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They can parasitize diverse vertebrates and transmit a number of widespread infections. Once acquired from infected hosts, many tick\u2010borne pathogens, like <jats:italic>Borrelia burgdorferi<\/jats:italic>, are confined within the tick gut lumen and are surrounded by discrete gut barriers. Such barriers include the peritrophic membrane (PM) and the dityrosine network (DTN), which are in close contact with resident microbiota and invading pathogens, influencing their survival within the vector. Herein, we review our current state of knowledge about tick\u2013microbe interactions involving the PM and DTN structures. As a model, we will focus on <jats:italic>Ixodes<\/jats:italic> ticks, their microbiome, and the pathogen of Lyme disease. We will address the most salient findings on the structural and physiological roles of these <jats:italic>Ixodes<\/jats:italic> gut barriers on microbial interactions, with a comparison to analogous functions in other model vectors, such as mosquitoes. We will distill how this information could be leveraged towards a better understanding of the basic mechanisms of gut biology and tick\u2013microbial interactions, which could contribute to potential therapeutic strategies in response to ticks and tick\u2010borne infections.<\/jats:p>","DOI":"10.1111\/mmi.14822","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T21:37:11Z","timestamp":1632778631000},"page":"1241-1248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Tick gut barriers impacting tick\u2013microbe interactions and pathogen persistence"],"prefix":"10.1111","volume":"116","author":[{"given":"Chrysoula","family":"Kitsou","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine University of Maryland, College Park and Virginia\u2010Maryland Regional College of Veterinary Medicine College Park Maryland 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