报告题目: Dynamics of the Human Microbiome
报 告 人：Prof. Rob Knight
Departments of Pediatrics and Computer Science & Engineering, University of California at San Diego
报告题目：Gut microbiota and metabolic diseases: from association to isolation to causation to translation
报 告 人：Prof. Liping Zhao
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University
Abstract for Rob’s talk:
Advances in technology allow us to understand the human microbiota not as a static entity but as a complex, changing ecosystem that records substantial data about our lifestyles, our environmental exposures, and the people we live with. Here I discuss changes in the human microbiota associated with early life events such as delivery mode and antibiotics, the subsequent development of the microbiome throughout life, and even the development of the microbiome after death and its potential utility for forensics. Of particular value for toxicological studies is the ability to transfer the microbiome to germ-free mice, allowing individualized tests of function and subsequent therapies to be tested in personalized rodent models. Relating human to rodent microbiome timescales, especially for dietary studies, and relating multi-omics data in a timeseries context, remain outstanding challenges. Rapid progress is being made in these areas, and will allow far more powerful studies of the effects of drugs in mammalian hosts and our ability to stratify responders from non-responders for a wide range of therapies.
Abstract for Liping’s talk:
Human phenotypes are dictated by the information contents of and molecular crosstalk between the genome and the microbiome. The harmonious integration between human genome and microbiome is the foundation for maintaining a healthy phenome. Poorly balanced diets can turn the gut microbiome from a partner for health to a “pathogen” in chronic diseases. Accumulating evidence supports the new hypothesis that obesity and related metabolic diseases develop because of low-grade, systemic and chronic inflammation induced by endotoxin released into bloodstream from a diet-disrupted gut microbiota. For example, our study showed that an endotoxin-producing bacterium Enterobacter cloacae B29 isolated from the gut of a morbidly obese human volunteer can cause fully developed obesity phenotypes including systemic inflammation, adiposity and insulin resistance when mono-associated with germfree mice. This indicates that specific members of the gut microbiota have the genetic potential to contribute significantly to the development of metabolic disease phenotypes. Thus, the contribution of microbiome to human metabolic phenome must be taken into account when assessing human health. Due to the tight integration of gut microbiota into human global metabolism, molecular profiling of urine metabolites can provide a new window for reflecting physiological functions of gut microbiome. Changes of gut microbiota and urine metabolites can thus be correlated to find out “who des what in the microbiome”. Using this strategy in our recent study on dietary alleviation of human genetic obesity in Prader-Willi Syndrome, we assembled more than 100 high quality draft genomes of prevalent gut bacteria directly from a large metagenomic dataset. Correlation analysis between abundance of these genomes and urine concentration of metabolites identified specific bacteria, which carry the genes for enzymes required to ferment choline into TMA, a precursor of TMAO, a metabolic toxin for inducing atherosclerosis, indicating that these bacteria may contribute to metabolic deteriorations in the hosts. Understanding the contribution of gut microbiota to human metabolic phenome can lead to new insights on mechanisms of chronic diseases such as obesity and diabetes and development of new measures for their management.