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However, disease\u2010causing Na<jats:sub>v<\/jats:sub>channel mutations do not always result in severe symptoms, suggesting that the disease conditions are significantly affected by other genetic factors and various environmental exposures, collectively known as the \u201cexposome\u201d. Notably, recent research emphasizes the pivotal role of commensal bacteria in neural development and function. Although these bacteria typically benefit the nervous system under normal conditions, their impact during pathological states remains largely unknown. Here, we investigated the influence of commensal microbes on seizure\u2010like phenotypes exhibited by<jats:italic>para<\/jats:italic><jats:sup><jats:italic>Shu<\/jats:italic><\/jats:sup>\u2014a gain\u2010of\u2010function mutant of the<jats:italic>Drosophila<\/jats:italic>Na<jats:sub>v<\/jats:sub>channel gene,<jats:italic>paralytic<\/jats:italic>. Remarkably, the elimination of endogenous bacteria considerably ameliorated neurological impairments in<jats:italic>para<\/jats:italic><jats:sup><jats:italic>Shu<\/jats:italic><\/jats:sup>. Consistently, reintroducing bacteria, specifically from the<jats:italic>Lactobacillus<\/jats:italic>or<jats:italic>Acetobacter<\/jats:italic>genera, heightened the phenotypic severity in the bacteria\u2010deprived mutants. These findings posit that particular native bacteria contribute to the severity of seizure\u2010like phenotypes in<jats:italic>para<\/jats:italic><jats:sup><jats:italic>Shu<\/jats:italic><\/jats:sup>. We further uncovered that treating<jats:italic>para<\/jats:italic><jats:sup><jats:italic>Shu<\/jats:italic><\/jats:sup>with antibiotics boosted Nrf2 signaling in the gut, and that global Nrf2 activation mirrored the effects of removing bacteria from<jats:italic>para<\/jats:italic><jats:sup><jats:italic>Shu<\/jats:italic><\/jats:sup>. This raises the possibility that the removal of commensal bacteria suppresses the seizure\u2010like manifestations through augmented antioxidant responses. Since bacterial removal during development was critical for suppression of adult<jats:italic>para<\/jats:italic><jats:sup><jats:italic>Shu<\/jats:italic><\/jats:sup>phenotypes, our research sets the stage for subsequent studies, aiming to elucidate the interplay between commensal bacteria and the developing nervous system in conditions predisposed to the hyperexcitable nervous system.<\/jats:p>","DOI":"10.1111\/gbb.70000","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T17:47:26Z","timestamp":1725472046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Commensal bacteria exacerbate seizure\u2010like phenotypes in<scp><i>Drosophila<\/i><\/scp>voltage\u2010gated sodium channel mutants"],"prefix":"10.1111","volume":"23","author":[{"given":"Patrick","family":"Lansdon","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Genetics Graduate College, 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