BACKGROUND:
Parkinson’s disease (PD), a progressive neurological disorder1-3 with a multifactorial etiology2,3, is the most common neurodegenerative disease compromising motor functions4,5. Braak et al. have shown evidence of phosphorylated aggregates of a-synuclein in neurons encompassing the enteric nervous system (ENS)6, along the entire gastrointestinal (GI) tract7 in PD. A wide-range of nonmotor symptoms (NMS) are commonly reported as precedents of the motor symptoms by several years8, within which the most commonly reported is GI dysfunction9-11. The increasing body of evidence of an early involvement of the GI tract together with the ENS and hypothetic contribution of environmental factors for the development and progression of PD emerges the interest for a better understanding of interactions happening in the bidirectional gut-brain-axis, known for representing the communication between the GI tract and the central nervous system12-14, without disregarding the key role that the gut microbiota might play12,14,15. As well known, intestinal microbiota composition is sensitive to environmental factors, namely diet and medication16. In turn, such alterations influence host homeostasis, signaling and immune responses17,18. There is been an emerging interest in studying neuroactive-microbial molecules improving brain function and cognition. These neuroprotective metabolites are microbially metabolized and secreted upon the ingestion of prebiotics. Thus, evidencing the potential of a dietary-based intervention as a complementary therapeutic in PD. Thus, a complementary diet-based preventive and therapeutic intervention in PD appears to be essential, since it plays a crucial role in the modulation of gut microbiota composition12,14,19.
RESEARCH PURPOSE AND METHODS:
We have reconstructed the genome-scale metabolic models (GEMs) for the prevalent gut microbiota species reported in patients with PD. Next, we performed a microbial community model using the GEMs to study the microbe-microbe and host-microbe interactions with the host and with integration of distinct dietary plans, namely high protein, high fibre, high fat low carb diets and comprising omnivorous and plant-based restrictions. Based on computational community modelling, we identified the role of individual microorganisms, study their interactions within the community, revealing their potential contribution to disease progression as well as microbial preventive roles. This will enable us to map bacterial-host metabolic interactions in patients with PD. Finally, we will integrate dietary records in order to predict how different macronutrients in food could impact the microbiota community and the host metabolism. Thus, allowing us to understand the impact of diet on gut microbiota modulation and subsequent contribution for PD progression or prevention.

P4-17-06 - Revealing the contribution of distinct dietary plans to host metabolism in Parkinson’sdisease by integrating gut microbial metabolic models