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Animal models with <jats:italic>CHD7<\/jats:italic> gene variants demonstrate abnormal gut innovation and dysmotility. Our pilot study evaluated whether individuals with CHARGE syndrome have differences in their gut microbiome compared to unaffected siblings. Participants between the ages of 2\u201318 were recruited from Atlantic Canada with a confirmed genetic diagnosis of CHARGE syndrome. Gut Microbiome DNA analysis was performed on stool samples using 16S ribosomal RNA (rRNA) gene sequences. The PASSFP and PEDSQL served as GI symptom questionnaires. Eleven participants completed this study with one twin pair (CHARGE syndrome\u2009=\u20097, sibling controls\u2009=\u20094). The mean percent abundance for the four most common phyla in individuals with CHARGE versus Controls showed a trend towards increased Bacteroidetes, Proteobacteria, and a decrease in Firmicutes and Actinobacteria but was not significant. Microbiome comparisons based on abnormal (&lt;\u200977) and normal (\u200977) GI scores, found significantly elevated Bacteroidetes (<jats:italic>p<\/jats:italic>\u2009=\u20090.042, 59.5%\u2009\u00b1\u200915.1% vs. 33.1%\u2009\u00b1\u200914.6%) and decreased Firmicutes (<jats:italic>p<\/jats:italic>\u2009=\u20090.042, 37.5%\u2009\u00b1\u200915.9% vs. 62.4%\u2009\u00b1\u200914.0%) with abnormal scores. Alpha diversity did not differ with either disease or GI symptom scores. Our data showed that, although there was a trend in changes in the gut microbiome in individuals with CHARGE compared to unaffected siblings, this change appears to be related to the severity of GI symptoms and not necessarily CHARGE itself, as differences were more pronounced in individuals with more difficulties with feeding and GI symptoms.<\/jats:p>","DOI":"10.1002\/ajmg.a.64053","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T01:41:46Z","timestamp":1743817306000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut Microbiome Pilot Study of Patients With <scp>CHARGE<\/scp> Syndrome and Sibling Controls"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0213-6668","authenticated-orcid":false,"given":"Emily R.","family":"Chedrawe","sequence":"first","affiliation":[{"name":"Faculty of Medicine Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Connors","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology IWK Health  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6834-7780","authenticated-orcid":false,"given":"Angela","family":"Arra","sequence":"additional","affiliation":[{"name":"IWK Health  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Biology Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"van Limbergen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Amsterdam University Medical Centre  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00191\u201016"},{"key":"e_1_2_10_3_1","unstructured":"Blake K.2024.\u201cDr. Kim Blake. 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