The Mammalian Gut Microbiome, Immune Responses and Disease: From Observational to Causal Relationships

The mammalian gut is the largest organ of adaptive immune responses with a total surface area of 300 m2 of the gut epithelium. The intestinal mucosa contains at least 80% of the body’s activated B cells [1]. The adaptive immune responses mainly consist of secretory immunoglobulin A (IgA) antibodies produced by B cells which have converted to plasma cells in the gut submucosa [2,3]. The bacteria present in the gut are mainly Proteobacteria, Bacteriodetes, Firmicutis, and Actinobacteria (>90%) [4], mostly located in the colon. The total number of gut bacteria has been estimated to be 1014 [4]. They are either commensal or symbiotic, sometimes pathogenic. Besides bacteria, various viruses, fungi, protozoa and helminths can populate the gut, often as pathogens. A disturbance of the gut microbiota accompanied by illness is defined as dysbiosis [5]. The residual and potentially pathogenic gut microbiomes have attracted much attention recently, since their composition was shown to be temporarily correlated with changes in mucosal and systemic immune responses [6]. Animal models have played a major role in elucidating microbiome-host relationships and in improving a mechanistic understanding of gut microbehost relationship [5]. However, there are still gaps in the knowledge of the molecular mechanisms underlying the interactions of the gut microbiome with host functions such as immune responsiveness, and with enteric and extra-intestinal disease development [6]. Here, new data on the bacterial microbiome will be reviewed, which were obtained with the aim to identify and analyse such causal relationships. Abstract