{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:35:03Z","timestamp":1760060103230,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MPs"],"abstract":"<jats:p>Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota\u2013gut\u2013brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut\u2013brain interactions.<\/jats:p>","DOI":"10.3390\/mps8040083","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T15:09:53Z","timestamp":1754492993000},"page":"83","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Faecal Microbiota Transplantation on Cognitive Function in Cognitively Healthy Adults with Irritable Bowel Syndrome: Protocol for a Randomised, Placebo-Controlled, Double-Blinded Pilot Study"],"prefix":"10.3390","volume":"8","author":[{"given":"Sara","family":"Alaeddin","sequence":"first","affiliation":[{"name":"School of Medicine, Western Sydney University, Penrith 2751, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanna","family":"Ko","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Penrith 2751, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8708-6104","authenticated-orcid":false,"given":"Genevieve Z.","family":"Steiner-Lim","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute and Translational Health Research Institute (THRI), Western Sydney University, Westmead 2145, Australia"},{"name":"Department of Psychiatry and Psychotherapy, Jena University Hospital, 07743 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slade O.","family":"Jensen","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Penrith 2751, Australia"},{"name":"Ingham Institute of Applied Medical Research, Liverpool 2170, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9266-0943","authenticated-orcid":false,"given":"Tara L.","family":"Roberts","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Penrith 2751, Australia"},{"name":"Ingham Institute of Applied Medical Research, Liverpool 2170, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-2933","authenticated-orcid":false,"given":"Vincent","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Medicine, Western Sydney University, Penrith 2751, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1854640","DOI":"10.1080\/19490976.2020.1854640","article-title":"Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than clostridium difficile infection: A systematic review and meta-analysis","volume":"12","author":"Green","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jemimah, S., Chabib, C.M.M., Hadjileontiadis, L., and AlShehhi, A. (2023). Gut microbiome dysbiosis in alzheimer\u2019s disease and mild cognitive impairment: A systematic review and meta-analysis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0285346"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1756284820946904","DOI":"10.1177\/1756284820946904","article-title":"Mechanisms underpinning the efficacy of faecal microbiota transplantation in treating gastrointestinal disease","volume":"13","author":"Segal","year":"2020","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chen, X., Zhang, W., Lin, Z., Zheng, C., Chen, S., Zhou, H., and Liu, Z. (2023). Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1103189"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2284247","DOI":"10.1080\/19490976.2023.2284247","article-title":"Efficacy of fecal microbiota transplantation in patients with parkinson\u2019s disease: Clinical trial results from a randomized, placebo-controlled design","volume":"15","author":"Cheng","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6449","DOI":"10.18632\/aging.204230","article-title":"Fecal microbiota transplantation can improve cognition in patients with cognitive decline and clostridioides difficile infection","volume":"14","author":"Park","year":"2022","journal-title":"Aging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1002\/hep.31496","article-title":"A randomized clinical trial of fecal microbiota transplant for alcohol use disorder","volume":"73","author":"Bajaj","year":"2021","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e133410","DOI":"10.1172\/jci.insight.133410","article-title":"Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis","volume":"4","author":"Bajaj","year":"2019","journal-title":"JCI Insight"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shi, S., Zhang, Q., Sang, Y.-X., Ge, S., Wang, Q., Wang, R., and He, J. (2022). Probiotic bifidobacterium longum bb68s improves cognitive functions in healthy older adults: A randomized, double-blind, placebo-controlled trial. Nutrients, 15.","DOI":"10.3390\/nu15010051"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.jff.2014.07.007","article-title":"Fermented milk of lactobacillus helveticus idcc3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults","volume":"10","author":"Chung","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7929","DOI":"10.1080\/10408398.2021.1920884","article-title":"Short-chain fatty acids-producing probiotics: A novel source of psychobiotics","volume":"62","author":"Cheng","year":"2021","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mirzaei, R., Bouzari, B., Hosseini-Fard, S.R., Mazaheri, M., Ahmadyousefi, Y., Abdi, M., Jalalifar, S., Karimitabar, Z., Teimoori, A., and Keyvani, H. (2021). Role of microbiota-derived short-chain fatty acids in nervous system disorders. Biomed. Pharmacother., 139.","DOI":"10.1016\/j.biopha.2021.111661"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e14200","DOI":"10.1111\/nmo.14200","article-title":"Long-term effects of fecal microbiota transplantation (fmt) in patients with irritable bowel syndrome","volume":"34","author":"Kristoffersen","year":"2022","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Schwarcz, R., Foo, A., Sathyasaikumar, K., and Notarangelo, F. (2024). The probiotic lactobacillus reuteri preferentially synthesizes kynurenic acid from kynurenine. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073679"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bbi.2018.10.003","article-title":"The kynurenine pathway and cognitive performance in community-dwelling older adults. The hordaland health study","volume":"75","author":"Solvang","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/advances\/nmz127","article-title":"Tryptophan metabolism: A link between the gut microbiota and brain","volume":"11","author":"Gao","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.clinthera.2015.03.002","article-title":"Gut microbiota: The conductor in the orchestra of immune\u2013neuroendocrine communication","volume":"37","author":"Dinan","year":"2015","journal-title":"Clin. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Campbell, B.M., Charych, E., Lee, A.W., and M\u00f6ller, T. (2014). Kynurenines in cns disease: Regulation by inflammatory cytokines. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00012"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2020.12.026","article-title":"Prebiotic and probiotic supplementation and the tryptophan-kynurenine pathway: A systematic review and meta analysis","volume":"123","author":"Purton","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.18632\/aging.101464","article-title":"Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice","volume":"10","author":"Zhan","year":"2018","journal-title":"Aging"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Parker, A., Romano, S., Ansorge, R., Aboelnour, A., Le Gall, G., Savva, G.M., Pontifex, M.G., Telatin, A., Baker, D., and Jones, E. (2022). Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain. Microbiome, 10.","DOI":"10.1186\/s40168-022-01243-w"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Elangovan, S., Borody, T.J., and Holsinger, R.M.D. (2022). Fecal microbiota transplantation reduces pathology and improves cognition in a mouse model of alzheimer\u2019s disease. Cells, 12.","DOI":"10.3390\/cells12010119"},{"key":"ref_24","unstructured":"Alaeddin, S., and Steiner-Lim, G.Z.S. (2025). Effect of Fmt on Systemic Circulation Markers, BioRender. Available online: https:\/\/BioRender.com\/0a408uy."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.3748\/wjg.v27.i39.6715","article-title":"Microbiota shaping\u2014The effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review","volume":"27","author":"Baldi","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1080\/1028415X.2024.2425570","article-title":"The impact of a prebiotic-rich diet and\/or probiotic supplements on human cognition: Secondary outcomes from the \u2018gut feelings\u2019 randomised controlled trial","volume":"28","author":"Freijy","year":"2025","journal-title":"Nutr. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.chom.2022.01.013","article-title":"Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans","volume":"30","author":"Puig","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nagpal, R., Neth, B.J., Wang, S., Mishra, S.P., Craft, S., and Yadav, H. (2020). Gut mycobiome and its interaction with diet, gut bacteria and alzheimer\u2019s disease markers in subjects with mild cognitive impairment: A pilot study. EBioMedicine, 59.","DOI":"10.1016\/j.ebiom.2020.102950"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1053\/j.gastro.2021.02.013","article-title":"Functional restoration of bacteriomes and viromes by fecal microbiota transplantation","volume":"160","author":"Fujimoto","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_30","first-page":"486","article-title":"Probiotics drive gut microbiome triggering emotional brain signatures","volume":"9","author":"Bagga","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1053\/j.gastro.2016.03.035","article-title":"Rome iv\u2014Functional gi disorders: Disorders of gut-brain interaction","volume":"150","author":"Drossman","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/jgh.13695","article-title":"Use of the low-fodmap diet in inflammatory bowel disease","volume":"32","author":"Gibson","year":"2017","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1136\/flgastro-2019-101298","article-title":"Best management of irritable bowel syndrome","volume":"12","author":"Black","year":"2021","journal-title":"Frontline Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Altobelli, E., Del Negro, V., Angeletti, P.M., and Latella, G. (2017). Low-fodmap diet improves irritable bowel syndrome symptoms: A meta-analysis. Nutrients, 9.","DOI":"10.3390\/nu9090940"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s12664-020-01122-y","article-title":"Cognitive dysfunction in ulcerative colitis patients in remission and its comparison with patients with irritable bowel syndrome and healthy controls","volume":"40","author":"Sharma","year":"2021","journal-title":"Indian J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1136\/gutjnl-2019-319630","article-title":"Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study","volume":"69","author":"Hatlebakk","year":"2020","journal-title":"Gut"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jhin.2017.05.004","article-title":"Comparative effectiveness of faecal microbiota transplant by route of administration","volume":"96","author":"Gundacker","year":"2017","journal-title":"J. Hosp. Infect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5480961","DOI":"10.1155\/2018\/5480961","article-title":"The value of fecal microbiota transplantation in the treatment of ulcerative colitis patients: A systematic review and meta-analysis","volume":"2018","author":"Cao","year":"2018","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104954","DOI":"10.1016\/j.phrs.2020.104954","article-title":"Delivery routes for faecal microbiota transplants: Available, anticipated and aspired","volume":"159","author":"Gulati","year":"2020","journal-title":"Pharmacol. 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