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• W2167163043 abstract "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. 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. Drosophila microbiota promotes optimal larval development upon nutrient scarcity Lactobacillus plantarum recapitulates the microbiota growth-promoting effect L. plantarum association correlates with hormonal growth signaling modulation L. plantarum growth-promoting effect requires TOR-dependent host nutrient sensing For historical reasons and biomedical concerns, bacteria have been mainly studied for their harmful effects on human health. However, growing evidence suggests that bacteria are also important beneficial partners of metazoans (Fraune and Bosch, 2010Fraune S. Bosch T.C. Why bacteria matter in animal development and evolution.Bioessays. 2010; 32: 571-580Crossref PubMed Scopus (165) Google Scholar). Interactions between bacteria and their animal hosts can be viewed in terms of a continuum ranging from symbiosis or commensalism to pathogenicity (Hooper and Gordon, 2001Hooper L.V. Gordon J.I. Commensal host-bacterial relationships in the gut.Science. 2001; 292: 1115-1118Crossref PubMed Scopus (1652) Google Scholar). The term commensalism comes from the Medieval Latin “commensalis,” meaning “eating at the same table,” and refers to a host-microbial interaction that does not result in perceptible host damage (Casadevall and Pirofski, 2000Casadevall A. Pirofski L.A. Host-pathogen interactions: basic concepts of microbial commensalism, colonization, infection, and disease.Infect. Immun. 2000; 68: 6511-6518Crossref PubMed Scopus (315) Google Scholar). As opposed to saprophytes that live independently of an animal host, commensal bacteria colonize their host generally at birth, through vertical transfer, and are acquired constantly during the host life from the environment through ingestion. Therefore, numerous commensal bacteria reside in the host intestine, a nutrient-rich environment, where they form a vast, complex, and dynamic consortium of indigenous microbial species collectively referred as the microbiota (Hooper and Gordon, 2001Hooper L.V. Gordon J.I. Commensal host-bacterial relationships in the gut.Science. 2001; 292: 1115-1118Crossref PubMed Scopus (1652) Google Scholar). Although it has been known for decades that humans carry ten times more bacterial cells than their own cells (Savage, 1977Savage D.C. Microbial ecology of the gastrointestinal tract.Annu. Rev. Microbiol. 1977; 31: 107-133Crossref PubMed Scopus (1560) Google Scholar), the human microbiota characterization has previously been hampered by the difficulty of cultivating most gut bacterial species in laboratory conditions. Thanks to the revolution of deep-sequencing technologies, the commensal metagenome now starts to be unraveled (Furrie, 2006Furrie E. A molecular revolution in the study of intestinal microflora.Gut. 2006; 55: 141-143Crossref PubMed Scopus (55) Google Scholar). Recent studies suggest that it contains about 150 times more genes than the human gene complement and shows a significant enrichment in genes encoding metabolic activities (Gill et al., 2006Gill S.R. Pop M. Deboy R.T. Eckburg P.B. Turnbaugh P.J. Samuel B.S. Gordon J.I. Relman D.A. Fraser-Liggett C.M. Nelson K.E. Metagenomic analysis of the human distal gut microbiome.Science. 2006; 312: 1355-1359Crossref PubMed Scopus (2888) Google Scholar, Nelson et al., 2010Nelson K.E. Weinstock G.M. Highlander S.K. Worley K.C. Creasy H.H. Wortman J.R. Rusch D.B. Mitreva M. Sodergren E. Chinwalla A.T. et al.Human Microbiome Jumpstart Reference Strains ConsortiumA catalog of reference genomes from the human microbiome.Science. 2010; 328: 994-999Crossref PubMed Scopus (466) Google Scholar, Qin et al., 2010Qin J. Li R. Raes J. Arumugam M. Burgdorf K.S. Manichanh C. Nielsen T. Pons N. Levenez F. Yamada T. et al.MetaHIT ConsortiumA human gut microbial gene catalogue established by metagenomic sequencing.Nature. 2010; 464: 59-65Crossref PubMed Scopus (6159) Google Scholar). Hence, the idea that the intestinal microbiota constitutes an additional organ has recently re-emerged (Bocci, 1992Bocci V. The neglected organ: bacterial flora has a crucial immunostimulatory role.Perspect. Biol. Med. 1992; 35: 251-260Crossref PubMed Scopus (102) Google Scholar, O'Hara and Shanahan, 2006O'Hara A.M. Shanahan F. The gut flora as a forgotten organ.EMBO Rep. 2006; 7: 688-693Crossref PubMed Scopus (1604) Google Scholar). Intestinal bacteria communities shape the nutrient environment of the host by contributing enzymatic activities that break down otherwise nondigestible carbohydrates (Hooper et al., 2002Hooper L.V. Midtvedt T. Gordon J.I. How host-microbial interactions shape the nutrient environment of the mammalian intestine.Annu. Rev. Nutr. 2002; 22: 283-307Crossref PubMed Scopus (1063) Google Scholar). They also salvage energy through carbohydrate fermentation, leading to the production of short-chain fatty acids (Venema, 2010Venema K. Role of gut microbiota in the control of energy and carbohydrate metabolism.Curr. Opin. Clin. Nutr. Metab. Care. 2010; 13: 432-438Crossref PubMed Scopus (63) Google Scholar). In this light, the gut microbiota is now deemed a “host” factor that influences energy uptake (Bäckhed et al., 2005Bäckhed F. Ley R.E. Sonnenburg J.L. Peterson D.A. Gordon J.I. Host-bacterial mutualism in the human intestine.Science. 2005; 307: 1915-1920Crossref PubMed Scopus (3191) Google Scholar). The link between commensal bacterial communities and energy metabolism is further supported by recent evidence suggesting a strong association between the composition of the intestinal microbiota and metabolic diseases such as diabetes and obesity (Burcelin et al., 2009Burcelin R. Luche E. Serino M. Amar J. The gut microbiota ecology: a new opportunity for the treatment of metabolic diseases?.Front. Biosci. 2009; 14: 5107-5117Crossref Scopus (43) Google Scholar, Cani and Delzenne, 2009Cani P.D. Delzenne N.M. The role of the gut microbiota in energy metabolism and metabolic disease.Curr. Pharm. Des. 2009; 15: 1546-1558Crossref PubMed Scopus (627) Google Scholar). However, the molecular mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined (Sekirov et al., 2010Sekirov I. Russell S.L. Antunes L.C. Finlay B.B. Gut microbiota in health and disease.Physiol. Rev. 2010; 90: 859-904Crossref PubMed Scopus (2160) Google Scholar). Important unsolved basic questions are still standing in the field. For instance, do specific bacterial strains account for the benefit or the damage caused by the microbiota, and if so, which ones? In addition, besides optimizing energy harvest, do commensal bacterial species influence other systemic physiological parameters? Bacterial complement referred as “probiotics” have now been used for decades in the farming industry to promote growth of poultry, calves, and pigs; however, the precise mechanisms underlying these enhancements are still highly debated (Delzenne and Reid, 2009Delzenne N. Reid G. No causal link between obesity and probiotics.Nat. Rev. Microbiol. 2009; 7 (author reply 901): 901Crossref PubMed Scopus (44) Google Scholar, Ehrlich, 2009Ehrlich S.D. Probiotics - little evidence for a link to obesity.Nat. Rev. Microbiol. 2009; 7 (author reply 901): 901Crossref PubMed Scopus (31) Google Scholar, Raoult, 2009Raoult D. Probiotics and obesity: a link?.Nat. Rev. Microbiol. 2009; 7: 616Crossref PubMed Scopus (66) Google Scholar, Simon, 2005Simon O. Micro-organisms as feed additives - probiotics.Advances in Pork Production. 2005; : 161-167Google Scholar). These debates highlight the need of using experimental models to evaluate the role of intestinal bacteria as animal growth promoters. To tackle these biological questions, we used Drosophila melanogaster as a host model. Indeed, over the last 4 years Drosophila has emerged as a powerful animal model to study host-commensal biology. Wild or lab-raised Drosophila carry simple bacterial communities composed of a maximum of 20 species with usually 3–4 dominant Lactobacillale and Acetobacteraceae species (Corby-Harris et al., 2007Corby-Harris V. Pontaroli A.C. Shimkets L.J. Bennetzen J.L. Habel K.E. Promislow D.E. Geographical distribution and diversity of bacteria associated with natural populations of Drosophila melanogaster.Appl. Environ. Microbiol. 2007; 73: 3470-3479Crossref PubMed Scopus (153) Google Scholar, Cox and Gilmore, 2007Cox C.R. Gilmore M.S. Native microbial colonization of Drosophila melanogaster and its use as a model of Enterococcus faecalis pathogenesis.Infect. Immun. 2007; 75: 1565-1576Crossref PubMed Scopus (210) Google Scholar, Ren et al., 2007Ren C. Webster P. Finkel S.E. Tower J. Increased internal and external bacterial load during Drosophila aging without life-span trade-off.Cell Metab. 2007; 6: 144-152Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar, Ryu et al., 2008Ryu J.H. Kim S.H. Lee H.Y. Bai J.Y. Nam Y.D. Bae J.W. Lee D.G. Shin S.C. Ha E.M. Lee W.J. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila.Science. 2008; 319: 777-782Crossref PubMed Scopus (538) Google Scholar). Recent reports, including our work, have begun to illustrate the molecular dialog between the microbiota and the intestinal epithelium. The Drosophila microbiota promotes immunomodulation by triggering the expression of negative regulators of innate immune signaling in intestinal epithelial cells (Lhocine et al., 2008Lhocine N. Ribeiro P.S. Buchon N. Wepf A. Wilson R. Tenev T. Lemaitre B. Gstaiger M. Meier P. Leulier F. PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling.Cell Host Microbe. 2008; 4: 147-158Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, Ryu et al., 2008Ryu J.H. Kim S.H. Lee H.Y. Bai J.Y. Nam Y.D. Bae J.W. Lee D.G. Shin S.C. Ha E.M. Lee W.J. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila.Science. 2008; 319: 777-782Crossref PubMed Scopus (538) Google Scholar) and influences epithelial homeostasis through the promotion of intestinal stem cell activity (Buchon et al., 2009Buchon N. Broderick N.A. Chakrabarti S. Lemaitre B. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila.Genes Dev. 2009; 23: 2333-2344Crossref PubMed Scopus (462) Google Scholar). A previous report suggested that the indigenous bacteria promote Drosophila lifespan (Brummel et al., 2004Brummel T. Ching A. Seroude L. Simon A.F. Benzer S. Drosophila lifespan enhancement by exogenous bacteria.Proc. Natl. Acad. Sci. USA. 2004; 101: 12974-12979Crossref PubMed Scopus (203) Google Scholar), supporting the idea that the Drosophila microbiota contributes somehow to its host biology; however, this observation is now seriously questioned (Ren et al., 2007Ren C. Webster P. Finkel S.E. Tower J. Increased internal and external bacterial load during Drosophila aging without life-span trade-off.Cell Metab. 2007; 6: 144-152Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar). Although it has recently been shown that Drosophila commensal bacteria influence their host mating preference and are likely to severely impact Drosophila ecology in its natural environment (Sharon et al., 2010Sharon G. Segal D. Ringo J.M. Hefetz A. Zilber-Rosenberg I. Rosenberg E. Commensal bacteria play a role in mating preference of Drosophila melanogaster.Proc. Natl. Acad. Sci. USA. 2010; 107: 20051-20056Crossref PubMed Scopus (499) Google Scholar), the contribution of the microbiota to its host physiology is currently unknown. In this study, we demonstrate that the Drosophila gut microbiota promotes larval growth upon nutrient scarcity. We further identify the bacterial species present in the gut of our laboratory fly strain and show that one of them, Lactobacillus plantarum, recapitulates the microbiota growth-promoting effect. Finally, we show that L. plantarum exerts its beneficial effect on larval growth through the host nutrient sensing system, which relies on tissue-specific TOR activity controlling systemic hormonal growth signaling. The growth phase of insects is restricted to the larval stages, where size gain can be spectacular in certain species. In Drosophila melanogaster, individuals increase their size by about 200-fold during the three larval instars (Robertson, 1963Robertson F.W. The ecological genetics of growth in Drosophila 6. The genetic correlation between the duration of the larval period and body size in relation to larval diet.Genet. Res. 1963; 4: 74-92Crossref Scopus (113) Google Scholar). This massive larval growth is fully dependent on food richness, since culture on poor-nutrient medium severely impacts Drosophila systemic growth and results in a marked delay of adult emergence (Layalle et al., 2008Layalle S. Arquier N. Léopold P. The TOR pathway couples nutrition and developmental timing in Drosophila.Dev. Cell. 2008; 15: 568-577Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar, Robertson, 1963Robertson F.W. The ecological genetics of growth in Drosophila 6. The genetic correlation between the duration of the larval period and body size in relation to larval diet.Genet. Res. 1963; 4: 74-92Crossref Scopus (113) Google Scholar). In order to test the putative contribution of Drosophila microbiota to its host systemic growth, we compared the timing of adult emergence of germ-free (GF) and conventionally reared (CR) siblings. Although no significant difference was observed between GF and CR larvae raised on rich medium (Figures 1A and 1B ), spectacular growth delays were noticed when larvae were reared on poor-nutrient conditions. Consistent with previous reports, reduction of the amount of yeast extract in the medium results in about 2.5 days delay of adult emergence for CR individuals (Figures 1A and 1B) (Layalle et al., 2008Layalle S. Arquier N. Léopold P. The TOR pathway couples nutrition and developmental timing in Drosophila.Dev. Cell. 2008; 15: 568-577Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar). Strikingly, this delay was more than doubled for individuals raised in GF conditions, since GF adults emerged 2.9 days later than their CR siblings (Figures 1A and 1B; Table S1). These data demonstrate that although the Drosophila microbiota is dispensable for larval growth, it is necessary for optimal larval development upon nutrient scarcity. In order to identify which commensal bacterial species mediate this effect, we characterized the bacterial communities associated with our CR fly strain. To this end, we generated bacterial 16S rRNA gene libraries from whole flies and dissected midguts. Analyses of clone sequences indicate that each library contains 16S clones of three bacterial phylotypes, one unique to each library (an Aerococcus spp. strain identified in whole flies and a Corynebacterium variabile strain identified in midguts) and two common dominant species (Enterococcus faecalis and Lactobacillus plantarum) (Table 1). These latter species were previously found to be associated with adult Drosophila intestines and are likely to be commensal with Drosophila (Cox and Gilmore, 2007Cox C.R. Gilmore M.S. Native microbial colonization of Drosophila melanogaster and its use as a model of Enterococcus faecalis pathogenesis.Infect. Immun. 2007; 75: 1565-1576Crossref PubMed Scopus (210) Google Scholar, Ryu et al., 2008Ryu J.H. Kim S.H. Lee H.Y. Bai J.Y. Nam Y.D. Bae J.W. Lee D.G. Shin S.C. Ha E.M. Lee W.J. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila.Science. 2008; 319: 777-782Crossref PubMed Scopus (538) Google Scholar). We then tested whether L. plantarum and E. faecalis have the ability to colonize Drosophila gut. To this end, GF embryos were cultured on rich or poor medium supplemented with 108 cfu of either bacterial species, and internal bacterial loads were quantified at different developmental stages following this inoculation (Figures 2A and S1A). One day after the inoculation, both L. plantarum and E. faecalis were detected in larvae, suggesting that both species can colonize young larvae. However, kinetics between L. plantarum and E. faecalis began to diverge the following day. L. plantarum load kept on increasing during larval development, whereas E. faecalis titers constantly dropped down, ultimately reaching an undetectable level at late larval stage (Figures 2A and S1A). These data suggest that L. plantarum, unlike E. faecalis, has the ability to remain associated with Drosophila long after an initial colonization. The fact that similar L. plantarum quantities were found in whole individuals and in dissected midguts demonstrates that L. plantarum resides in the midgut after colonization (Figures 2B, 2C, and S1B). Finally, we tested whether the presence of L. plantarum in the gut required constant reassociation by feeding on contaminated medium. To this end, young larvae colonized by L. plantarum were surface sterilized and transferred to GF culture medium. The bacterial loads of larvae as well as the bacterial load on the medium were quantified over time. In this experimental setting, L. plantarum titers were similar to those observed in nontransferred larvae. In addition, L. plantarum was able to efficiently recolonize the medium (Figures 2D, 2E, S1C, and S1D). These results demonstrate that L. plantarum remains associated with its host upon transfer and that larval gut-derived L. plantarum has the ability to recolonize the entire larval niche upon transfer. Although these results highlight the commensal behavior of L. plantarum and Drosophila larvae, we cannot exclude that L. plantarum is constantly recolonizing its host by repeated ingestion. Taken collectively, these results reveal the potent ability of L. plantarum to efficiently colonize the whole larval niche, including its host midgut and the external media, and to resist the passage through the digestive tract of its host.Table 1Bacterial Species Associated with Our Conventionally Reared Wild-Type Fly StrainCRyw Whole Body LibraryPhylotypeClosest strain% identityEnterococcus faecalisEnterococcus faecalis V58399%Lactobacillus plantarumLactobacillus plantarum WCFS199%Aerococcus spp.Aerococcus viridans ATCC1156397%CRyw Adult Midgut LibraryPhylotypeClosest strain% identityEnterococcus faecalisEnterococcus faecalis V58399%Lactobacillus plantarumLactobacillus plantarum WCFS199%Corynebacterium variabileCorynebacterium variabile DSM2013298% Open table in a new tab We next asked whether the parameters of the Drosophila monoassociation with L. plantarum (kinetics of persistence and internal loads) mirror those of indigenous bacteria in CR individuals. Indeed, L. plantarum loads fluctuated in between different developmental stages but in a very stereotyped and reproducible manner. L. plantarum loads constantly increase during the larval stages, reaching a maximum at midpupal stage (Figure 2A). This was followed by a dramatic fall during late metamorphosis and by a reassociation upon adult emergence, illustrated by an increasing amount of bacteria during the adult life (Figure 2A). Similar kinetics of the whole bacterial population persistence and loads were observed during the larval, pupal, and early adult stages of CR individuals (Figure 2G). In contrast, internal bacterial loads following adult emergence were slightly different between L. plantarum-associated and CR adults (Figures 2A and 2H). Since vertical transfer is a hallmark of the natural process of microbiota acquisition, we tested whether L. plantarum could be efficiently transmitted from the parents to their progenies. As shown in Figure 2F, L. plantarum loads and kinetics of persistence in progenies of L. plantarum-associated parents followed the same pattern as the one observed in artificially L. plantarum-associated flies or as the whole bacterial population in CR flies (Figures 2A, 2F, and 2G). Taken together, these experiments demonstrate that the protocol used to associate GF individuals with L. plantarum faithfully recapitulates a natural pattern of bacterial colonization of CR individuals, at least during larval, pupal, and early adult stages. Having demonstrated that L. plantarum colonizes the larval niche as a natural microbiota, we tested whether L. plantarum on its own sustains the development of larvae raised on poor-nutrient media. L. plantarum association in poor-condition medium was sufficient to accelerate larval growth and resulted in earlier emergence of adults (Figures 3A and 3B ; Table S1). This effect was not observed in rich-medium condition (Figures 3A and 3B). This growth-promoting effect, which was observed in different poor-medium conditions, results in a reduction of all three larval instars (Figures 3C and 3D). Strikingly, the presence of L. plantarum was sufficient to allow development of larvae in the complete absence of yeast extract, a condition that normally led to lethality of GF late first instar larvae (Figure 3C). Importantly, this beneficial effect was neither observed upon colonization of GF larvae with another bacterial species, E. faecalis, which does not persist in its host, nor with another strain of L. plantarum isolated in our lab and fully capable of colonizing the larvae and the medium (Figures 3A, 3B, and 3E–3H). Importantly, several other strains of L. plantarum isolated independently from flies cultivated in our or other labs are beneficial, as well as the reference L. plantarum strain, whose genome is sequenced (data not shown; Figures S2 and S4). This suggests that many L. plantarum strains exert a specific effect on systemic larval growth that is not a mere trophic effect of adding organic matter to the fly medium, but rather relies on a specific biological activity of these strains. Finally, we show that the beneficial effect of L. plantarum on the developmental timing is also vertically transmitted from L. plantarum-associated parents to their progenies (Figure 3I). Altogether, these observations demonstrate that association with several strains of L. plantarum accelerates larval development upon nutrient scarcity and results in an earlier emergence of adults compared to GF animals. These data reveal that some strains of a single Drosophila commensal bacterial species, L. plantarum, are sufficient to recapitulate the beneficial effect of a naturally acquired microbiota. To further characterize how L. plantarum impacts larval growth, we analyzed the final adult size, a parameter that is directly dependent on the larval growth phase. To this end, we compared the weight of young adults appearing from larvae raised on GF or L. plantarum-contaminated media. As for the length of the larval stages, we did not observe any significant differences in the weight of adults developing from GF and L. plantarum-associated larvae grown on rich diet (Figure 4A ). Similarly, when larvae were grown on poor medium, no significant difference was observed between GF and L. plantarum-associated individuals (Figure 4B). However, adults developing from either GF or L. plantarum-associated larvae grown on poor diet were lighter than individuals grown in rich conditions (Figures 4A and 4B). Given that L. plantarum reduces the length of the growth phase without affecting the final size of the individual, we hypothesized that L. plantarum increases the larval growth rate. To test this, we compared the size of L. plantarum-associated versus GF larvae from L1 larvae to pupae. Data presented in Figures 4C and 4D clearly show a 2-fold increase in the growth rate of L. plantarum-associated larvae raised on a poor diet, whereas no impact on the growth rate is observed when larvae are raised on a rich diet. These results demonstrate that L. plantarum association enhances systemic growth upon nutrient scarcity by promoting larval growth rate and reducing the duration of the growth period. In Drosophila, the duration of the larval period and the larval growth rate are controlled by two circulating hormones: the steroid hormone Ecdysone (Ecd) and the Drosophila insulin-like peptides (dILPs), respectively (Hietakangas and Cohen, 2009Hietakangas V. Cohen S.M. Regulation of tissue growth through nutrient sensing.Annu. Rev. Genet. 2009; 43: 389-410Crossref PubMed Scopus (207) Google Scholar). To test if the presence of L. plantarum directly impacts these growth signals, we compared the levels of molecular readouts of these signals in GF and L. plantarum-associated larvae. The expression of the transcription factor E74B, one of the “early” genes that responds to increasing Ecd titers, is classically used as a molecular marker of Ecd activity (Karim and Thummel, 1991Karim F.D. Thummel C.S. Ecdysone coordinates the timing and amounts of E74A and E74B transcription in Drosophila.Genes Dev. 1991; 5: 1067-1079Crossref PubMed Scopus (107) Google Scholar). Figure 5A shows that L. plantarum association did not increase the E74B mRNA levels until day 7 AED; however, from then E74B mRNA levels sharply peaked in L. plantarum-associated larvae, while the peak was less acute and delayed in GF larvae. Of note, in GF larvae E74B mRNA levels were already increased (albeit with low statistical significance) at day 9 AED, but no larvae pupariated at this time point (pupariation started at day 11 AED, Figure 3D). These results indicate that L. plantarum association correlates with an earlier and stronger Ecd peak in third instar larvae. We then used the InR gene expression as a readout for systemic dILP activity. Indeed, the InR gene transcription is under the direct negative regulation of the InR signaling pathway via the activity of the FoxO transcription factor. InR expression is therefore used as a negative molecular marker of systemic dILP activity: low InR expression correlating with high dILP activity (Puig and Tjian, 2005Puig O. Tjian R. Transcriptional feedback control of insulin receptor by dFOXO/FOXO1.Genes Dev. 2005; 19: 2435-2446Crossref PubMed Scopus (257) Google Scholar). As shown in Figure 5B, InR expression was always lower in L. plantarum-associated larvae than in GF larvae. These results show that L. plantarum association correlates with increased systemic InR signaling during larval growth. Taken together, our observations support the notion that L. plantarum association, albeit with distinct kinetics, enhances the systemic production of two hormonal growth signals. In Drosophila, TOR pathway modulates hormonal signals regulating larval growth in a tissue-specific manner (Hietakangas and Cohen, 2009Hietakangas V. Cohen S.M. Regulation of tissue growth through nutrient sensing.Annu. Rev. Genet. 2009; 43: 389-410Crossref PubMed Scopus (207) Google Scholar). While TOR directly controls Ecd production by the prothoracic gland during the mid-third larval instar (Layalle et al., 2008Layalle S. Arquier N. Léopold P. The TOR pathway couples nutrition and developmental timing in Drosophila.Dev. Cell. 2008; 15: 568-577Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar), the regulation of InR signaling is more complex and implicates cross-talks between different tissues. It has been shown that systemic InR signaling is regulated by a remote control of dILP secretion by neurons through TOR activity in the fat body (Colombani et al., 2003Colombani J. Raisin S. Pantalacci S. Radimerski T. Montagne J. Léopold P. A nutrient sensor mechanism controls Drosophila growth.Cell. 2003; 114: 739-749Abstract Full Text Full Text PDF PubMed Scopus (564) Google Scholar, Géminard et al., 2009Géminard C. Rulifson E.J. Léopold P. Remote control of insulin secretion by fat cells in Drosophila.Cell Metab. 2009; 10: 199-207Abstract Full Text Full Text PDF PubMed Scopus (367) Google Scholar). Since our results suggest that L. plantarum association impacts b" @default.
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• W2167163043 title "Lactobacillus plantarum Promotes Drosophila Systemic Growth by Modulating Hormonal Signals through TOR-Dependent Nutrient Sensing" @default.
• W2167163043 cites W1245819034 @default.
• W2167163043 cites W1514300652 @default.
• W2167163043 cites W1924638511 @default.
• W2167163043 cites W1972686367 @default.
• W2167163043 cites W1980077364 @default.
• W2167163043 cites W1980914602 @default.
• W2167163043 cites W1996648257 @default.
• W2167163043 cites W2003788503 @default.
• W2167163043 cites W2011055466 @default.
• W2167163043 cites W2019703934 @default.
• W2167163043 cites W2023046869 @default.
• W2167163043 cites W2032295744 @default.
• W2167163043 cites W2032685334 @default.
• W2167163043 cites W2038984982 @default.
• W2167163043 cites W2044178718 @default.
• W2167163043 cites W2051178873 @default.
• W2167163043 cites W2052683965 @default.
• W2167163043 cites W2057590849 @default.
• W2167163043 cites W2064865357 @default.
• W2167163043 cites W2069581607 @default.
• W2167163043 cites W2080700065 @default.
• W2167163043 cites W2091220273 @default.
• W2167163043 cites W2092586583 @default.
• W2167163043 cites W2098421609 @default.
• W2167163043 cites W2099030642 @default.
• W2167163043 cites W2100701743 @default.
• W2167163043 cites W2102672175 @default.
• W2167163043 cites W2105575647 @default.
• W2167163043 cites W2106389553 @default.
• W2167163043 cites W2110235509 @default.
• W2167163043 cites W2112024369 @default.
• W2167163043 cites W2117727476 @default.
• W2167163043 cites W2120459847 @default.
• W2167163043 cites W2125826054 @default.
• W2167163043 cites W2137019479 @default.
• W2167163043 cites W2145336165 @default.
• W2167163043 cites W2149351690 @default.
• W2167163043 cites W2153235420 @default.
• W2167163043 cites W2153497031 @default.
• W2167163043 cites W2154789865 @default.
• W2167163043 cites W2165192354 @default.
• W2167163043 cites W2168135989 @default.
• W2167163043 cites W2170025869 @default.
• W2167163043 cites W2327646444 @default.
• W2167163043 doi "https://doi.org/10.1016/j.cmet.2011.07.012" @default.
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