Role of Vitamin B6 on the Microbe-Host Symbiotic Relationship during Ageing

• Applicant: Professor Dr. Filipe Jose Gomes Cabreiro, Ph.D.
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Biogerontology and Geriatric Medicine
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 517786817

Centenarians are the fastest growing age group in western countries. The major burden of disability and ill-health in developed countries falls on older people as advances in technology and other means to maintain people healthier for longer are simply not sufficient. Therefore, this increasingly frail population will have dramatic medical, economic and social costs to a society that is already starting to struggle with coping with an aging demographic. Up to now, research in this area has revealed key factors that regulate organismal ageing mostly from a genetic standpoint. However, ageing is malleable to genetic and environmental interventions. Often, these interventions are performed in well-defined conditions where only one genetic variable is studied at a time, revealing only a minute part of a very complex scenario. Part of the complexity is the interaction of each person with their constantly changing and evolving environment. It has been found that body functions and health are strongly affected by the symbiotic microbes that inhabit the gut. An increasing amount of scientific evidence emerging in recent years has shown the undeniable power of gut microbes to regulate host health, including ageing. However, the understanding of how microbes affect the functions of the host biology is still in its infancy. This is where the use of model organisms such as nematode worms come into play. These models allow us to tease apart the complex interactions between host genetics, gut microbes and nutrition in a way that no other models can. They also provide a platform to prove mechanistic causation between interventions, such as nutrients or drugs, and allow scientists to build mathematical and computational models that can be used for the translation of this information to application in humans. Preliminary studies support the novel idea that bacterial supply of vitamin B6 in the gut can regulate host ageing, consistent with the finding that gut microbes are important providers of varied vitamins in humans. The focus of this proposal is to understand how vitamin B6 modulates host health and lifespan in the context of host genetics, nutritional intake and microbial constitution. The findings of this proposal will inform further projects aiming to use gut microbes in the context of micro and macronutrients to improve late life health.

• DFG Programme: Research Grants