{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:43:07Z","timestamp":1790023387879,"version":"4.0.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005421","name":"Guilan University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005421","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Studies have shown that changes in the frequency of oral microorganisms may play a key role in the development of Alzheimer's disease (AD). However, no research has been conducted on the oral fungal composition in AD-patients. The present study aimed to investigate the changes in the frequency of oral fungal composition, the antifungal susceptibility, and the enzymatic profiles of oral fungal composition in patients suffering from AD compared to non-AD individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>In the present analytical cross-sectional study during 12 months, 76 hospitalized patients with AD were matched with 76 individuals without AD. A sterile serum physiology-moistened cotton-tipped swab was used to sample the mouth area. All swabs were cultured on Sabouraud Chloramphenicol Agar. Fungal identified were confirmed through the PCR-sequencing techniques. Enzyme activity index (EAI) for important pathogenic factors including proteinase, esterase and hemolysin was measured using relevant protocols. The susceptibility to 8 antifungal agents (nystatin, voriconazole, itraconazole, fluconazole, posaconazole, amphotericin B, 5-fluorocytosine, and caspofungin) against fungal strains obtained from AD-patients was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A4 for yeasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that compared to the non-AD individuals, the prevalence of oral fungal composition in AD group was 1.6 times higher. <jats:italic>Candida albicans<\/jats:italic> was the most common fungal species isolated from oral swab samples of AD group (n=53, 80%) and non-AD group (n=28, 40%), and the diversity of the oral fungal composition in AD-patients were lower than non-AD individuals. Among the 3 investigated virulence factors, a statistically significant difference was shown in terms of hemolysin activity level between the two studied groups (<jats:italic>p<\/jats:italic>&amp;lt;0.05) and the activity level of esterase and proteinase enzymes did not show a significant difference in the two studied groups (<jats:italic>p<\/jats:italic>&amp;gt;0.05). The results showed that almost all of the tested isolates were susceptible to nystatin, the most widely prescribed antifungal to treat superficial infections, and only 1.69 % (2\/118) of the <jats:italic>Candida<\/jats:italic> isolates were resistant to this antifungal drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Understanding the changes in the frequency of oral fungal composition the antifungal susceptibility, and the enzymatic profiles of oral fungal composition in patients suffering from AD compared to non-AD individuals makes it possible to better understand the etiology of this disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1477230","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T05:10:36Z","timestamp":1729228236000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparing the frequency, antifungal susceptibility, and enzymatic profiles of the oral fungal composition in patients with and without Alzheimer's disease admitted to a neurology clinic"],"prefix":"10.3389","volume":"14","author":[{"given":"Mandana","family":"Golipoor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Rafat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia","family":"Saberi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davoud","family":"Roostaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir-Mohammad","family":"Shabanpour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.ijsu.2019.11.002","article-title":"STROCSS 2019 Guideline: strengthening the reporting of cohort studies in surgery","volume":"72","author":"Agha","year":"2019","journal-title":"Int. J. surge."},{"key":"B2","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3233\/JAD-2004-6507","article-title":"Reversible dementia: a case of cryptococcal meningitis masquerading as Alzheimer's disease","volume":"6","author":"Ala","year":"2004","journal-title":"J. Alzheimers Dis."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2021.699959","article-title":"Explain the experience of family caregivers regarding care of Alzheimer's patients: a qualitative study","volume":"12","author":"Ashrafizadeh","year":"2021","journal-title":"Front. Psychol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1097\/OPX.0000000000001652","article-title":"Evaluation of polymerase chain reaction over routine microbial diagnosis for the diagnosis of fungal keratitis","volume":"98","author":"Behera","year":"2021","journal-title":"Optom Vis. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/mBio.00218-19","article-title":"Serum amyloid P component binds fungal surface amyloid and decreases human macrophage phagocytosis and secretion of inflammatory cytokines","volume":"10","author":"Behrens","year":"2019","journal-title":"MBio"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.3390\/antiox10091353","article-title":"Role of oxidative damage in Alzheimer\u2019s disease and neurodegeneration: From pathogenic mechanisms to biomarker discovery","volume":"10","author":"Buccellato","year":"2021","journal-title":"Antioxidants"},{"key":"B7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/myc.12695","article-title":"Prevalence, virulence factors and antifungal susceptibility of Candida spp. isolated from bloodstream infections in a tertiary care hospital in Brazil","volume":"61","author":"Canela","year":"2018","journal-title":"Mycoses"},{"key":"B8","doi-asserted-by":"publisher","first-page":"576","DOI":"10.3390\/medicina58050576","article-title":"Prevalence and antifungal susceptibility profile of oral Candida spp. Isolates from a Hospital in Slovakia","volume":"58","author":"\u010cern\u00e1kov\u00e1","year":"2022","journal-title":"Medicina"},{"key":"B9","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1089\/ars.2020.8076","article-title":"Inflammation in neurological disorders: the thin boundary between brain and periphery","volume":"33","author":"Cervellati","year":"2020","journal-title":"Antioxid. Redox Signaling"},{"key":"B10","volume-title":"Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi","year":"2008"},{"key":"B11","volume-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts","year":"2017"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2173544","DOI":"10.1080\/20002297.2023.2173544","article-title":"Oral microbiome in older adults with mild cognitive impairment","volume":"15","author":"Da","year":"2023","journal-title":"J. Oral. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s40292-020-00392-z","article-title":"Periodontitis and hypertension: is the association causal","volume":"27","author":"Del Pinto","year":"2020","journal-title":"High Blood Pressure Cardiovasc. Prev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/S1474-4422(07)70178-3","article-title":"Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS\u2013ADRDA criteria","volume":"6","author":"Dubois","year":"2007","journal-title":"Lancet Neurol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"7086512","DOI":"10.1155\/2021\/7086512","article-title":"Oxidative stress, neuroinflammation, and NADPH oxidase: implications in the pathogenesis and treatment of Alzheimer\u2019s disease","volume":"2021","author":"Ganguly","year":"2021","journal-title":"Oxid. Med. Cell. Long."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000713","article-title":"Characterization of the oral fungal microbiome (mycobiome) in healthy individuals","volume":"6","author":"Ghannoum","year":"2010","journal-title":"PloS pathog."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1007\/s10482-020-01474-7","article-title":"Human gut microbiota\/microbiome in health and diseases: a review","volume":"113","author":"Gomaa","year":"2020","journal-title":"Antonie Van Leeuwenhoek."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.693522","article-title":"A mycological and molecular epidemiologic study on onychomycosis and determination in vitro susceptibilities of isolated fungal strains to conventional and new antifungals","volume":"11","author":"Halvaee","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3233\/JAD-2009-0985","article-title":"Cryptococcal meningitis misdiagnosed as Alzheimer's disease: complete neurological and cognitive recovery with treatment","volume":"16","author":"Hoffmann","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/antiox10020253","article-title":"Carbonyl stress in red blood cells and hemoglobin","volume":"10","author":"Kosmachevskaya","year":"2021","journal-title":"Antioxidants"},{"key":"B21","doi-asserted-by":"publisher","first-page":"173","DOI":"10.29011\/2574-7347.100073","article-title":"Denture plaque management of denture-related stomatitis","volume":"6","author":"Le Bars","year":"2021","journal-title":"Dent. Adv. Res."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.895537","article-title":"The oral microbiota: community composition, influencing factors, pathogenesis, and interventions","volume":"13","author":"Li","year":"2022","journal-title":"Front. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41577-022-00826-w","article-title":"Immune responses to human fungal pathogens and therapeutic prospects","volume":"23","author":"Lionakis","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2971","DOI":"10.1128\/JCM.39.8.2971-2974.2001","article-title":"Candida species exhibit differential in vitro hemolytic activities","volume":"39","author":"Luo","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1007\/s10096-020-03912-w","article-title":"Mechanism of Candida pathogenesis: revisiting the vital drivers","volume":"39","author":"Mba","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"195","DOI":"10.21608\/aunj.2023.202022.1047","article-title":"Mycobiota associated with teeth and oral cavity and their relevant to dental and periodontal diseases","volume":"52","author":"Nasr","year":"2023","journal-title":"Assiut Univ. J. Multidiscip. Sci. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3390\/biomedicines9050524","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"9","author":"Onyango","year":"2021","journal-title":"Biomedicines"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.1128\/JCM.00937-12","article-title":"Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012","volume":"50","author":"Pfaller","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1111\/ejn.15599","article-title":"A closer look at the mycobiome in Alzheimer's disease: fungal species, pathogenesis and transmission","volume":"55","author":"Phuna","year":"2022","journal-title":"Eur. J. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1080\/00207454.2022.2045290","article-title":"A reappraisal on amyloid cascade hypothesis: The role of chronic infection in Alzheimer\u2019s disease","volume":"133","author":"Phuna","year":"2023","journal-title":"Int. J. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/j.csbj.2021.02.010","article-title":"The oralome and its dysbiosis: New insights into oral microbiome-host interactions","volume":"19","author":"Radaic","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.3390\/life12111677","article-title":"Nystatin effectiveness in Oral candidiasis treatment: a Systematic Review & Meta-Analysis of clinical trials","volume":"12","author":"Rai","year":"2022","journal-title":"Life"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.1097\/MS9.0000000000001956","article-title":"Assessment of species distribution and virulence factors of oral fungal carriage among hospitalized patients with COVID-19: a case-control study","volume":"86","author":"Ramezanalipour","year":"2024","journal-title":"Ann. Med. Surge."},{"key":"B34","first-page":"661","article-title":"Global deterioration scale (GDS)","volume":"24","author":"Reisberg","year":"1994","journal-title":"Psychopharmacol. bullet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"4456","DOI":"10.1016\/j.csbj.2023.08.030","article-title":"Stability of human gut microbiome: Comparison of ecological modelling and observational approaches","volume":"21","author":"Revel-Muroz","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/prd.12393","article-title":"The oral microbiome: Role of key organisms and complex networks in oral health and disease","volume":"87","author":"Sedghi","year":"2021","journal-title":"Periodontol. 2000."},{"key":"B37","doi-asserted-by":"publisher","first-page":"4626","DOI":"10.1128\/JCM.38.12.4626-4628.2000","article-title":"Tween 80 opacity test responses of various Candida species","volume":"38","author":"Slifkin","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"114969","DOI":"10.1016\/j.addr.2023.114969","article-title":"Reviving the interest in the versatile drug nystatin: A multitude of strategies to increase its potential as an effective and safe antifungal agent","volume":"199","author":"Sousa","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B39","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/BF02129881","article-title":"Proteolysis and pathogenicity of Candida albicans strains","volume":"37","author":"Staib","year":"1969","journal-title":"Mycopathol. Mycol. Appl."},{"key":"B40","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/s40120-022-00338-8","article-title":"Alzheimer\u2019s disease: epidemiology and clinical progression","volume":"11","author":"Tahami Monfared","year":"2022","journal-title":"Neurol. Ther."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1182\/blood.2022015596","article-title":"Hemolysis, free hemoglobin toxicity, and scavenger protein therapeutics","volume":"140","author":"Vallelian","year":"2022","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.3390\/biomedicines11041063","article-title":"Antifungal drug resistance: an emergent health threat","volume":"11","author":"Vitiello","year":"2023","journal-title":"Biomedicines"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.796867","article-title":"The impact of systemic inflammation on Alzheimer\u2019s disease pathology","volume":"12","author":"Xie","year":"2022","journal-title":"Front. Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/geroni\/igac059.002","article-title":"Fungal infections, use of antifungal agents, and the risk of Alzheimer\u2019s disease","volume":"6","author":"Yashkin","year":"2022","journal-title":"Innovation Aging."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1477230\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T05:10:39Z","timestamp":1729228239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1477230\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,18]]},"references-count":44,"alternative-id":["10.3389\/fcimb.2024.1477230"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2024.1477230","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,18]]},"article-number":"1477230"}}