Abstract
Large-scale ‘meta-omic’ projects are greatly advancing our knowledge of the human microbiome and its specific role in governing health and disease states. A myriad of ongoing studies aim at identifying links between microbial community disequilibria (dysbiosis) and human diseases. However, due to the inherent complexity and heterogeneity of the human microbiome, cross-sectional, case–control and longitudinal studies may not have enough statistical power to allow causation to be deduced from patterns of association between variables in high-resolution omic datasets. Therefore, to move beyond reliance on the empirical method, experiments are critical. For these, robust experimental models are required that allow the systematic manipulation of variables to test the multitude of hypotheses, which arise from high-throughput molecular studies. Particularly promising in this respect are microfluidics-based in vitro co-culture systems, which allow high-throughput first-pass experiments aimed at proving cause-and-effect relationships prior to testing of hypotheses in animal models. This review focuses on widely used in vivo, in vitro, ex vivo and in silico approaches to study host-microbial community interactions. Such systems, either used in isolation or in a combinatory experimental approach, will allow systematic investigations of the impact of microbes on the health and disease of the human host. All the currently available models present pros and cons, which are described and discussed. Moreover, suggestions are made on how to develop future experimental models that not only allow the study of host-microbiota interactions but are also amenable to high-throughput experimentation.
Highlights
A human individual’s microbiota consists of around 100 trillion cells, which represent at least ten times as many cells as human cells constitute the body
Recent large-scale metagenomic sequencing efforts, including those led by the human microbiome project (HMP; National Institutes of Health initiative) [2,3] and the metagenomics of the human intestinal tract (MetaHIT) [4,5] consortia, have convincingly corroborated the notion that humans should be considered as
Conceptualization of experimental models A conceptualized ideal experimental model (Figure 2) for the study of host-microbiota interactions in the gastrointestinal tract (GIT) and one that would allow testing the myriad of hypotheses linking dysbiosis to disease should allow paired wet- and dry-lab experiments and mimic as closely as possible the GIT
Summary
A human individual’s microbiota consists of around 100 trillion cells, which represent at least ten times as many cells as human cells constitute the body. Conceptualization of experimental models A conceptualized ideal experimental model (Figure 2) for the study of host-microbiota interactions in the GIT and one that would allow testing the myriad of hypotheses linking dysbiosis to disease should allow paired wet- and dry-lab experiments and mimic as closely as possible the GIT Such a model should in particular include: i) human GIT cells; ii) human microbiota sustainably growing under anaerobic/microaerophilic conditions; iii) a mucus layer simulating the physical separation of human and microbial cell contingents; and iv) the physico-chemical conditions encountered in the GIT including primarily pH, fluid retention times and dissolved O2 concentrations. Combined experimental approaches in animal and in vitro models could lead to the establishment of causal relationships between microbial community compositions and human diseases
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