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We have investigated the role of dietary fat in the pathogenesis of <jats:italic>Giardia<\/jats:italic> infection. Male 3 to 4-week-old C57BL\/6 mice were fed either a low fat (LF) or a high fat (HF) diet for 12\u00a0days and challenged with <jats:italic>G. duodenalis<\/jats:italic>. In infected animals, the trophozoite burden was higher in HF\u2009+\u2009<jats:italic>Giardia<\/jats:italic> mice compared to the LF\u2009+\u2009<jats:italic>Giardia<\/jats:italic> group at day 7 post infection. Fatty acids exerted direct pro-growth effects on <jats:italic>Giardia<\/jats:italic> trophozoites. Analysis of disease parameters showed that HF\u2009+\u2009<jats:italic>Giardia<\/jats:italic> mice exhibited more mucosal infiltration by inflammatory cells, decreased villus\/crypt ratios, goblet cell hyperplasia, mucus disruption, increased gut motility, and elevated fecal water content compared with LF\u2009+\u2009<jats:italic>Giardia<\/jats:italic>. HF diet-dependent exacerbation of <jats:italic>Giardia<\/jats:italic>-induced goblet cell hyperplasia was associated with elevated <jats:italic>Atoh1<\/jats:italic> and <jats:italic>Muc2<\/jats:italic> gene expression. Gut microbiota analysis revealed that the HF diet alone induces a taxonomic shift. HF\u2009+\u2009<jats:italic>Giardia<\/jats:italic> mice exhibited microbiota dysbiosis characterized by an increase of Firmicutes and a decrease of Bacteroidetes and significant changes in \u03b1- and \u03b2-diversity metrics. Taken together, the findings suggest that a HF diet exacerbates the outcome of <jats:italic>Giardia<\/jats:italic> infection. The data demonstrate that elevated dietary fat represents an important exogenous factor promoting the pathophysiology of giardiasis.<\/jats:p>","DOI":"10.1038\/s41598-021-98262-8","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T10:03:10Z","timestamp":1632304990000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis"],"prefix":"10.1038","volume":"11","author":[{"given":"Thibault","family":"Allain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Fekete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Sosnowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Desmonts de Lamache","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Motta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezirae","family":"Leger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Feener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raylene A.","family":"Reimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 G.","family":"Buret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"98262_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nrmicro2317","volume":"8","author":"J Ankarklev","year":"2010","unstructured":"Ankarklev, J., Jerlstrom-Hultqvist, J., Ringqvist, E., Troell, K. & Svard, S. 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