Investigating the role of the intestinal microbiota in colorectal cancer development : epidemiological approaches

• Main Author: Zouiouich, Semi
• Other Authors: Centre International de Recherche sur le Cancer, Centre international de recherche sur le cancer, Université de Lyon, Marc Gunter, Inge Huybrechts, Vitaly Smelov
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: HAL CCSD 2021
• Subjects: Epidemiology; Gut microbiota; Colorectal cancer; Epidemiologie; Microbiote intestinal; Cancer colorectal; [SDV.CAN]Life Sciences [q-bio]/Cancer; Northern Finland
• Online Access: https://theses.hal.science/tel-03662440; https://theses.hal.science/tel-03662440/document; https://theses.hal.science/tel-03662440/file/TH2021ZOUIOUICHSEMI.pdf

The gut microbiome is the ensemble of microorganisms that inhabit the gastrointestinal tract. A dynamic host-microbiome symbiosis exists in the intestine and specific interactions between the microbiota and host metabolism and immune system are critical for shaping host physiology. Disturbance of this symbiosis has been hypothesized to play a role in the development of various chronic diseases, including colorectal cancer. Indeed, there is growing experimental evidence that the gut microbiome potentially influences tumor development through dysregulation of host metabolism and immune function. However, epidemiological data linking the gut microbiome with colorectal carcinogenesis remains limited as very few existing cohorts have collected fecal samples. Colorectal cancer screening programs, in which millions of stool samples are collected each year, might provide rich opportunities to establish population-based cohorts with repeated, prospectively collected samples. The first part of the thesis systematically summarizes the current epidemiological literature that has been published in the past decade on the association of the human microbiome with cancer. Our findings emphasised that for most microbiome indicators, the evidence was still too weak to draw firm conclusions in relation to their role in cancer. The second part of the thesis investigates the association between insulin resistance and inflammation - recognised colorectal cancer risk factors - and the gut microbiome in two population-based cohorts – the Northern Finland Birth Cohort and TwinsUK. Our study indicated that higher levels of insulin resistance and other markers of metabolic dysfunction were associated with lower microbiome diversity in both cohorts, even after control for obesity and other factors. Finally, the third part of the thesis evaluates microbiome stability and accuracy in fecal samples collected using different methods employed in ongoing colorectal cancer screening programs. Our findings suggest that commonly used fecal sample ...