Dissertation

Alterations of Circulating and Tissue-Associated Microbiome Profiles in the Case of Gastric and Colorectal Cancers

Nikitina, Darja

2024

Overview

Gastrointestinal (GI) tract cancers are considered one of the main public health problems with medical and economic burdens because of their high prevalence and mortality rate. Gastric cancer (GC) is the fourth and colorectal cancer (CRC) is the second most common cause of cancer-related death, with 750,000 and 1.23 million deaths per year, respectively [1–3]. Lithuania is one of the European countries with the highest incidence of GC. The relative prevalence of GC and CRC in Lithuania follows the global trend of being the third and fourth cause of death, respectively [4]. Due to the lack of symptoms in the early stages of both GC and CRC and limited treatment options, the prognosis of GC and CRC remains very poor. Many factors contribute to the development of both diseases, including diet, genetics, environment, and infection with microorganisms [3, 5].Bacteria are one of the most abundant and diverse life forms on the planet. Fossil evidence suggests that bacteria-like ancestors have existed on the Earth for at least 3.5 billion years [6]. Bacteria are ubiquitously present in the environment, air, soil, water, plants, and animals. For a long time, the main focus has been directed to human pathogenic bacteria; however, with time it became known, that bacteria coevolved with humans and are an integral part of human health and perform certain crucial functions.Over the past decade, extensive research has highlighted the important role of the microbiome in several diseases. Although the gut is the main habitat for microorganisms, other body compartments such as the stomach, mouth, respiratory tract, skin, genital tract, liver, and even the eyes are also colonized by microorganisms [7]. The changes in the microbiota composition and/or loss of bacterial diversity (dysbiosis) are the major features of the number of inflammatory and tumorous diseases [8].Studies have shown that some human bacteria may directly promote carcinogenesis or be involved in interactions with the human immune system or oncogenic factors. Studies using animal models have identified specific bacteria, such as Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, and Helicobacter pylori, among others, that are associated with the development of CRC and GC [9, 10]. Knowledge about human health conditions association with bacterial profile changes could be useful for disease risk prediction or microbiome-based therapies [11, 12]. Although H. pyloriis a recognized risk factor for GC, only 1–3% of people with this bacterium develop GC [13].Most research on microbiota has been done using DNA genetic material; however, recent studies are analyzing RNA samples. In order to adopt a common standard for microbiota analysis, there is a lack of comparison between different methods. In addition, there is a lack of studies describing microbiota alterations in precancerous conditions [9].While the tissue and fecal microbiota have received most of the attention concerning various diseases, particularly gastrointestinal diseases, the presence, and significance of microbial genetic signatures in the bloodstream is a novel and intriguing area of research [14]. With the development of technological methods such as next-generation sequencing (NGS), it has been shown that blood contains circulating microbial cell-free DNA – bacterial genetic signatures.

• Publisher: ProQuest Dissertations & Theses
• Subject: Human papillomavirus / Inflammatory bowel disease / Medicine / Mortality / Mutation / Tumors / Virology
• ISBN: 9798346323808