A bacteria-regulated gut peptide determines host dependence on specific bacteria to support host juvenile development and survival.

BACKGROUND: Commensal microorganisms have a significant impact on the physiology of host animals, including Drosophila. Lactobacillus and Acetobacter, the two most common commensal bacteria in Drosophila, stimulate fly development and growth, but the mechanisms underlying their functional interactions remain elusive. RESULTS: We found that imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor binding protein 7, is expressed in gut enterocytes in a bacteria-dependent manner, determining host dependence on specific bacteria for host development. Imp-L2 mutation abolished the stimulatory effects of Lactobacillus, but not of Acetobacter, on fly larval development. The lethality of the Imp-L2 mutant markedly increased under axenic conditions, which was reversed by Acetobacter, but not Lactobacillus, re-association. The host dependence on specific bacteria was determined by Imp-L2 expressed in enterocytes, which was repressed by Acetobacter, but not Lactobacillus. Mechanistically, Lactobacillus and Acetobacter differentially affected steroid hormone-mediated Imp-L2 expression and Imp-L2-specific FOXO regulation. CONCLUSIONS: Our finding may provide a way how host switches dependence between different bacterial species when benefiting from varying microbiota.

Taxon-Specific Effects of Lactobacillus on Drosophila Host Development.

Commensal microbiota heavily influence metazoan host physiology. Drosophila melanogaster has been proven a valuable animal model for studying many aspects of host-microbiota interaction. Lactobacillus are the most common human probiotics and are also one of the major symbiotic bacteria in Drosophila. Although the beneficial effects of Lactobacillus on fly development and physiology have been recognized, how broadly these effects are observed across the Lactobacillus taxa remains largely unknown. In this study, four Lactobacillus species including five strains of L. plantarum were examined for their effects on fly larval development. Monoassociation of germ-free flies with L. rhamnosus (GG) most strongly accelerated fly larval development. Monoassociation with L. plantarum moderately accelerated fly development, but monoassociation with L. reuteri or L. sakei had marginal effects, despite similar bacterial loads in the host gut. An L. plantarum strain previously isolated from our lab rarely enhanced larval development, confirming the strain-specific effects of L. plantarum. The correlation between development-promoting effects and protein digestion activity in the host gut was found only among the members of L. plantarum species. Moreover, the cytoprotective response in the host gut known to be induced by L. plantarum was not correlated with development-promoting effects among any of the bacteria tested. Our results suggest that a broad range of Lactobacillus taxa are able to reside in the fly gut, but their ability to enhance host larval development is highly varied. This study may aid our understanding of the basic principles underlying the beneficial effects of probiotic commensal bacteria on metazoan development.

Steroid signaling mediates nutritional regulation of juvenile body growth via IGF-binding protein in Drosophila.

Nutritional condition during the juvenile growth period considerably affects final adult size. The insulin/insulin-like growth factor signaling (IIS)/target of rapamycin (TOR) nutrient-sensing pathway is known to regulate growth and metabolism in response to nutritional conditions. However, there is limited information on how endocrine pathways communicate nutritional information to different metabolic organs to regulate organismal growth. Here, we show that Imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor-binding protein 7 (IGFBP7), plays a key role in the nutritional control of organismal growth. Nutritional restriction during the larval growth period causes undersized adults, which is largely diminished by Imp-L2 mutation. We delineate a pathway in which nutritional restriction increases levels of the steroid hormone ecdysone, which, in turn, triggers ecdysone signaling-dependent Imp-L2 production from the fat body, a fly adipose organ, thereby attenuating peripheral IIS and body growth. Surprisingly, this endocrine pathway operates independent of the fat-body-TOR internal nutrient sensor, long believed to be the control center for nutrition-dependent growth. Our study reveals a previously unrecognized endocrine circuit mediating nutrition-dependent juvenile growth, which could also potentially be related to the insulin resistance frequently observed in puberty.

Comparative Analysis of Drosophila melanogaster Gut Microbiota with Respect to Host Strain, Sex, and Age.

Microbiota has a significant impact on the health of the host individual. The complexity of the interactions between mammalian hosts and their microbiota highlights the value of using Drosophila melanogaster as a model organism, because of its relatively simple microbial community and ease of physiological and genetic manipulation. However, highly variable and sometimes inconsistent results regarding the microbiota of D. melanogaster have been reported for host samples collected from different geographical locations; discrepancies that may be because of the inherent physiological conditions of the D. melanogaster host. Here, we conducted a comparative analysis of the gut microbiota of two D. melanogaster laboratory strains, w 1118 and Canton S, with respect to the sex and age of the host, by pyrosequencing of the 16S rRNA gene. In addition to the widespread and abundant commensal bacterial genera Lactobacillus and Acetobacter, we identified Enterococcus and Leuconostoc as major host-strain-specific bacterial genera. The relative proportions of these bacterial genera, and those of the species within each, were found to differ markedly with respect to strain, sex, and age of the host, even though host individuals were reared under the same nutritional conditions. By using various bioinformatic tools, we uncovered several characteristic features of microbiota corresponding to specific categories of the flies: host-sex-bias association of specific bacteria, age-dependent alteration of microbiota across host species and sex, and uniqueness of the microbiota of female w 1118 flies. Our results, thus, help to further our understanding of host-microbe interactions in the D. melanogaster model.

Torso, a Drosophila receptor tyrosine kinase, plays a novel role in the larval fat body in regulating insulin signaling and body growth.

Torso is a receptor tyrosine kinase whose localized activation at the termini of the Drosophila embryo is mediated by its ligand, Trunk. Recent studies have unveiled a second function of Torso in the larval prothoracic gland (PG) as the receptor for the prothoracicotropic hormone, which triggers pupariation. As such, inhibition of Torso in the PG prolongs the larval growth period, thereby increasing the final pupa size. Here, we report that Torso also acts in the larval fat body, regulating body size in a manner opposite from that of Torso in PG. We confirmed the expression of torso mRNA in the larval fat body and its reduction by RNA interference (RNAi). Fat body-specific knockdown of torso, by either of the two independent RNAi transgenes, significantly decreased the final pupal size. We found that torso knockdown suppresses insulin/target of rapamycin (TOR) signaling in the fat body, as confirmed by repression of Akt and S6K. Notably, the decrease in insulin/TOR signaling and decrease of pupal size induced by the knockdown of torso were rescued by the expression of a constitutively active form of the insulin receptor or by the knockdown of FOXO. Our study revealed a novel role for Torso in the fat body with respect to regulation of insulin/TOR signaling and body size. This finding exemplifies the contrasting effects of the same gene expressed in two different organs on organismal physiology.