Studying microbial communities through next generation sequencing

Abstract

Human microbiome is an emerging target of study, with its significance lying on the clinical aspect. This thesis focuses on examining the potential impacts of the microbiome on human health with four independent pieces of research. We applied shotgun metagenomic sequencing method to study microbial communities that are deeply related to human health. First, we demonstrated that the banknotes are the potential carrier of pathogen and antibiotic resistance genes by analyzing the microbiome on the surfaces of Hong Kong Dollar banknotes by comparing its microbiome data with that of Indian Rupee banknotes, and other environmental samples collected in Hong Kong. Second, to assess the direct impact of antibiotics by oral administration on the gut microbiome, we analyzed the longitudinal gut microbiome of healthy human by integrating the metagenome and metatranscriptome data. Bactericidal antibiotics perturb the community structure more dramatically, whereas bacteriostatic antibiotics may cause a long-term decrease in community diversity after treatment. Third, to demonstrate the impact of the gut microbiome on human health, we analyzed the gut microbiota of cancer patients, and identified some gut-specific, bacterial-species influence on anti-cancer treatment outcome through metagenomic analysis on patients’ stool samples. The results of this analysis were validated both in vivo and in vitro. The identified biomarkers were further used to build a classification model to predict the treatment outcome. This substantial finding motivated us for further investigation on the involvement of gut microbiota in cancer patients, so we assessed the association between the gut microbiome and cancer cachexia, specifically in lung cancer patients, by integrating the two omics data: the gut microbiome and the plasma metabolome data. Remarkably, both omics data consistently demonstrated the significance of branched-chain amino acids (BCAAs) in cachexia of cancer patients. All listed studies have shown a significant role of the human-associated microbiome in human health.