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Both of these communities participate in essential aspects of host biology, including the immune response and interactions with pathogens. In recent years, our knowledge about the role of the insect microbiome in infection has increased tremendously. While many studies have highlighted the microbiome\u2019s protective effect against various natural enemies of insects, unexpected discoveries have shown that some members of the microbiota can facilitate pathogenic infections. Here, we summarize studies in the fruit fly,\n              <jats:italic toggle=\"yes\">Drosophila melanogaster<\/jats:italic>\n              , that have substantially progressed our understanding of host-pathogen-microbiome interactions during infection. We summarize studies on the protective mechanisms of\n              <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n              gut microbiota, highlight examples of microbiome exploitation by pathogens, and detail the mechanisms of endosymbiont-mediated host protection. In addition, we delve into a previously neglected topic in\n              <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n              microbiome research\u2014the crosstalk between endosymbionts and gut microbiota. Finally, we address how endosymbionts and gut microbiota remain resilient to host immune responses and stably colonize the host during infection. By examining how the microbiome is influenced by and reciprocally affects infection outcomes, this review provides timely and cohesive coverage of the roles of\n              <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n              endosymbionts and gut microbiota during infections.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00511-24","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T09:41:46Z","timestamp":1743759706000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["<i>Drosophila<\/i>\n            symbionts in infection: when a friend becomes an enemy"],"prefix":"10.1128","volume":"93","author":[{"given":"Yi","family":"Yu","sequence":"first","affiliation":[{"name":"Research Group Genetics of Host-Microbe Interactions, Max Planck Institute for Infection Biology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9249-8998","authenticated-orcid":true,"given":"Igor","family":"Iatsenko","sequence":"additional","affiliation":[{"name":"Research Group Genetics of Host-Microbe Interactions, Max Planck Institute for Infection Biology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.08.007"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.011"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2020.03.002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18849"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3182"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2608"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12567"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00007-19"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3535"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.4.767-772.1998"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0053-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.06.007"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.08.032"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15524"},{"key":"e_1_3_2_16_2","unstructured":"Microbiome diversity protects against pathogens by nutrient blocking. 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