{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:43:12Z","timestamp":1785771792095,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sunstar, Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background and Objective: The oral microbiome plays an important role in oral health and disease, including periodontitis, which affects about 40% of the adult population in the United States. Bacterial pathogens have been well studied and documented in their relationship with periodontitis; however, the role of fungi in periodontitis is still unclear. The purpose of this study is to determine the relationship of specific fungal species with periodontal pathogenic bacteria in healthy, mild periodontitis, and severe periodontitis patients. Methods: In this study, human participants were recruited, and saliva samples were collected. Twelve participants representing periodontal health (n = 2), mild periodontitis (n = 3), and severe periodontitis (n = 7) were included. Salivary samples were sequenced for analysis of their mycobiome (ITS sequencing) and microbiome (16s RNA sequencing). Results: A total of 375 species of bacteria and 39 species of fungi were identified among all samples. Clustering was observed for bacteria in healthy and mild periodontitis, but more variability was observed in the severe periodontal disease group. Variability was observed for fungi among all samples and groups. Red complex bacteria were negatively correlated with Candida species for the disease groups, although the correlation was not statistically significant. A significant correlation was observed between red-complex bacteria in the severe periodontal disease group. Additionally, a significant correlation was observed among Candida species in all groups. Conclusions: This pilot study simultaneously processed saliva samples for microbiome and mycobiome sequencing and found a trend towards negative correlation between Candida species and red complex bacteria.<\/jats:p>","DOI":"10.3390\/jcm14186418","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T15:10:46Z","timestamp":1757603446000},"page":"6418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Correlation Between Fungal and Bacterial Populations in Periodontitis Through Targeted Sequencing: A Pilot Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Jacob","family":"Ayers","sequence":"first","affiliation":[{"name":"Division of Regenerative Sciences and Periodontics, Department of Advanced Specialty Sciences, James B Edwards College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Chinnici","sequence":"additional","affiliation":[{"name":"Roswell Park Cancer Center, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-837X","authenticated-orcid":false,"given":"Amarpreet","family":"Sabharwal","sequence":"additional","affiliation":[{"name":"Division of Periodontics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8591-4140","authenticated-orcid":false,"given":"Pinar","family":"Emecen-Huja","sequence":"additional","affiliation":[{"name":"Division of Regenerative Sciences and Periodontics, Department of Advanced Specialty Sciences, James B Edwards College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Hong","family":"Chien","sequence":"additional","affiliation":[{"name":"Division of Regenerative Sciences and Periodontics, Department of Advanced Specialty Sciences, James B Edwards College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpi","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Periodontics, School of Dental Medicine, University at Buffalo, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhiram","family":"Maddi","sequence":"additional","affiliation":[{"name":"Division of Regenerative Sciences and Periodontics, Department of Advanced Specialty Sciences, James B Edwards College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"},{"name":"Department of Periodontics, School of Dental Medicine, University at Buffalo, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.adaj.2018.04.023","article-title":"Periodontitis in U.S. adults: National Health and Nutrition Examination Survey 2009\u20132014","volume":"149","author":"Eke","year":"2018","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"641","DOI":"10.15585\/mmwr.mm6921a1","article-title":"Prevalence of and changes in tooth loss among adults aged \u226550 years with selected chronic conditions\u2014United States, 1999\u20132004 and 2011\u20132016","volume":"69","author":"Parker","year":"2020","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/jcpe.12808","article-title":"Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines","volume":"45","author":"Sanz","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_4","first-page":"CD004714","article-title":"Treatment of periodontitis for glycaemic control in people with diabetes mellitus","volume":"4","author":"Simpson","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s13238-018-0548-1","article-title":"Oral microbiomes: More and more importance in oral cavity and whole body","volume":"9","author":"Gao","year":"2018","journal-title":"Protein Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.1016\/j.cell.2022.09.015","article-title":"A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors","volume":"185","author":"Dohlman","year":"2022","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S173","DOI":"10.1002\/JPER.17-0721","article-title":"Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop","volume":"89","author":"Papapanou","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1399-302X.1992.tb00519.x","article-title":"Bacterial synergy of Treponema denticola and Porphyromonas gingivalis","volume":"7","author":"Simonson","year":"1992","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mulla, M., Mulla, M., Hegde, S., and Koshy, A.V. (2021). In vitro assessment of probiotic Lactobacillus reuteri on peri-implantitis microflora. BMC Oral Health, 21.","DOI":"10.1186\/s12903-021-01762-2"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1902\/jop.1995.66.5.386","article-title":"Periodontal microbiota of mobile and non-mobile teeth","volume":"66","author":"Grant","year":"1995","journal-title":"J. Periodontol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1034\/j.1600-051x.2000.027012897.x","article-title":"Persistent bacterial colonization of Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans in periodontitis and its association with alveolar bone loss after 6 months of therapy","volume":"27","author":"Chaves","year":"2000","journal-title":"J. Clin. Periodontol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1034\/j.1600-051X.2002.291107.x","article-title":"Porphyromonas gingivalis, Bacteroides forsythus and other putative periodontal pathogens in subjects with and without periodontal destruction","volume":"29","author":"Loos","year":"2002","journal-title":"J. Clin. Periodontol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ghannoum, M.A., Jurevic, R.J., Mukherjee, P.K., Cui, F., Sikaroodi, M., Naqvi, A., and Gillevet, P.M. (2010). Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000713"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Peters, B.A., Wu, J., Hayes, R.B., and Ahn, J. (2017). The oral fungal mycobiome: Characteristics and relation to periodontitis in a pilot study. BMC Microbiol., 17.","DOI":"10.1186\/s12866-017-1064-9"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"a019778","DOI":"10.1101\/cshperspect.a019778","article-title":"The Candida pathogenic species complex","volume":"4","author":"Turner","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1159\/000481833","article-title":"Candida albicans and early childhood caries: A systematic review and meta-analysis","volume":"52","author":"Xiao","year":"2018","journal-title":"Caries Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1177\/0022034518790941","article-title":"Association between oral Candida and bacteriome in children with severe ECC","volume":"97","author":"Xiao","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1177\/0022034514521814","article-title":"Candida and other fungal species: Forgotten players of healthy oral microbiota","volume":"93","author":"Krom","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Vesty, A., Biswas, K., Taylor, M.W., Gear, K., and Douglas, R.G. (2017). Evaluating the impact of DNA extraction method on the representation of human oral bacterial and fungal communities. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169877"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","article-title":"Development of a Classification System for Periodontal Diseases and Conditions","volume":"4","author":"Armitage","year":"1999","journal-title":"Ann. Periodontol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12115","DOI":"10.1073\/pnas.0605127103","article-title":"Microbial diversity in the deep sea and the underexplored \u201crare biosphere\u201d","volume":"103","author":"Sogin","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/bioinformatics\/btt593","article-title":"PEAR: A fast and accurate Illumina Paired-End reAd mergeR","volume":"30","author":"Zhang","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1071\/MA15017","article-title":"DNA barcoding of human and animal pathogenic fungi: The ISHAM-ITS database","volume":"36","author":"Irinyi","year":"2015","journal-title":"Microbiol. Aust."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wilcoxon, F. (1992). Individual comparisons by ranking methods. Breakthroughs in Statistics: Methodology and Distribution, Springer.","DOI":"10.1007\/978-1-4612-4380-9_16"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.tim.2016.12.012","article-title":"Ecology of the oral microbiome: Beyond bacteria","volume":"25","author":"Baker","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"McLean, J.S. (2014). Advancements toward a systems level understanding of the human oral microbiome. Front. Cell. Infect. Microbiol., 4.","DOI":"10.3389\/fcimb.2014.00098"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Janus, M.M., Crielaard, W., Volgenant, C.M.C., Van Der Veen, M.H., Brandt, B.W., and Krom, B.P. (2017). Candida albicans alters the bacterial microbiome of early in vitro oral biofilms. J. Oral Microbiol., 9.","DOI":"10.1080\/20002297.2016.1270613"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/gm467","article-title":"The human mycobiome in health and disease","volume":"5","author":"Cui","year":"2013","journal-title":"Genome Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1002\/eji.201344403","article-title":"Richness and diversity of mammalian fungal communities shape innate and adaptive immunity in health and disease","volume":"44","author":"Rizzetto","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.gpb.2021.05.001","article-title":"Over 50,000 metagenomically assembled draft genomes for the human oral microbiome reveal new taxa","volume":"20","author":"Zhu","year":"2022","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/j.1600-0714.2010.00981.x","article-title":"Candida glabrata and Candida albicans co-infection of an in vitro oral epithelium","volume":"40","author":"Silva","year":"2011","journal-title":"J. Oral Pathol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/21505594.2016.1252015","article-title":"Mining the oral mycobiome: Methods, components, and meaning","volume":"8","author":"Diaz","year":"2017","journal-title":"Virulence"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1177\/0022034520956975","article-title":"Critically appraising the significance of the oral mycobiome","volume":"100","author":"Diaz","year":"2021","journal-title":"J. Dent. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1046\/j.1365-2591.2002.00478.x","article-title":"Prevalence of yeasts in saliva and root canals of teeth associated with apical periodontitis","volume":"35","author":"Egan","year":"2002","journal-title":"Int. Endod. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.jaad.2003.12.034","article-title":"Skin diseases associated with Malassezia species","volume":"51","author":"Gupta","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dupuy, A.K., David, M.S., Li, L., Heider, T.N., Peterson, J.D., Montano, E.A., Dongari-Bagtzoglou, A., Diaz, P.I., and Strausbaugh, L.D. (2014). Redefining the human oral mycobiome with improved practices in amplicon-based taxonomy: Discovery of Malassezia as a prominent commensal. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090899"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1101\/gr.213256.116","article-title":"Identical Bacterial Populations Colonize Premature Infant Gut, Skin, and Oral Microbiomes and Exhibit Different In Situ Growth Rates","volume":"27","author":"Olm","year":"2017","journal-title":"Genome Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.chom.2011.10.006","article-title":"Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement","volume":"10","author":"Hajishengallis","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/jre.12022","article-title":"Association of subgingival colonization of Candida albicans and other yeasts with severity of chronic periodontitis","volume":"48","author":"Canabarro","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1002\/cre2.635","article-title":"Candida species detection in patients with chronic periodontitis: A systematic review and meta-analysis","volume":"8","author":"Slazhneva","year":"2022","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.2041-1014.2012.00663.x","article-title":"Beyond the red complex and into more complexity: The polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology","volume":"27","author":"Hajishengallis","year":"2012","journal-title":"Mol. Oral Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Allison, D.L., Willems, H.M.E., Jayatilake, J.A.M.S., Bruno, V.M., Peters, B.M., and Shirtliff, M.E. (2016). Candida\u2013bacteria interactions: Their impact on human disease. Virulence Mechanisms of Bacterial Pathogens, ASM Press.","DOI":"10.1128\/9781555819286.ch5"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bor, B., Cen, L., Agnello, M., Shi, W., and He, X. (2016). Morphological and physiological changes induced by contact-dependent interaction between Candida albicans and Fusobacterium nucleatum. Sci. Rep., 6.","DOI":"10.1038\/srep27956"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Diaz, P.I., Strausbaugh, L.D., and Dongari-Bagtzoglou, A. (2014). Fungal-bacterial interactions and their relevance to oral health: Linking the clinic and the bench. Front. Cell. Infect. Microbiol., 4.","DOI":"10.3389\/fcimb.2014.00101"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e7870","DOI":"10.7717\/peerj.7870","article-title":"Candida albicans cell wall integrity transcription factors regulate polymicrobial biofilm formation with Streptococcus gordonii","volume":"7","author":"Chinnici","year":"2019","journal-title":"PeerJ"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1093\/infdis\/jiw201","article-title":"Streptococcus oralis and Candida albicans synergistically activate \u03bc-calpain to degrade E-cadherin from oral epithelial junctions","volume":"214","author":"Xu","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.2217\/fmb.14.92","article-title":"Candida albicans and Streptococcus mutans: A potential synergistic alliance to cause virulent tooth decay in children","volume":"9","author":"Koo","year":"2014","journal-title":"Future Microbiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/18\/6418\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:44:06Z","timestamp":1760035446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/18\/6418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":49,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["jcm14186418"],"URL":"https:\/\/doi.org\/10.3390\/jcm14186418","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]}}}