inflammation induced by increased gastrointestinal barrier permeability. Consequently, this systemic inflammation has a negative impact on the blood-CSF barrier integrity resulting in increased brain inflammation. Currently, we are studying whether this effect is exclusively occurring upon H. suis infection or also in response to infection with other Helicobacter species. Additionally, it still remains to be determined whether this increased neuroinflammation increases or lowers the sensitivity to neurological disorders such as Alzheimer’s and Parkinson’s disease.
Leveraging the Microbiome-Gut-Brain Axis in Neurological Drug Development
Gut microbes communicate with the brain through various mechanisms:
• Select bacteria are sufficient to mediate seizure protective effects
• Biochemical interactions between bacteria modulate metabolites that regulate brain neurotransmitters
• Data points to leveraging this therapeutic approach to a number of neurological conditions