Analysis of the microbiome of human stool samples : approaching colorectal cancer diagnosis

• Autor(a) principal: Gomes, Carla Filipa Norte
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/25411
• topic: Colorectal cancer biomarkers; Cancer staging; Clinical groups, bacteria, stool, microbiome, dysbiosis, biomarkers, “omics”, metagenomics,16S rRNA gene, clinical diagnosis; Bacteria; Stool; Microbiome; Dysbiosis; Biomarkers; “omics”; Metagenomics; 16S rRNA gene; Clinical diagnosis

Histologically, colorectal cancer (CRC) resides in the abnormal proliferation of epithelial cells of the colon mucosa, progressing from adenoma to adenocarcinoma. This cancer continues to be the third with the highest incidence and mortality worldwide. It is caused by an accumulation of genetic mutations and epigenetic silencing, in addition to other intrinsic and extrinsic risk factors. Due to the high rates of incidence and mortality, diagnostic and prevention tools have been created, implemented, and optimized. However, the need to develop tools that provide an increasingly early, rigorous and sensitive diagnosis remains a pressing need. In this sense, the objectives of this dissertation were: (1) to develop the state of the art about CRC diagnostic tools, (2) to summarize "omic" applications in order to identify microbial biomarkers related to CRC and (3) to compare the microbiome of Portuguese patients with CRC and healthy individuals. Currently, the diagnosis of CRC has been driven by more (e.g., colonoscopy) or less (e.g., imaging techniques, molecular biomarkers) invasive procedures. Recently, the search for microbial biomarkers through "omic" tools has been an alternative, mainly due to the relevance of the microbiome in the metabolic and physiological homeostasis, as well as in the functioning of the host immune system. Thus, the intestinal microbiome has been assigned an active role in the evolution of CRC, being able to influence or be influenced by the disease. In particular, the metagenomic and metabolomic analysis of the CRC-associated microbiome in stool samples has stimulated the scientific community in the search for sensitive, reliable, differential, stable, and early biomarkers in the non-invasive detection of the disease. However, these advances lack representativeness for several geographic areas, given the cultural, genetic, and environmental impact on the incidence of this disease. In this sense, the microbiome (with a focus on Bacteria) was analyzed in feces of two clinical groups constituted by Portuguese individuals (patients with CRC and healthy individuals), through the sequencing of the 16S rRNA gene using Ilumina MiSeq. This study is a contribution to fill the gap of existing knowledge about the microbiome associated with CRC in the Portuguese population. Although the structure of the fecal microbiome assumes homogeneous patterns among individuals of the same clinical group, there was some variability in the abundance of taxa between these groups and at different stages of CRC. For example, Prevotella, Alloprevotella, Sutterella, Desulfovibrio and Olsenella observed in CRC samples can serve as microbial biomarkers. In the future, the study will be extended to larger population samples, as well as to other types of human samples and clinical groups, in order to identify sensitive and specific microbial signatures that can translate the development of CRC, thus reducing incidence rates and mortality.