Stable Host Gene Expression in the Gut of Adult Drosophila melanogaster with Different Bacterial Mono-Associations

Abstract

There is growing evidence that the microbes found in the digestive tracts of animals influence host biology, but we still do not understand how they accomplish this. Here, we evaluated how different microbial species commonly associated with laboratory-reared Drosophila melanogaster impact host biology at the level of gene expression in the dissected adult gut and in the entire adult organism. We observed that guts from animals associated from the embryonic stage with either zero, one or three bacterial species demonstrated indistinguishable transcriptional profiles. Additionally, we found that the gut transcriptional profiles of animals reared in the presence of the yeast Saccharomyces cerevisiae alone or in combination with bacteria could recapitulate those of conventionally-reared animals. In contrast, we found whole body transcriptional profiles of conventionally-reared animals were distinct from all of the treatments tested. Our data suggest that adult flies are insensitive to the ingestion of the bacteria found in their gut, but that prior to adulthood, different microbes impact the host in ways that lead to global transcriptional differences observable across the whole adult body.

How gut transcriptional function of Drosophila melanogaster varies with the presence and composition of the gut microbiota

“…Taken together, these data suggest that the Drosophila gut gene expression is responsive to the presence of microbes, but without a strong taxon-specific signal. Exceptionally, certain single strains of Acetobacter and Lactobacillus induce a very weak host transcriptional response (Elya et al, 2016), consistent with other studies demonstrating that some individual bacterial taxa do not significantly affect host traits (Chaston et al, 2014;.…”

“…Sex-specific host responses to microbiota perturbations have been reported in other animals (Human Microbiome Project Consortium, 2012;Jasarevic, Morrison, & Bale, 2016;Markle et al, 2013), but the underlying mechanisms are largely unknown. Interestingly, the genes and functional categories enriched in the gut transcriptome of Drosophila colonized with a standardized 5-member Acetobacter/Lactobacillus association (this study) overlap strongly with published studies on conventional flies (Broderick et al, 2014;Erkosar et al, 2014) and flies colonized with the yeast Saccharomyces cerevisiae (Elya et al, 2016). Taken together, these data suggest that the Drosophila gut gene expression is responsive to the presence of microbes, but without a strong taxon-specific signal.…”

“…Although the gut microbiota status of the animal can affect the gene expression of multiple organs (Clemente, Ursell, Parfrey, & Knight, 2012;Erkosar et al, 2013), the Drosophila gut displays more extensive responses than other organs to the gut microbiota (Dobson, Chaston, & Douglas, 2016), consistent with the proximity of the gut epithelium to the microbial cells in the gut lumen. Several studies have demonstrated substantial effects of eliminating the gut microbiota on gut gene expression in female Drosophila (Broderick et al, 2014;Elya et al, 2016;Erkosar et al, 2014). Our finding that axenic rearing has sex-specific effects on the gene expression profile of Drosophila (Figure 1) demonstrates that, although the microbiota composition does not generally differ between male and female Drosophila (Chandler et al, 2011;Wong, Ng, & Douglas, 2011), many of the genes with microbiota-dependent expression differ between the sexes.…”

“…Multiple studies comparing laboratory Drosophila with an un‐manipulated gut microbiota (conventional flies) and those experimentally deprived of their microbiota (axenic or germ‐free flies) concur that the gut microbiota is not essential for the host on nutrient‐sufficient diets, but that elimination of the microbiota alters many aspects of host metabolism, immune function, behaviour and cell signalling (Elgart et al., ; Jones et al., ; Ridley, Wong, Westmiller, & Douglas, ; Sharon et al., ; Shin et al., ; Storelli et al., ; Wong, Dobson, & Douglas, ). Furthermore, there is evidence that the taxonomic composition of the microbiota can influence host traits, including the gene expression profile of the gut and nutritional status of the insect (Broderick, Buchon, & Lemaitre, ; Elya, Zhang, Ludington, & Eisen, ; Erkosar et al., ; Newell & Douglas, ). By comparison, gut microbe–host interactions in field populations of Drosophila have received little study, beyond the demonstration of considerable variation in microbial community composition (Chandler et al., ; Wong et al., ; Staubach et al., ).…”

Gene regulatory mechanisms underlying the intestinal innate immune response

“…no, mild, or severe infection) on distinct, but constant genetic backgrounds through the use of inbred fly lines [56 ]. In addition, it is proving an ideal model to study the molecular and physiological role of the intestinal microbiota in post-embryonic development and homeostasis [57][58][59]. Finally, the Drosophila community has generated an extensive experimental toolkit including TF clone libraries [60] and TF overexpression fly lines [61], in vivo transgenic enhancer lines [62,63] as well as genome engineering tools such as CRISPR [64][65][66], rendering the Drosophila gut an ideal model to achieve a level of mechanistic, regulatory understanding that may currently be unattainable for the mammalian gastrointestinal tract.…”