In the current research, I explored the relationship between gut microbiome composition and multiple health outcomes, including obesity, type 2 diabetes, polycystic ovary syndrome and major depressive disorder. I investigated differences in the gut microbiome of individuals with these conditions compared to non-affected controls, while considering lifestyle, dietary, and environmental factors. Data from 7,506 individuals underwent rigorous quality control and harmonisation to define case/control groups and phenotype-specific criteria. Microbiome-wide association analysis was performed using advanced statistical methods MaAsLin2 and ANCOM-BC2 ,in parallel, with adjustments for geographical region, age, gender, and batch effect. The bacterial relative abundance served as the primary outcome measure. 

In this study, I investigated associations between microbiome diversity, bacterial taxa abundance, and health conditions, highlighting the role of short-chain fatty acid-producing bacteria in metabolic and inflammatory pathways. Microbiome variability was characterised both cross-sectionally and longitudinally, revealing dynamic shifts within individuals between different groups and over time. I proposed a method to calculate microbiome risk scores based on the synergistic performance of associated taxa rather than individual taxa, and assessed its potential as a parameter for predicting disease probabilities.

This thesis generated results for four research papers exploring critical aspects of the gut microbiome and its relationship to health. Chapter III presents findings for the first and second papers, which investigate the impact of diet, supplements, and weight on gut microbiome composition, and assess longitudinal changes in gut microbiome composition of 825 individuals, offering valuable insights into within-individual variability over time. The third paper presented in Chapter IV examines the gut microbiome in individuals with a medical history of major depressive disorder, identifying distinct microbial patterns linked to the condition while applying best practices for statistical methods implementation in microbiome research. Chapter V presents data from the fourth paper, which investigates gut microbiome composition and its patterns in individuals with type 2 diabetes and other health complications, and compares them to healthy individuals. These results advance knowledge about microbiome composition in health and diseases.