German Clinical Trials Register

Acronym/abbreviation of the study

MicroMeDi

URL of the study

No Entry

Brief summary in lay language

The human microbiome is defined as the sum of all microorganisms (bacteria, fungi and phages) living in the body or on its surface. Many of these organisms are associated with aspects of health and disease. The gut flora plays a central role in the development of the immune system and the metabolism. In some diseases, e.g. Alzheimer's, it has been shown that the gut flora has an influence on the course of the disease. The communication pathway between the gut flora and the brain is referred to as the "gut-brain axis". The communication arises from the fact that bacteria can also influence processes in the brain via the release or degradation of certain signal substances. It is assumed that one can influence the composition of the gut flora via the daily diet and thus one can also influence the communication via the gut-brain axis and influence some symptoms of a disease. In this study we want to learn more about the microbiome in the gut, skin and saliva of patients with rare monogenic metabolic diseases and compare it with the microbiome of carriers and healthy controls. We want to investigate whether there are differences in the amount and type of microorganisms and metabolites in patients with rare monogenic metabolic diseases compared to carriers and healthy controls. In addition, we want to find starting points for future treatments.

Brief summary in scientific language

Rare monogenetic metabolic diseases are caused by variants in genes encoding proteins involved in metabolic pathways. In general, these defects lead to (1) an accumulation of toxic metabolites as metabolic side reactions are utilized instead, and (2) reduced or absent production of the metabolite, leading to metabolic dead ends. In neurotransmitter defects, patients suffer from neurological phenotypes such as early-onset developmental delay, cognitive deficits, autonomic dysfunction and movement disorders, whereas patients with urea cycle defects show cognitive deterioration due to the accumulation of neurotoxic NH4+ in metabolic decompensation. The human microbiome is defined as the sum of all microorganisms (including bacteria, fungi and viruses) that live inside the body or on its surface. Neurodevelopment is closely linked to the gut microbiome. Accumulating studies point to a complex interplay between the microbiome and aspects of neurodegeneration, as seen in Parkinson's disease, Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. An apparent communication pathway between the gut microbiome and the brain, the so-called "gut-brain axis", is based on the idea that bacteria can produce or consume neurotransmitters such as dopamine, serotonin or GABA. However, research has mainly focused on the microbiome of animals, such as rodents. In recent years, an increasing number of studies have been conducted on the human microbiome. Here, intervention-based approaches using prebiotics, probiotics, fecal transplantation and antibiotics have been used to identify key components of the microbiome that influence neurodevelopment. While this evidence suggests a clear influence of the microbiome on the development and function of the central nervous system, further research is needed. The aim of this study is to characterize the microbiome of patients with rare monogenetic metabolic diseases in order to lay the foundation for the development of future treatment options such as transfection, dietary changes and probiotic approaches to alleviate symptoms.