Bioinformatic approaches for comprehensive study of the microbiome

Abstract

Microbes play essential roles in ecosystems and influence human health both directly and indirectly. To investigate the microbial composition and genetic diversity of human-related environments in high resolution, reveal the underlying functional mechanisms for both detrimental and beneficial microbial groups and evaluate the longitudinal dynamics of microorganisms under different environmental pressures, I performed a comprehensive study of the microbiome in different sources ranging from human-associated marine environments to human gut ecosystems using bioinformatic approaches. Firstly, we tested the hypothesis that benthic microbial diversity and function varies along a pollution gradient, with a focus on human pathogens and antibiotic resistance genes. Metagenomic analysis was conducted including taxonomic investigation, functional detection and ARG annotation of marine sediment samples from four field sites in Tolo Harbour where share increasing degrees of eutrophication. The results suggested a correlation between the marine sediment microbiome and a panel of different pollutant parameters and provided insight into the role of high-turnover microbial communities as well as potential pathogenic organisms as real-time indicators of water quality. Moreover, the inner functional shifts were proved to be contributed by the microcommunities. Together with this marine sediment study, we provided a supplementary analysis in the scale of ecology, aiming to test the hypothesis that eutrophication accelerates decomposition rates, increases abundance of sulfate reducing microbes and reduces carbon storage capacity. Secondly, whereas numerous studies have investigated the role of gut bacteria, the contribution of fungi in health homeostasis is still in its infancy. Hence, we provided the first data to investigate both the bacterial and fungal communities of the lower human gastrointestinal tract over three months after antibiotic treatment concomitantly. The initial results provided an overview of how the mycobiome and its interactions with the bacterial microbiome change and revealed dependencies of specific fungal species from bacterial functions at both DNA and RNA levels which could demonstrate that antibacterial drugs have long-term influence on the human gut mycobiome. The pivotal role of gut microbiota in the development of obesity has been widely recognized. For further exploring the influence of gut microbes on human health, I focused in my third study on whether also visceral fat is correlated with gut microbiome since the accumulation of visceral fat significantly increased the risks of multiple diseases. Therefore, we characterized the gut microbiome in obese patients, healthy subjects and subjects after receiving laparoscopic sleeve gastrectomy for investigating the relationships between the gut microbiome and visceral fat accumulation in a cross-sectional cohort and further exploring the changes of the visceral fat-associated bacteria species in a longitudinal cohort after weight loss intervention. Last but not least, two on-going projects were included in my thesis and consist of a metagenomic study of patients with different levels of NAFLD and another study for investigating microbiomes stability and identifying keystone species responsible for the resistance towards microbiome-based therapeutic interventions. All the aforementioned projects have shown the importance and great value of integrating microbiome studies with bioinformatic approaches when investigating the human-related microbiome in variety of ecosystems.