TY - BOOK

T1 - Metagenomics Study on the Polymorphism of Gut Microbiota and Their Function on Human Health

AU - Feng, Qiang

PY - 2015

Y1 - 2015

N2 - As the key component of the human micro-ecosystem, intestinal microorganismstransfer energies and exchange information with the human body. While they playessential roles in maintaining homeostasis in our bodies, until recently, we have hadvery limited understanding of the extent of taxonomic diversity and functionalcomplexity of the gut microbiome. Facilitated by the Next Generation Sequencing(NGS) technologies and the progress of bioinformatics in the past decade, we haveacquired substantial achievements in metagenomic studies on human gut microbiomeand established the fundamentals of our understanding of the interactions between gutmicrobes and human body, and also the importance of this interaction on humanhealth. As one of the milestones, the first integrated gene catalog in the human gutmicrobiome was constructed in 2010 in the scheme of the Metagenomics of HumanIntestinal Tract (MetaHIT) Project, which was conducted by BGI and other researchinstitutes under the 7th FP program of European Commission. This gene catalogcontains 3.3 million non-redundant reference genes. By estimation, each individualharbors approximately 1,000 to 1,500 microbial species and on average 160 ‘corespecies’ are shared in the population. These microorganisms participate in variousmetabolic pathways and activities of the immune system and the nervous system ofour bodies，and have fundamental impacts on our health. For example, an associationstudy between gut microbiome and type 2 diabetes (T2D) highlighted a series ofmicrobial gene markers possibly related to this disease and among them, 50 markersshowed great potential for diagnosis.Based on previous work, we further collected 1,267 samples of gut metagenomes datafrom 1,070 individuals living in three continents (North America, Europe and Asia)and constructed a 9.9 M non-redundant high-quality gene catalog representing the gutmicrobiome feature of about 5% of populations around the globe. Following the sameprinciple, a 2.6 M gene catalog of the mice gut microbiome was constructed and acanonical animal gut model was built. A comparison to the human gut catalogrevealed that only 4% of the genes were shared by the human counterpart,highlighting the significant difference between these two gut microbiome datasets.To understand the establishing process of gut microbiome during the first year of lifeafter birth, fecal samples from 98 infants and their mothers were collected and analyzed after parturition. In this study, we found that delivery methods (vaginally- orC-section-delivered) and feeding regime (breast-feeding or mixed feeding) hadsignificant impacts on the gut microbiome of the infants.Moreover, metagenome-wide association studies (MGWAS) were conducted toinvestigate the potential relationship between gut microbiome and diseases such ascolorectal adenoma (CRA) and carcinoma (CRC), rheumatoid arthritis (RA) andcoronary heart disease (CHD). Compared to the healthy individuals, CRA and CRCpatients exhibited an enrichment of specificly low abundannce microbes in their gut,which were positively related to the red meat intake, while taxa associated with fruitand vegetable intake were depleted. Abundance changes in certain bacteria, such asFusobacterium nucleatum and Parvimonas micra, were correlated with the differentstages during CRC development. Four genes were selected as reliable markers toidentify CRC patients in Chinese, Danish and Austrian populations, which holdspromising implications in non-invasive diagnosis in the future.In the study of the gut and oral microbiomes abnormalities in RA patients,Haemophilus sp. was found depleted, which was negatively correlated to theconcentration of RA immune antibodies, while Lactobacillus salivarius wassignificantly enriched in the feces, dental plaque and saliva of the RA patients, andwas positively related to the order of severity of the disease.The comparison between the gut microbiome of atherosclerosis CHD patients andhealthy controls showed significant differences between the two groups. Further more,by integratively analyzing the urine metabolites and fecal microbiota, wedemonstrated that gut microbiome dysbiosis was closely correlated with the metabolicabnormality in CHD patients.The extended integrated gene catalog of the human gut microbiome and the followingassociation studies in a series of complex diseases highlight the strong connectionbetween intestinal microorganisms and human health. These studies also shows agreat potential of using microbiome-based approaches for early diagnostics, and alsoin therapy and prevention of common diseases such as T2D, CRC, RA, and CHD.

AB - As the key component of the human micro-ecosystem, intestinal microorganismstransfer energies and exchange information with the human body. While they playessential roles in maintaining homeostasis in our bodies, until recently, we have hadvery limited understanding of the extent of taxonomic diversity and functionalcomplexity of the gut microbiome. Facilitated by the Next Generation Sequencing(NGS) technologies and the progress of bioinformatics in the past decade, we haveacquired substantial achievements in metagenomic studies on human gut microbiomeand established the fundamentals of our understanding of the interactions between gutmicrobes and human body, and also the importance of this interaction on humanhealth. As one of the milestones, the first integrated gene catalog in the human gutmicrobiome was constructed in 2010 in the scheme of the Metagenomics of HumanIntestinal Tract (MetaHIT) Project, which was conducted by BGI and other researchinstitutes under the 7th FP program of European Commission. This gene catalogcontains 3.3 million non-redundant reference genes. By estimation, each individualharbors approximately 1,000 to 1,500 microbial species and on average 160 ‘corespecies’ are shared in the population. These microorganisms participate in variousmetabolic pathways and activities of the immune system and the nervous system ofour bodies，and have fundamental impacts on our health. For example, an associationstudy between gut microbiome and type 2 diabetes (T2D) highlighted a series ofmicrobial gene markers possibly related to this disease and among them, 50 markersshowed great potential for diagnosis.Based on previous work, we further collected 1,267 samples of gut metagenomes datafrom 1,070 individuals living in three continents (North America, Europe and Asia)and constructed a 9.9 M non-redundant high-quality gene catalog representing the gutmicrobiome feature of about 5% of populations around the globe. Following the sameprinciple, a 2.6 M gene catalog of the mice gut microbiome was constructed and acanonical animal gut model was built. A comparison to the human gut catalogrevealed that only 4% of the genes were shared by the human counterpart,highlighting the significant difference between these two gut microbiome datasets.To understand the establishing process of gut microbiome during the first year of lifeafter birth, fecal samples from 98 infants and their mothers were collected and analyzed after parturition. In this study, we found that delivery methods (vaginally- orC-section-delivered) and feeding regime (breast-feeding or mixed feeding) hadsignificant impacts on the gut microbiome of the infants.Moreover, metagenome-wide association studies (MGWAS) were conducted toinvestigate the potential relationship between gut microbiome and diseases such ascolorectal adenoma (CRA) and carcinoma (CRC), rheumatoid arthritis (RA) andcoronary heart disease (CHD). Compared to the healthy individuals, CRA and CRCpatients exhibited an enrichment of specificly low abundannce microbes in their gut,which were positively related to the red meat intake, while taxa associated with fruitand vegetable intake were depleted. Abundance changes in certain bacteria, such asFusobacterium nucleatum and Parvimonas micra, were correlated with the differentstages during CRC development. Four genes were selected as reliable markers toidentify CRC patients in Chinese, Danish and Austrian populations, which holdspromising implications in non-invasive diagnosis in the future.In the study of the gut and oral microbiomes abnormalities in RA patients,Haemophilus sp. was found depleted, which was negatively correlated to theconcentration of RA immune antibodies, while Lactobacillus salivarius wassignificantly enriched in the feces, dental plaque and saliva of the RA patients, andwas positively related to the order of severity of the disease.The comparison between the gut microbiome of atherosclerosis CHD patients andhealthy controls showed significant differences between the two groups. Further more,by integratively analyzing the urine metabolites and fecal microbiota, wedemonstrated that gut microbiome dysbiosis was closely correlated with the metabolicabnormality in CHD patients.The extended integrated gene catalog of the human gut microbiome and the followingassociation studies in a series of complex diseases highlight the strong connectionbetween intestinal microorganisms and human health. These studies also shows agreat potential of using microbiome-based approaches for early diagnostics, and alsoin therapy and prevention of common diseases such as T2D, CRC, RA, and CHD.

UR - https://soeg.kb.dk/permalink/45KBDK_KGL/fbp0ps/alma99122291925605763

M3 - Ph.D. thesis

BT - Metagenomics Study on the Polymorphism of Gut Microbiota and Their Function on Human Health

PB - Department of Biology, Faculty of Science, University of Copenhagen

ER -