{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:00:43Z","timestamp":1768525243703,"version":"3.49.0"},"posted":{"date-parts":[[2025,9,21]]},"group-title":"Genetics","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T00:00:00Z","timestamp":1758412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Endosomes are organelles that sort and traffic materials to different cellular compartments to enable performance of other organelles. One group of organelles supported by endosomes are lysosome related organelles (LROs) \u2013 which perform specialized functions using endocytosed or recycled materials from endosomes. LROs include melanosomes, lytic granules, platelet dense granules, lamellar bodies, and more. Individuals with endosome trafficking disorders commonly present with oculocutaneous albinism due to insufficient trafficking to \u2013 and maturation of \u2013 melanosomes. While the loss of pigment is an easily identifiable phenotype, mutations in endosome trafficking can also cause multi-organ system symptoms due to more broad disruption of LROs. Different endosome trafficking mutations impact LRO maturation at different degrees of severity and can impact a subset or all LROs leading to a wide range of symptomologies. Endosome trafficking disorders can present with oculocutaneous albinism (caused by mutated melanosomes), blood diathesis (caused by mutated platelet dense granules), pulmonary fibrosis (caused by mutated lamellar bodies), or chronic inflammation and inflammatory bowel disease (IBD) (caused by mutated lytic granules), as well as other symptoms. The shared inflammatory patterns of Hermansky-Pudlak Syndrome (HPS) and Inflammatory Bowel Disease (IBD) are well studied. However, impacts of this shared gastrointestinal inflammation on the gut microbiome remain unexplored. Using a spontaneously identified mutant family of threespine stickleback fish, we characterize changes in LROs and symptoms of oculocutaneous albinism. We further demonstrate that the shared gastrointestinal phenotypes of HPS and IBD extend to the gut microbiome showing similar shifts in microbial communities consistent with IBD. We argue endosome trafficking models should be explored as models to study the gut microbiome in addition to inflammatory phenotypes in IBD, and importantly, be used to test microbial\/dietary interventions for both IBD and endosome trafficking disorders.<\/jats:p>","DOI":"10.1101\/2025.09.20.677535","type":"posted-content","created":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T23:25:19Z","timestamp":1758497119000},"source":"Crossref","is-referenced-by-count":0,"title":["Spontaneous mutant in threespine stickleback connects endosome trafficking disorders and inflammatory bowel diseases via changes in the gut microbiome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9810-5094","authenticated-orcid":false,"given":"Emily A.","family":"Beck","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4143-4481","authenticated-orcid":false,"given":"Caitlin A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3688-7208","authenticated-orcid":false,"given":"Mark C.","family":"Currey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1615-7590","authenticated-orcid":false,"given":"Clayton M.","family":"Small","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2907-1016","authenticated-orcid":false,"given":"Brendan J. M.","family":"Bohannan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3496-8074","authenticated-orcid":false,"given":"William A.","family":"Cresko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025092505001077000_2025.09.20.677535v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00191-16"},{"key":"2025092505001077000_2025.09.20.677535v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003376"},{"key":"2025092505001077000_2025.09.20.677535v1.3","doi-asserted-by":"crossref","unstructured":"Barto\u0144, K. 2010.MuMIn: Multi-Model Inference.","DOI":"10.32614\/CRAN.package.MuMIn"},{"key":"2025092505001077000_2025.09.20.677535v1.4","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1534\/g3.119.400685","article-title":"QTL Mapping of Intestinal Neutrophil Variation in Threespine Stickleback Reveals Possible Gene Targets Connecting Intestinal Inflammation and Systemic Health","volume":"10","year":"2020","journal-title":"G3 Genes|Genomes|Genetics"},{"key":"2025092505001077000_2025.09.20.677535v1.5","doi-asserted-by":"publisher","DOI":"10.2307\/2346101"},{"key":"2025092505001077000_2025.09.20.677535v1.6","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0470-z"},{"key":"2025092505001077000_2025.09.20.677535v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2276"},{"key":"2025092505001077000_2025.09.20.677535v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0209-9"},{"key":"2025092505001077000_2025.09.20.677535v1.9","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12646"},{"key":"2025092505001077000_2025.09.20.677535v1.10","doi-asserted-by":"publisher","DOI":"10.2307\/1942268"},{"key":"2025092505001077000_2025.09.20.677535v1.11","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301595"},{"key":"2025092505001077000_2025.09.20.677535v1.12","first-page":"378","article-title":"glmmTMB Balances Speed and Flexibility Among Packages for Zero-inflated Generalized Linear Mixed Modeling","volume":"9","year":"2017","journal-title":"The R Journal"},{"key":"2025092505001077000_2025.09.20.677535v1.13","doi-asserted-by":"publisher","DOI":"10.1111\/mec.12354"},{"key":"2025092505001077000_2025.09.20.677535v1.14","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1534\/g3.111.000240","article-title":"Stacks : Building and Genotyping Loci De Novo From Short-Read Sequences","volume":"1","year":"2011","journal-title":"G3 Genes|Genomes|Genetics"},{"key":"2025092505001077000_2025.09.20.677535v1.15","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000051"},{"key":"2025092505001077000_2025.09.20.677535v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.037"},{"key":"2025092505001077000_2025.09.20.677535v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020109"},{"key":"2025092505001077000_2025.09.20.677535v1.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308479101"},{"key":"2025092505001077000_2025.09.20.677535v1.19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr330"},{"key":"2025092505001077000_2025.09.20.677535v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80170-7"},{"key":"2025092505001077000_2025.09.20.677535v1.21","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03006-05"},{"key":"2025092505001077000_2025.09.20.677535v1.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194193"},{"key":"2025092505001077000_2025.09.20.677535v1.23","first-page":"213","article-title":"Complicated granulomatous colitis in a patient with Hermansky-Pudlak syndrome, successfully treated with infliximab","volume":"69","year":"2006","journal-title":"Acta Gastroenterol Belg"},{"key":"2025092505001077000_2025.09.20.677535v1.24","doi-asserted-by":"crossref","unstructured":"Etter, P. D. , S. Bassham , P. A. Hohenlohe , E. A. Johnson , and W. A. Cresko . 2012. SNP Discovery and Genotyping for Evolutionary Genetics Using RAD Sequencing. Pp. 157\u2013178 in V. Orgogozo and M. V. Rockman , eds. Molecular Methods for Evolutionary Genetics. Humana Press, Totowa, NJ.","DOI":"10.1007\/978-1-61779-228-1_9"},{"key":"2025092505001077000_2025.09.20.677535v1.25","first-page":"e00145","article-title":"Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback","volume":"12","year":"2021","journal-title":"mBio"},{"key":"2025092505001077000_2025.09.20.677535v1.26","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1534\/g3.115.017905","article-title":"Genome Assembly Improvement and Mapping Convergently Evolved Skeletal Traits in Sticklebacks with Genotyping-by-Sequencing","volume":"5","year":"2015","journal-title":"G3 Genes|Genomes|Genetics"},{"key":"2025092505001077000_2025.09.20.677535v1.27","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1534\/g3.114.016519","article-title":"Genetic mapping of natural variation in schooling tendency in the threespine stickleback","volume":"5","year":"2015","journal-title":"G3 (Bethesda)"},{"key":"2025092505001077000_2025.09.20.677535v1.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1095-8649.2000.tb00490.x"},{"key":"2025092505001077000_2025.09.20.677535v1.29","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1111\/j.1572-0241.2006.00733.x","article-title":"Granulomatous Enterocolitis Associated with Hermansky-Pudlak Syndrome","volume":"101","year":"2006","journal-title":"Am J Gastroenterol"},{"key":"2025092505001077000_2025.09.20.677535v1.30","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1534\/g3.117.1125","article-title":"Sequence-Based Mapping and Genome Editing Reveal Mutations in Stickleback Hps5 Cause Oculocutaneous Albinism and the casper Phenotype","volume":"7","year":"2017","journal-title":"G3 Genes|Genomes|Genetics"},{"key":"2025092505001077000_2025.09.20.677535v1.31","doi-asserted-by":"crossref","unstructured":"Hartig, F. 2016.DHARMa: Residual Diagnostics for Hierarchical (Multi-Level \/ Mixed) Regression Models.","DOI":"10.32614\/CRAN.package.DHARMa"},{"key":"2025092505001077000_2025.09.20.677535v1.32","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1463-1318.2006.01046.x","article-title":"Crohn\u2019s-like colitis, enterocolitis and perianal disease in Hermansky\u2013Pudlak syndrome","volume":"8","year":"2006","journal-title":"Colorectal Disease"},{"key":"2025092505001077000_2025.09.20.677535v1.33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000862"},{"key":"2025092505001077000_2025.09.20.677535v1.34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.9.081307.164303"},{"key":"2025092505001077000_2025.09.20.677535v1.35","first-page":"550","article-title":"Hermansky-pudlak syndrome: report of a case and review of the literature","volume":"1","year":"2008","journal-title":"Int J Clin Exp Pathol"},{"key":"2025092505001077000_2025.09.20.677535v1.36","unstructured":"Introne, W. , M. Huizing , M. Malicdan , K. O\u2019Brien , and W. Gahl . 2023. Hermansky-Pudlak Syndrome. P. in Gene Reviews. University of Washington, University of Washington."},{"key":"2025092505001077000_2025.09.20.677535v1.37","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/pcmr.12504","article-title":"Simple chronic colitis model using hypopigmented mice with a Hermansky\u2013Pudlak syndrome 5 gene mutation","volume":"29","year":"2016","journal-title":"Pigment Cell Melanoma Res"},{"key":"2025092505001077000_2025.09.20.677535v1.38","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24025"},{"key":"2025092505001077000_2025.09.20.677535v1.39","unstructured":"Jovic, M. , M. Sharma , J. Rahajeng , and S. Caplan . 2009. The early endosome: a busy sorting station for proteins at the crossroads. Histology and Histopathology 99\u2013112."},{"key":"2025092505001077000_2025.09.20.677535v1.40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"2025092505001077000_2025.09.20.677535v1.41","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/1752-1947-1-176","article-title":"Complicated Crohn\u2019s-like colitis, associated with Hermansky-Pudlak syndrome, treated with Infliximab: a case report and brief review of the literature","volume":"1","year":"2007","journal-title":"J Med Case Rep"},{"key":"2025092505001077000_2025.09.20.677535v1.42","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.47719-0"},{"key":"2025092505001077000_2025.09.20.677535v1.43","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1016\/j.healun.2004.11.015","article-title":"Successful Bilateral Lung Transplantation for Pulmonary Fibrosis Associated With the Hermansky-Pudlak Syndrome","volume":"24","year":"2005","journal-title":"The Journal of Heart and Lung Transplantation"},{"key":"2025092505001077000_2025.09.20.677535v1.44","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0399-8320(06)73239-0","article-title":"Ileal Crohn\u2019s disease in a woman with Hermansky-Pudlak syndrome","volume":"30","year":"2006","journal-title":"Gastroent\u00e9rologie Clinique et Biologique"},{"key":"2025092505001077000_2025.09.20.677535v1.45","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"2025092505001077000_2025.09.20.677535v1.46","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00438-017-1302-8","article-title":"A deletion in the Hermansky\u2013Pudlak syndrome 4 (Hps4) gene appears to be responsible for albinism in channel catfish","volume":"292","year":"2017","journal-title":"Mol Genet Genomics"},{"key":"2025092505001077000_2025.09.20.677535v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2013.04.008"},{"key":"2025092505001077000_2025.09.20.677535v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-014-0454-4"},{"key":"2025092505001077000_2025.09.20.677535v1.49","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/ismej.2011.139","article-title":"An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea","volume":"6","year":"2012","journal-title":"The ISME Journal"},{"key":"2025092505001077000_2025.09.20.677535v1.50","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.021881"},{"key":"2025092505001077000_2025.09.20.677535v1.51","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1167\/iovs.15-17328","article-title":"Retinal Ganglion Cell and Inner Plexiform Layer Loss Correlate with Visual Acuity Loss in LHON: A Longitudinal, Segmentation OCT Analysis","volume":"57","year":"2016","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"2025092505001077000_2025.09.20.677535v1.52","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.216499"},{"key":"2025092505001077000_2025.09.20.677535v1.53","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/joim.13224","article-title":"Inflammatory bowel disease in Hermansky\u2013Pudlak syndrome: a retrospective single-centre cohort study","volume":"290","year":"2021","journal-title":"J Intern Med"},{"key":"2025092505001077000_2025.09.20.677535v1.54","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06090-z"},{"key":"2025092505001077000_2025.09.20.677535v1.55","doi-asserted-by":"crossref","unstructured":"Oksanen, J. , G. L. Simpson , F. G. Blanchet , R. Kindt , P. Legendre , P. R. Minchin , R. B. O\u2019Hara , P. Solymos , M. H. H. Stevens , E. Szoecs , H. Wagner , M. Barbour , M. Bedward , B. Bolker , D. Borcard , T. Borman , G. Carvalho , M. Chirico , M. De Caceres , S. Durand , H. B. A. Evangelista , R. FitzJohn , M. Friendly , B. Furneaux , G. Hannigan , M. O. Hill , L. Lahti , C. Martino , D. McGlinn , M.-H. Ouellette , E. Ribeiro Cunha , T. Smith , A. Stier , C. J. F. Ter Braak , and J. Weedon . 2001. vegan: Community Ecology Package.","DOI":"10.32614\/CRAN.package.vegan"},{"key":"2025092505001077000_2025.09.20.677535v1.56","first-page":"2825","article-title":"Scikit-learn: Machine learning in Python","volume":"12","year":"2011","journal-title":"Journal of Machine Learning Research"},{"key":"2025092505001077000_2025.09.20.677535v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.08.030"},{"key":"2025092505001077000_2025.09.20.677535v1.58","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12567"},{"key":"2025092505001077000_2025.09.20.677535v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/0022-5193(66)90013-0"},{"key":"2025092505001077000_2025.09.20.677535v1.60","doi-asserted-by":"crossref","unstructured":"Pinheiro, J. , D. Bates , and R Core Team. 1999.nlme: Linear and Nonlinear Mixed Effects Models.","DOI":"10.32614\/CRAN.package.nlme"},{"key":"2025092505001077000_2025.09.20.677535v1.61","doi-asserted-by":"crossref","unstructured":"Pinhero, J.C. and Bates, D.M . 2000. Mixed-Effects Models in S and S-PLUS. Springer-Verlag, New York.","DOI":"10.1007\/978-1-4419-0318-1"},{"key":"2025092505001077000_2025.09.20.677535v1.62","doi-asserted-by":"publisher","DOI":"10.1159\/000350954"},{"key":"2025092505001077000_2025.09.20.677535v1.63","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2258"},{"key":"2025092505001077000_2025.09.20.677535v1.64","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2019.1911"},{"key":"2025092505001077000_2025.09.20.677535v1.65","doi-asserted-by":"publisher","DOI":"10.1111\/mec.15253"},{"key":"2025092505001077000_2025.09.20.677535v1.66","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.2584"},{"key":"2025092505001077000_2025.09.20.677535v1.67","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-92-1-20"},{"key":"2025092505001077000_2025.09.20.677535v1.68","first-page":"e00219","article-title":"Host genomic variation shapes gut microbiome diversity in threespine stickleback fish","volume":"14","year":"2023","journal-title":"mBio"},{"key":"2025092505001077000_2025.09.20.677535v1.69","first-page":"e00331","article-title":"Highly Reproducible 16S Sequencing Facilitates Measurement of Host Genetic Influences on the Stickleback Gut Microbiome","volume":"4","year":"2019","journal-title":"mSystems"},{"key":"2025092505001077000_2025.09.20.677535v1.70","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evx014"},{"key":"2025092505001077000_2025.09.20.677535v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2015.64"},{"key":"2025092505001077000_2025.09.20.677535v1.72","doi-asserted-by":"publisher","DOI":"10.3390\/genes10070484"},{"key":"2025092505001077000_2025.09.20.677535v1.73","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3109\/13816819009020985","article-title":"The Hermansky-Pudlak syndrome: Variable reaction to 1-desamino-8D-arginine vasopressin for correction of the bleeding time","volume":"11","year":"1990","journal-title":"Ophthalmic Paediatrics and Genetics"},{"key":"2025092505001077000_2025.09.20.677535v1.74","doi-asserted-by":"crossref","first-page":"738420","DOI":"10.1016\/j.aquaculture.2022.738420","article-title":"Knockout of Hermansky-Pudlak Syndrome 4 (hps4) leads to silver-white tilapia lacking melanosomes","volume":"559","year":"2022","journal-title":"Aquaculture"},{"key":"2025092505001077000_2025.09.20.677535v1.75","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2005.00289.x"},{"key":"2025092505001077000_2025.09.20.677535v1.76","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12323"},{"key":"2025092505001077000_2025.09.20.677535v1.77","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000382"},{"key":"2025092505001077000_2025.09.20.677535v1.78","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq057"},{"key":"2025092505001077000_2025.09.20.677535v1.79","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0193-2020"},{"key":"2025092505001077000_2025.09.20.677535v1.80","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-020-03803-z"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.20.677535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:38:27Z","timestamp":1768469907000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.09.20.677535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,21]]},"references-count":80,"URL":"https:\/\/doi.org\/10.1101\/2025.09.20.677535","relation":{},"subject":[],"published":{"date-parts":[[2025,9,21]]},"subtype":"preprint"}}