Metagenome-wide Association Studies Research Articles

Influence of the human intestinal microbiome on obesity and metabolic dysfunction.

Recent studies have suggested that there may be a strong link between the gut microbiota, energy extraction and body metabolism. Evidence is accumulating that the intestinal microbiota, in addition to other major factors such as diet and host genetics, contributes to obesity, metabolic dysfunction and diabetes. Both preclinical experimental and human studies have shown that obesity and metabolic dysfunction are characterized by a profound dysbiosis. Several human metagenome-wide association studies have demonstrated highly significant correlations of certain members of intestinal microbiota with obesity and type 2 diabetes. In addition dietary factors that substantially affect microbial composition, microbiota disruption, and the consequence of early-life antibiotic use, may contribute to childhood obesity and metabolic dysfunction. Further evidence for an association between microbiota and metabolic dysfunction has been derived from studies in pregnancy demonstrating that major gut microbial shifts occur during pregnancy thereby affecting host metabolism. In particular, the high rate of obesity following caesarean section could be partially explained by functional alterations in the intestinal microbiota. Obesity and associated metabolic dysfunction emerge from disturbed interactions between the intestinal microbiota, dietary changes and host immune functions. A better understanding of this relationship might lead to better therapies for human metabolic and inflammatory diseases in the future.

Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates

ObjectiveThe assessment of potentially confounding factors affecting colon microbiota composition is essential to the identification of robust microbiome based disease markers. Here, we investigate the link between gut microbiota variation...

The gut microbiome - a new target for understanding, diagnosing and treating disease

The functioning of the human body constitutes a complex interplay of human processes and ‘services’ rendered to us by the 1000 trillion microbial cells we carry. Disruption of this natural microbial flora is linked to infection, autoimmune diseases and cancer, but detailed knowledge about our microbial component remains scarce [1]. Recent technological advances such as metagenomics and next-generation sequencing permit the study of the various microbiota of the human body at a previously unseen scale. These advances have allowed the initiation of the International Human Microbiome Project, aiming at genomically characterizing the totality of human-associated microorganisms (the “microbiome”) [2]. Here, I will present our work on characterizing the human intestinal flora based upon the analysis of high-throughput meta-omics (metagenomics, metatranscriptomics, metaproteomics) data. I will show how the healthy gut flora can be classified “enterotypes” that are independent from host nationality, age, BMI and gender, but linked to nutrition [3]. I will also show how metagenome-wide association studies (MGWAS) can lead to the detection of diagnostic markers for host properties and disease (e.g. in IBD, diabetes and obesity), and aid in further understanding on how the gut flora disturbances contribute to these pathologies. Finally, I will illustrate how gut microbiota-based treatment strategies are emerging, for example through Faecal Microbiota Transplantation (FMT).

Microbiota and diabetes: an evolving relationship

The gut microbiota affects numerous biological functions throughout the body and its characterisation has become a major research area in biomedicine. Recent studies have suggested that gut bacteria play a...