Our research field and previous discoveries
To evaluate and clarify the impact of intestinal bacteria towards their host physiology, we are using Drosophila melanogaster as a model host. The recent award of the 2011 Nobel prize in physiology and medicine partly to Dr Jules Hoffmann for the work of his team on the regulation of Drosophila innate immunity has highlighted the pioneer role of unbiased genetic approaches using this animal model to tackle important biological questions related to host/microbes interactions. Over the last four years Drosophila has also emerged as a powerful animal model to study host-commensal biology. Indeed, in addition to its physiological characteristics with organs remarkably similar to those of mammals and its powerful genetic tools, wild or lab-raised Drosophila carry simple and aero-tolerant bacterial communities easily cultivable in the lab. Drosophila’s microbiota is composed of a maximum of 50 phylotypes with usually 3-5 dominant Lactobacillale and Acetobacteraceae species (including strains of Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus fructivorans, Acetobacter pomorum and Acetobacter tropicalis). The ease to manipulate these commensal bacterial species in the lab coupled to their genetic tractability, underlines the attractivity of this animal model to bypass the complexity encounter in the mammalian setting. This relative simplicity allows focusing on the basic principles and mechanisms governing the mutualistic association of an intestinal microbiota and its host, which are likely to be conserved in the whole animal kingdom including mammals.
In this light, recent reports, including our work, have begun to reveal the impact of the microbiota on the host intestinal epithelium. The Drosophila microbiota promotes immuno-modulation by stimulating the NF-kB-dependent expression of regulators of innate immune signalling and influences epithelial homeostasis by promoting intestinal stem cells activity. Another report suggests that indigenous bacteria influence Drosophila lifespan, supporting the idea that the Drosophila microbiota contributes to its host biology. However, this observation remains controversial. Although it has been shown that Drosophila commensal bacteria influence mating preference and are likely to impact Drosophila ecology in its natural environment, until recently the contribution of the Drosophila microbiota to host physiology was unknown. We have recently demonstrated that the Drosophila microbiota influences host physiology at least in part by promoting host systemic growth upon nutrient scarcity (Fig.1A).
Following this initial observation, we have further identified the bacterial species present in the gut of a laboratory fly strain that develops faster than germ-free siblings. We were able to recapitulate the growth benefit effect of the microbiota by some strains of a single resident bacterial species, Lactobacillus plantarum (Fig.1B). L.plantarum is a commensal species of Drosophila melanogaster, which resides in the intestine and is vertically transmitted to progenies via the deposition of mother’s faeces on the surface of the embryo during egg laying (Fig.1C). This commensal feature most likely stems from the extreme versatility of this bacterial species, which is encountered in a variety of ecological niches, including the human mouth, intestine and vagina. Interestingly this bacterial species has been used for decades as a model lactic acid bacteria and therefore offers vast technical resources and potential. Of note, the ecological flexibility of L.plantarum is reflected by the observation that this species has one of the largest genome known among lactic acid bacteria and is equipped with a large number of genes encoding regulatory, transport and extracellular proteins. Finally, we have shown that our L.plantarum isolates and the isolate WCFS1 of the type strain NCIMB#8826 colonize Drosophila larvae and exert their beneficial effect on larval growth through the host nutrient sensing system, independently of dietary energy extraction. This effect relies on the tissue specific activity of the TOR kinase, which activity is regulated by circulating amino-acids levels and controls the production of systemic hormonal growth signals. These results highlight the marked impact of L.plantarum on host biology and suggest that L.plantarum directly impacts host nutrient assimilation (Fig1.D). More globally these results indicate that the intestinal microbiota should also be envisaged as a factor that influences the systemic growth of its host.
With these recent results, we have now established a powerful gnotobiotic animal model (i.e an animal model with a defined intestinal microbiota) illustrating a beneficial relationship between an animal host and its Lactobacilli commensal.