{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:50:00Z","timestamp":1781578200107,"version":"3.54.5"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":57,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Research Council Future Fellowship","award":["FT160100126"],"award-info":[{"award-number":["FT160100126"]}]},{"name":"RMIT Vice Chancellor\u2019s Senior Research Fellowship","award":["APP1158952"],"award-info":[{"award-number":["APP1158952"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The intestinal mucus layer protects the host from invading pathogens and is essential for maintaining a healthy mucosal microbial community. Alterations in the mucus layer and composition of mucus-residing microbiota in people diagnosed with autism may contribute to dysbiosis and gastrointestinal dysfunction. Although microbial dysbiosis based on sequencing data is frequently reported in autism, spatial profiling of microbes adjacent to the mucosa is needed to identify changes in bacterial subtypes in close contact with host tissues. Here, we analysed the spatial distribution of the mucin-2 protein using immunofluorescence as well as total bacteria, Bacteroidetes, Firmicutes phyla, and Akkermansia muciniphila using fluorescent in situ hybridization in mice expressing the autism-associated R451C variant in the Neuroligin-3 gene. We show that the Neuroligin-3 R451C variant increases mucus density adjacent to the distal ileal epithelium in mice. The relative density of total bacteria, Firmicutes, and A. muciniphila was increased whereas the density of Bacteroidetes was decreased closer to the epithelium in Neuroligin-3R451C mice. In summary, the autism-associated R451C variant in the Neuroligin-3 gene increases mucus density adjacent to the epithelium and alters microbial spatial distribution in the mouse distal ileum.<\/jats:p>","DOI":"10.1093\/ismejo\/wraf037","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T21:10:54Z","timestamp":1741122654000},"source":"Crossref","is-referenced-by-count":4,"title":["Mice expressing the autism-associated neuroligin-3 R451C variant exhibit increased mucus density and altered distributions of intestinal microbiota"],"prefix":"10.1093","volume":"19","author":[{"given":"Madushani","family":"Herath","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, University of Melbourne , Grattan Street, Parkville, Victoria 3010 ,","place":["Australia"]},{"name":"Department of Pediatric Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston , Fannin Street, Houston, Texas 77030,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel C","family":"Bornstein","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, University of Melbourne , Grattan Street, Parkville, Victoria 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa L","family":"Hill-Yardin","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, University of Melbourne , Grattan Street, Parkville, Victoria 3010 ,","place":["Australia"]},{"name":"School of Health and Biomedical Sciences, STEM College, RMIT University , 225-245 Clements Drive, Bundoora, Victoria 3083 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1664-6060","authenticated-orcid":false,"given":"Ashley E","family":"Franks","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Anatomy Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University , Plenty Road, Bundoora, Victoria 3086 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"2025033006381271900_ref1","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1093\/glycob\/cwt040","article-title":"A refined palate: bacterial consumption of host glycans in the gut","volume":"23","author":"Marcobal","year":"2013","journal-title":"Glycobiology"},{"key":"2025033006381271900_ref2","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1542\/peds.2013-3995","article-title":"Gastrointestinal symptoms in autism spectrum disorder: a 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disorders","volume":"5","author":"Strati","year":"2017","journal-title":"Microbiome"},{"key":"2025033006381271900_ref6","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.physbeh.2014.10.033","article-title":"Gastrointestinal microbiota in children with autism in Slovakia","volume":"138","author":"Tomova","year":"2015","journal-title":"Physiol Behav"},{"key":"2025033006381271900_ref7","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1002\/aur.2127","article-title":"Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3","volume":"12","author":"Hosie","year":"2019","journal-title":"Autism Res"},{"key":"2025033006381271900_ref8","doi-asserted-by":"publisher","first-page":"12687","DOI":"10.1038\/s41598-023-39555-y","article-title":"Impaired cecal motility and secretion alongside expansion of gut-associated lymphoid tissue in the Nlgn3(R451C) mouse model of 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