Correlation of P-glycoprotein Polymorphisms With Microbial Metabolites in Patients With Alzheimer's Disease (AD) on Medication

The importance of the proposed study concerns the understanding of the way in which each drug acts in each organism separately, both at the genome level and at the microbiome level. It is often observed that various treatments do not have the expected results in all patients, while, at the same time, new pathophysiological mechanisms for each disease are found. The involvement of the intestinal microbiome is one of these mechanisms and as it affects not only the progression of the disease but also the way in which drugs are metabolized (hence their action) should now be considered in every possible case. This led to the emergence of a new field of study related to personalized medicine, pharmacomicrobiomics. It includes microbiology, genomics, and pharmacology, and studies the changes that the human microbiome shows in drug exposure, action, and toxicity. However, this field is relatively new, and although there have been several reports of microbial biotransformation, there has been little in-depth research into the specificity of bacterial strains or the factors that can predict drug transformations. Therefore, this study will give the impetus for the individualized treatment, which will not only concern the genome (which is constantly evolving in recent years) but also the intestinal microbiome, which as mentioned above, is involved in many pathological conditions.

Importance of the study

Although a considerable number of studies have focused on the relationship between the microbiome and the pathogenesis of Alzheimer's Disease (AD), we have not seen any studies on the effect of drugs currently used in the treatment of AD (which are primarily cholinesterase inhibitors), such as rivastigmine, galantamine and donepezil and the NMDA (N-methyl-D-aspartate) glutamate receptor antagonist (memantine). There is also no reference to the composition and / or activity of the microbiome or to the effect of the latter on the pharmacokinetics and / or pharmacodynamics of these drugs. Also, although the human microbiome is influenced by genetic factors in the body, the effect of polymorphisms on the P-gp gene, which is involved in the pathophysiology of AD, the microbiome or its metabolites, has not been studied.