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The insect microbiome is known to play a key role in the degradation of organic substrates, but little is known about the metabolic potential of the microbiome of industrially reared fly larvae. We investigated the microbial composition and metabolic potential of the house fly (\n                      <jats:italic toggle=\"yes\">Musca domestica<\/jats:italic>\n                      ) larva gut microbiome from larvae grown on three different waste and by-product-based substrates. We found that bacteria associated with the larval gut were enriched for functions related to microbial stress mechanisms, indicating strong selection of the gut microbiome by house fly larvae. In addition, the gut microbiome of larvae reared on sludge-based substrate had higher diversity when weighting for rare species and a higher coverage of \u201ccarbohydrate transport and metabolism\u201d genes compared to brewery by-product-based substrate. A positive correlation between coverage of \u201cpyridoxal-P synthesis\u201d and larval survival and substrate conversion efficiency suggests that microbial synthesis of vitamin B\n                      <jats:sub>6<\/jats:sub>\n                      could enhance larval performance. Additionally, a negative correlation between coverage of the \u201cEntner-Doudoroff pathway\u201d and \u201chomoprotocatechuate degradation\u201d and substrate conversion indicates microbial competition for sugars and aromatic amino acids. Together, these results reveal how the host selects on gut microbiomes with metabolic potential that is optimized toward the conversion of substrates that may be ultimately valuable for commercial insect production.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Fly larvae are expected to play an important role in future food and feed production through the conversion of low-value biomass into high-quality protein. The gut microorganisms of fly larvae are expected to play an important role in bioconversion and could potentially be manipulated to improve biomass conversion. In this study, the importance of the gut bacteria of house fly larvae for bioconversion was investigated by metagenomic sequencing, which provided information on the bacterial abundance and potential functional roles in the larval gut. The results reveal that the functional potential of gut bacteria is affected by larval feed and correlates with larval performance, highlighting the importance of the gut microbiome for efficient biomass conversion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aem.00011-26","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:25:16Z","timestamp":1776097516000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Functional gut microbiomes enhance performance in house fly larvae"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0758-9994","authenticated-orcid":true,"given":"Asmus Toftk\u00e6r","family":"Muurmann","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04m5j1k67","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry and Bioscience, Aalborg University","place":["Aalborg, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7710-8912","authenticated-orcid":true,"given":"Jacob Agerbo","family":"Rasmussen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035b05819","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Evolutionary Hologenomics, University of Copenhagen","place":["K\u00f8benhavn, Denmark"]},{"name":"Cmbio","place":["K\u00f8benhavn, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-6531","authenticated-orcid":true,"given":"Morten T\u00f8nsberg","family":"Limborg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035b05819","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Evolutionary Hologenomics, University of Copenhagen","place":["K\u00f8benhavn, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-3963","authenticated-orcid":true,"given":"M. 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