Rapid development of metagenomics sequencing technology and big cohort studies allow us to integrate gut microbiome profiles with host clinical phenotypes, to identify candidate disease-related microbial features in a large scale. All the evidence pinpoints to the critical roles of gut microbiota in developing complex diseases. Human infants born from mothers with immune-related diseases presented altered gut microbial compositions which was further proved to have the potential to trigger adaptive immune response.
In mice studies, gut microbiota has been shown to be essential for germ-free animal models to develop inflammatory bowel disease (IBD). The gut microbiome has been involved in digesting food, training host immunity, regulating gut endocrine function and neurological signaling, modifying drug action and metabolism, eliminating toxins, and producing numerous compounds that influence the host.
The human intestines are colonized by a vast number of bacteria, archaea, microbial eukaryotes, and viruses, as abundant as our somatic cells, which are collectively known as the gut microbiome. Recently, the contribution of the gut microbiome to the development of complex human diseases has increasingly been recognized - and become a booming field of research. For instance, GWAS can only explain the heritability of type 2 diabetes (T2D) and Crohn's disease with 6% and 20% success, respectively. However, genetics can only explain a limited proportion of an individual's risk of developing a complex disease. Genome-wide association studies (GWAS) have dissected the genetic architecture of human complex diseases, which has advanced our understanding of disease etiology and promoted the development of genome-based therapy. Highlightsĭecoding microbial genomes to understand their functional roles in human complex diseases Finally, state-of-the-art techniques have been highlighted which may contribute to a mechanistic understanding of the gut microbiome in human complex diseases and promote the development of the gut microbiome-based personalized medicine. We further introduce artificial tools in decoding microbial genomes to profile their functionalities. In this review, we summarize the roles of the gut microbiome in complex diseases from its functional perspective. Therefore, decoding the microbial genomes has been an important strategy to shed light on their functional potential. Besides this, increasing pieces of evidence now highlight that the intestinal microbiota may contribute substantially to the health and disease of the human host via their metabolic molecules. The etiology of complex diseases is not yet clear, but they are traditionally thought to be caused by genetics and environmental factors (e.g., dietary habits), and by their interactions. Complex diseases such as cardiovascular disease (CVD), obesity, inflammatory bowel disease (IBD), kidney disease, type 2 diabetes (T2D), and cancer have become a major burden to public health and affect more than 20% of the population worldwide.
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