Thesis supervisor: Dóra Szabó
Location of studies (in Hungarian): SE Abbreviation of location of studies: SE
Description of the research topic:
The human microbiota is a collection of microorganisms — bacteria, viruses (including bacteriophages), fungi, and other microorganisms — on the human body surface, mucous membranes, and various human organs. The microbiota is present on the skin, in the vagina, in the oral cavity, but in humans it plays the most significant role in the intestine, especially in the colon, where the gut flora is located. Given that these microorganisms are identified and characterized primarily by their genes, we also use the name microbiome as a synonym for microbiota. 100 trillion (1012) symbiotic microbes live in the human body, 95% of which are found in the gastrointestinal tract. Their genetic material is 150 times larger than the human genome. More than 1,000 different species of microbes have been identified in and around the human body. Typically, most of these species belong to the bacteria Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria phylums.
The human microbiota plays a prominent role in maintaining health, especially in immunity and metabolism. Given the diversity, variability, and complexity of the gut microbiota, interactions between microbial species can play a key role in maintaining and influencing human health. Changes in the composition of the microbiota, various “dysbiosis” in many conditions and diseases, have been described, however, it is difficult to define the characteristic composition of a “healthy” microbiota due to individual variations. The composition of the microbiome is influenced by age, diet, lifestyle, environmental factors, medications, surgeries, and infections. The gut microbiota is made up of the vast majority of bacteria representing more than 1,000 species, but in addition to bacteria, archaea, fungi, and viruses also occur. In healthy people, the two dominant bacterial strains, Bacteroidetes and Firmicutes, and the bacteria that belong to them, make up about 90% of the bacterial community in the gut microbiota. It is characteristic of both strains that the bacterial species belonging to them are only viable under strictly anaerobic conditions. These two strains are primarily responsible for the conversion of dietary fiber to short-chain fatty acids - acetate, propionate and butyrate. In addition to being an energy source for colon enterocytes, butyrate also has anti-inflammatory properties. Actinobacteria and Proteobacteria strains are also present to a small extent in the normal intestinal flora, and the optional anaerobic bacteria confer colonization resistance against pathogenic bacteria, i.e. their presence prevents the pathogen bacteria from adhering and multiplying. Healthy intestinal microbiology is characterized by diversity, a large microbial gene pool, and stable functions.Differences in the composition of the intestinal microbiota can be observed between individuals with demographic, ethnic, gender, age, and different health status, especially at the taxonomic level. Many exogenous factors, such as diet, also affect the current composition of the intestinal flora (microbes), albeit temporarily. The proportion of different bacteria is associated with diet, medication (e.g., antibiotics), and a number of illnesses. For example, the amount of Bacteroides and Ruminococcus species is consistent with an increased intake of food from animal sources, while a plant-based diet favors the proportion of Prevotella.
The following test methods for experimental NGS are used in the study of the human microbiome: shotgun metagenomics sequencing, 16S rRNA sequencing, and metatranscriptomics. Shotgun metagenomic sequencing allows comprehensive examination of all genes in microorganisms present in complex samples. It also allows the detection and analysis of non- or difficult-to-cultivate microorganisms. The procedure allows the detection of bacterial diversity and diversity. Metagenomic studies are often performed by analyzing the sequencing of the prokaryotic 16S ribosome RNA gene. The 16S rRNA contains nine variable regions of approximately 1500 bp in length interrupted by conserved portions. Amplification and sequencing of specific regions of the variable regions of the 16S ribosome RNA gene is used to phylogenetically classify the bacteria present in a given sample. Mycobioma is examined by 18S rRNA analysis of fungi and sequencing by the so-called Internal Transcribed Spacer (ITS). During metatranscriptomics, RNA molecules transcribed from the microbial genome are examined using next generation RNA techniques, which provide important information about the active processes and the host-microbe interaction.
The aim of the PhD topic is to investigate the changes in the microbiome, mainly in the intestinal microbiome, by molecular methods: at the phylum, class, order, and genus level. In addition to determining the bacterial composition of the microbiome, our goal is to determine the fungal composition by determining the mycobioma. Metabolic activity is determined by examining predictive functional metabolism following shotgun sequencing to determine the metabolism of the microbiota and to elucidate the role of the microbiota in various diseases.
Deadline for application: 2024-11-01
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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