Dissecting cause and effect in host-microbiome interactions using the combined worm-bug model system

Marina Ezcurra

doi:10.1007/s10522-018-9752-x

Marina Ezcurra

Open Access

https://doi.org/10.1007/s10522-018-9752-x

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Abstract

High-throughput molecular studies 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 we need robust experimental models that allow the systematic manipulation of variables to test the multitude of hypotheses arisen from large-scale ‘meta-omic’ projects. The nematode C. elegans combined with bacterial models offers an avenue to dissect cause and effect in host-microbiome interactions. This combined model allows the genetic manipulation of both host and microbial genetics and the use of a variety of tools, to identify pathways affecting host health. A number of recent high impact studies have used C. elegans to identify microbial pathways affecting ageing and longevity, demonstrating the power of the combined C. elegans-bacterial model. Here I will review the current state of the field, what we have learned from using C. elegans to study gut microbiome and host interactions, and the potential of using this model system in the future.

Highlights

Humans coexist in a mutualistic relationship with a diverse gut microbial ecosystem consisting of mainly bacteria, and viruses, fungi and protozoa
Combined data from the MetaHit and the Human Microbiome Project have provided the most comprehensive view of the composition of the human gut microbiota, identifying a total of 2172 species isolated from human beings, classified into 12 different phyla, of which the large majority belong to the phyla Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes (Schloissnig et al 2012; Arumugam et al 2011; Gill et al 2006; Metheet al. 2012)
B. subtilis is known to extend lifespan compared to E. coli (Garsin 2003), and Gusarov et al showed that the mechanisms of these longevity effects involve bacterial production of nitric oxide (NO) in the worm gut, which diffuses to other tissues and initiates a signalling cascade, resulting in a transcriptional response

Summary

Introduction

Humans coexist in a mutualistic relationship with a diverse gut microbial ecosystem consisting of mainly bacteria, and viruses, fungi and protozoa. In flies recent studies have identified microbial pathways affecting ageing and longevity in C. elegans (Table 1), opening for the possibility to further develop this model to understand the role of the gut microbiota in disease states and ageing.

Results

Conclusion