Lactobacillus plantarum Promotes Drosophila Systemic Growth by Modulating Hormonal Signals through TOR-Dependent Nutrient Sensing

Institut de Biologie du Développement de Marseille-Luminy, CNRS UMR 6216/Aix-Marseille Universités, 13288 Marseille, France.
Cell metabolism (Impact Factor: 17.57). 09/2011; 14(3):403-14. DOI: 10.1016/j.cmet.2011.07.012
Source: PubMed


There is growing evidence that intestinal bacteria are important beneficial partners of their metazoan hosts. Recent observations suggest a strong link between commensal bacteria, host energy metabolism, and metabolic diseases such as diabetes and obesity. As a consequence, the gut microbiota is now considered a "host" factor that influences energy uptake. However, the impact of intestinal bacteria on other systemic physiological parameters still remains unclear. Here, we demonstrate that Drosophila microbiota promotes larval growth upon nutrient scarcity. We reveal that Lactobacillus plantarum, a commensal bacterium of the Drosophila intestine, is sufficient on its own to recapitulate the natural microbiota growth-promoting effect. L. plantarum exerts its benefit by acting genetically upstream of the TOR-dependent host nutrient sensing system controlling hormonal growth signaling. Our results indicate that the intestinal microbiota should also be envisaged as a factor that influences the systemic growth of its host.

  • Source
    • "Since wild flies develop in and consume decomposed fruit, ethanol is likely a common constituent of their environment. As ethanol is a fuel source for Acetobacter, a prominent fly commensal that modifies insulin and TOR signals in the midgut (Shin et al., 2011;Storelli et al., 2011), it remains possible that the lifespan extension we see from ethanol depends on the microbiota.Since we observed benefits from glucose independent of the microbiota, we were interested in the host response to glucose that extends lifespan. High dietary glucose lowers insulin sensitivity in flies (Musselman et al., 2011), and decreased insulin activity in the gut increases lifespan in the fly (Biteau et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The acquisition of nutrients is essential for maintenance of metabolic processes in all organisms. Nutritional imbalance contributes to myriad metabolic disorders that include malnutrition, diabetes and even cancer. Recently, the importance of macronutrient ratio of food has emerged as a critical factor to determine health outcomes. Here we show that individual modifications to a completely defined diet markedly impact multiple aspects of organism wellbeing in Drosophila melanogaster. Through a longitudinal survey of several diets we demonstrate that increased levels of dietary glucose significantly improve longevity and immunity in adult Drosophila. Our metagenomic studies show that relative macronutrient levels not only influence the host, but also have a profound impact on microbiota composition. However, we found that elevated dietary glucose extended the lifespan of adult flies even when raised in a germ-free environment. Furthermore, when challenged with a chronic enteric infection, flies fed a diet with added glucose had increased survival times even in the absence of an intact microbiota. Thus, in contrast to known links between the microbiota and animal health, our findings uncover a novel microbiota-independent response to diet that impacts host wellbeing. As dietary responses are highly conserved in animals, we believe our results offer a general understanding of the association between glucose metabolism and animal health.
    Full-text · Article · Jan 2016 · Biology Open
  • Source
    • "Using the FlyAtlas tool, we identified that most of these peptidases have a basal expression level enriched in both the adult and larval midguts of the conventional individuals (CONV; i.e, carrying commensal microbes), a signature confirmed in adult midguts by RT-qPCR (Erkosar et al., 2014). Since we hypothesized that Lp WJL may exert its growth-promoting activity during juvenile development by enhancing protein assimilation in the host (Storelli et al., 2011), this observation prompted us to investigate the expression of these peptidase genes by time course RT-qPCR in larval midguts of GF or Lp WJL -associated individuals on a low-nutrition diet (see Figure 1A for detailed experimental scheme). We found the expression profile of 7 peptidases (Jon66Cii, Jon66Ci, Jon44E, Jon65Ai, Jon99Ci, CG18179, and CG18180) presents a robust and detectable transcriptional signature during larval development (Figures 1B–1I). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The microbial environment impacts many aspects of metazoan physiology through largely undefined molecular mechanisms. The commensal strain Lactobacillus plantarumWJL (LpWJL) sustains Drosophila hormonal signals that coordinate systemic growth and maturation of the fly. Here we examine the underlying mechanisms driving these processes and show that LpWJL promotes intestinal peptidase expression, leading to increased intestinal proteolytic activity, enhanced dietary protein digestion, and increased host amino acid levels. LpWJL-mediated peptidase upregulation is partly driven by the peptidoglycan recognition and signaling cascade PGRP-LE/Imd/Relish. Additionally, this mutualist-mediated physiological benefit is antagonized upon pathogen infection. Pathogen virulence selectively impedes LpWJL-mediated intestinal peptidase activity enhancement and juvenile growth promotion but does not alter growth of germ-free animals. Our study reveals the adaptability of host physiology to the microbial environment, whereby upon acute infection the host switches to pathogen-mediated host immune defense at the expense of mutualist-mediated growth promotion.
    Full-text · Article · Oct 2015 · Cell Host & Microbe
  • Source
    • "Similarly, Storelli et al. (2011) showed that infection by Lactobacillus plantarum correlates with upregulated IIS pathway when comparing to GF flies. L. plantarum exhibits growth-promoting effect in L. plantarum-monoassosiated D. melanogaster (Storelli et al. 2011). This indicates that L. plantarum may be required for normal body size in D. melanogaster. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Microbiota is known to interact with metabolic and regulatory networks of the host affecting its fitness. The composition of microbiota was shown to change throughout the host aging. Such changes can be likely caused by aging process or, vice versa, changes in microbiota composition can impact the aging process. It is suggested that microbiota plays an important role in life span determination. Several species from the genus Drosophila, especially D. melanogaster, are powerful models to study many biological processes including microbiota functioning and its effects on the host aging. The host fitness can be substantially affected by endosymbiotic bacteria such as Wolbachia that infects up to two-thirds of insects taxa, including Drosophila. Wolbachia was shown to significantly affect Drosophila aging and life span. However, the molecular mechanisms underlying interactions between Wolbachia and Drosophila remain mostly unknown. In this chapter, we summarize data suggesting that Wolbachia-Drosophila molecular cross-talk associated with life span determination and aging can occur through the immune deficiency pathway, stress-induced JNK pathway, insulin/IGF signaling pathway, ecdysteroid biosynthesis and signaling pathway, as well as through the heat shock and autophagy-specific genes/proteins.
    Full-text · Chapter · Jun 2015
Show more