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A previous study found that increasing nutrient availability promotes the activation of appendage regeneration. In this study, we found that changes in nutrient availability alter microbiome composition. Genome-scale metabolic modeling of the microbial symbionts suggests that the microbiome modulation reduces the abundance of a symbiont that competes with the host for metabolic resources. Antibiotic treatment that recapitulates the microbiome shift significantly promotes regeneration. Transcriptomic analysis of the host shows an upregulation of genes involved in the arginine biosynthetic pathway, including\n                    <jats:italic>argininosuccinate synthase<\/jats:italic>\n                    and\n                    <jats:italic>carbamoyl phosphate synthase<\/jats:italic>\n                    . Exogenous arginine supplementation promotes appendage regeneration. These findings suggest that microbiome composition, influenced by nutrient availability, contributes to the activation of host regeneration, and identify a role for arginine in promoting regeneration.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0355863","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:29:21Z","timestamp":1787333361000},"page":"e0355863","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiome modulation in regeneration in jellyfish"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4417-905X","authenticated-orcid":true,"given":"Aki","family":"Ohdera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0905-9672","authenticated-orcid":true,"given":"Matthew","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maille","family":"Mansbridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Ginn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"DeMerit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Guillen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Hyunsoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Notaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Herman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Goentoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"issue":"1","key":"pone.0355863.ref001","doi-asserted-by":"crossref","first-page":"16419","DOI":"10.1038\/s41598-017-16346-w","article-title":"Food availability drives plastic self-repair response in a basal metazoan- case study on the ctenophore Mnemiopsis leidyi A. 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