{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:03:13Z","timestamp":1788580993680,"version":"build-2803163510"},"reference-count":200,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Crohn's disease (CD) is an inflammatory bowel disease (IBD) sub-type characterized by transmural chronic inflammation of the gastrointestinal tract. Research indicates a complex CD etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. The chronic mucosal inflammation has been associated with a dysregulated state, or dysbiosis, of the gut microbiome (bacteria), mycobiome (fungi), virome (bacteriophages and viruses), and archeaome (archaea) further affecting the interkingdom syntrophic relationships and host metabolism. Microbiota dysbiosis in CD is largely described by an increase in facultative anaerobic pathobionts at the expense of strict anaerobic Firmicutes, such as\n                    <jats:italic>Faecalibacterium prausnitzii<\/jats:italic>\n                    . In the mycobiome, reduced fungal diversity and fungal-bacteria interactions, along with a significantly increased abundance of\n                    <jats:italic>Candida<\/jats:italic>\n                    spp. and a decrease in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    are well documented. Virome analysis also indicates a significant decrease in phage diversity, but an overall increase in phages infecting bacterial groups associated with intestinal inflammation. Finally, an increase in methanogenic archaea such as\n                    <jats:italic>Methanosphaera stadtmanae<\/jats:italic>\n                    exhibits high immunogenic potential and is associated with CD etiology. Common anti-inflammatory medications used in CD management (amino-salicylates, immunomodulators, and biologics) could also directly or indirectly affect the gut microbiome in CD. Other medications often used concomitantly in IBD, such as antibiotics, antidepressants, oral contraceptives, opioids, and proton pump inhibitors, have shown to alter the gut microbiota and account for increased susceptibility to disease onset or worsening of disease progression. In contrast, some environmental modifications through alternative therapies including fecal microbiota transplant (FMT), diet and dietary supplements with prebiotics, probiotics, and synbiotics have shown potential protective effects by reversing microbiota dysbiosis or by directly promoting beneficial microbes, together with minimal long-term adverse effects. In this review, we discuss the different approaches to modulating the global consortium of bacteria, fungi, viruses, and archaea in patients with CD through therapies that include antibiotics, probiotics, prebiotics, synbiotics, personalized diets, and FMT. We hope to provide evidence to encourage clinicians and researchers to incorporate these therapies into CD treatment options, along with making them aware of the limitations of these therapies, and indicate where more research is needed.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2022.887044","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T06:00:40Z","timestamp":1655359240000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Manipulation of Gut Microbiota as a Key Target for Crohn's Disease"],"prefix":"10.3389","volume":"9","author":[{"given":"Reem","family":"Rashed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosica","family":"Valcheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levinus A.","family":"Dieleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41572-020-0156-2","article-title":"Crohn's disease","volume":"6","author":"Roda","year":"2020","journal-title":"Nat Rev Dis Primers."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn's disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1053\/j.gastro.2010.06.070","article-title":"Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort","volume":"139","author":"Thia","year":"2010","journal-title":"Gastroenterology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1016\/j.cgh.2020.10.039","article-title":"Contemporary risk of surgery in patients with ulcerative colitis and Crohn's disease: a meta-analysis of population-based cohorts","volume":"19","author":"Tsai","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1093\/jcag\/gwy052","article-title":"The impact of inflammatory bowel disease in Canada 2018: a scientific report from the Canadian gastro-intestinal epidemiology consortium to Crohn's and colitis Canada","volume":"2","author":"Benchimol","year":"2019","journal-title":"J Can Assoc Gastroenterol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0016-5085(94)90066-3","article-title":"A shared and unique peptide in the human colon, eye, and joint detected by a monoclonal antibody","volume":"107","author":"Bhagat","year":"1994","journal-title":"Gastroenterology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1157\/13078423","article-title":"Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn's disease and ulcerative colitis","volume":"125","author":"Mendoza","year":"2005","journal-title":"Med Clin."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1097\/MIB.0000000000000392","article-title":"Extraintestinal manifestations of inflammatory bowel disease","volume":"21","author":"Vavricka","year":"2015","journal-title":"Inflamm Bowel Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/ajg.2010.343","article-title":"Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort","volume":"106","author":"Vavricka","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1159\/000341950","article-title":"Treatment of extraintestinal manifestations in inflammatory bowel disease","volume":"86","author":"Lakatos","year":"2012","journal-title":"Digestion."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1053\/j.gastro.2014.02.009","article-title":"The microbiome in inflammatory bowel disease: Current status and the future ahead","volume":"146","author":"Kostic","year":"2014","journal-title":"Gastroenterology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e01835","DOI":"10.3389\/fmicb.2018.01835","article-title":"The human gut microbiome - 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