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This review comprehensively examines the parallels and differences between these conditions, focusing on microbial signatures, inflammatory markers, and physiological features. Both diseases exhibit increased levels of Proteobacteria, decreased anaerobic short-chain fatty acid producers, and altered intestinal metabolic profiles. Common physiological characteristics include intestinal inflammation with elevated inflammatory markers (calprotectin, S100A12, lactoferrin), lower intestinal pH, and similar bile acid dysregulation patterns. However, key differences emerge in mucus characteristics, disease onset timing, and current treatment approaches. The gut microbiota plays a crucial role in both conditions, with shared signatures of dysbiosis suggesting similar intestinal environmental shifts and potential common therapeutic targets. Recent advances in CFTR modulator therapy have shown promising effects on the CF gut microbiome, while IBD treatments demonstrate variable efficacy. Understanding these similarities and differences is crucial for developing targeted therapies that could benefit both populations. This review highlights the complex interplay between host genetics, environmental factors, and the gut microbiota, emphasizing the need for further research to disentangle these relationships. We also discuss how the information provided here can be used to build and validate\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      models to study the dysbiotic microbial communities and their causes in these diseases, to develop more effective treatments.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00167-25","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T13:00:30Z","timestamp":1755522030000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Cystic fibrosis and inflammatory bowel disease: parallels in gut physiology and microbiota"],"prefix":"10.1128","volume":"207","author":[{"given":"Kaitlyn E.","family":"Barrack","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049s0rh22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Hanover, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2861-4392","authenticated-orcid":true,"given":"George A.","family":"O'Toole","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/049s0rh22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Hanover, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06244"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002533"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-020-01931-x"},{"key":"e_1_3_2_5_2","first-page":"17","article-title":"Part 1: the human gut microbiome in health and disease","volume":"13","author":"Bull MJ","year":"2014","unstructured":"Bull MJ, Plummer NT. 2014. 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