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Failed host immune system-microbial interactions can result in a persistent inflammatory response in which the immune system indiscriminately attacks resident microbes, and at times the host cells themselves, leading to diseases such as Ulcerative Colitis, Crohn\u2019s Disease, and Psoriasis. Host genetic variation has been linked to both microbiome diversity and to severity of such inflammatory disease states in humans. However, the microbiome and inflammatory states manifest as quantitative traits, which encompass many genes interacting with one another and the environment. The mechanistic relationships among all of these interacting components are still not clear. Developing natural genetic models of host-microbe interactions is therefore fundamental to understanding the complex genetics of these and other diseases. Threespine stickleback (Gasterosteus aculeatus) fish are a tractable model for attacking this problem because of abundant population-level genetic and phenotypic variation in the gut inflammatory response. Previous work in our laboratory identified genetically divergent stickleback populations exhibiting differences in intestinal neutrophil activity. We took advantage of this diversity to genetically map variation in an emblematic element of gut inflammation - intestinal neutrophil recruitment - using an F2-intercross mapping framework. We identified two regions of the genome associated with increased intestinal inflammation containing several promising candidate genes. Within these regions we found candidates in the Coagulation\/Complement System, NFkB and MAPK pathways along with several genes associated with intestinal diseases and neurological diseases commonly accompanying intestinal inflammation as a secondary symptom. These findings highlight the utility of using naturally genetically diverse \u2018evolutionary mutant models\u2019 such as threespine stickleback to better understand interactions among host genetic diversity and microbiome variation in health and disease states.<\/jats:p>","DOI":"10.1534\/g3.119.400685","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T03:09:17Z","timestamp":1576552157000},"page":"613-622","source":"Crossref","is-referenced-by-count":8,"title":["QTL Mapping of Intestinal Neutrophil Variation in Threespine Stickleback Reveals Possible Gene Targets Connecting Intestinal Inflammation and Systemic Health"],"prefix":"10.1093","volume":"10","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\/0000-0003-3688-7208","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"}]},{"given":"William A","family":"Cresko","sequence":"additional","affiliation":[{"name":"Institute of Ecology and Evolution, University of Oregon, Eugene OR, 97403"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,2,1]]},"reference":[{"key":"2021042011071970100_bib1","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1053\/j.gastro.2014.01.058","article-title":"Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease.","volume":"146","author":"Albenberg","year":"2014","journal-title":"Gastroenterol."},{"key":"2021042011071970100_bib2","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.tig.2008.11.006","article-title":"Evolutionary mutant models for human disease.","volume":"25","author":"Albertson","year":"2009","journal-title":"Trends Genet."},{"key":"2021042011071970100_bib3","doi-asserted-by":"publisher","first-page":"322","DOI":"10.3389\/fmicb.2017.00322","article-title":"The Influence of Host Stress on the Mechanism of Infection: Lost Microbiomes, Emergent Pathobiomes, and the Role of Interkingdom Signaling.","volume":"8","author":"Alverdy","year":"2017","journal-title":"Front. 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