Contents lists available at ScienceDirect Human Microbiome Journal journal homepage: www.elsevier.com/locate/humic Adjunctive dental therapies in caries-active children: Shifting the cariogenic salivary microbiome from dysbiosis towards non-cariogenic health Claudia Lyashenko a,1 , Elisa Herrman b,1 , Jessica Irwin c,1 , Allie James c,1 , Shay Strauss a,1 , John Warner c,1 , Brandon Khor b , Michael Snow b , Stephanie Ortiz b , Erin Waid b , Bishoy Nasry b , Jennifer Chai b , Carissa Choong b , Elizabeth Palmer c , Kim Kutsch d , Anna Forsyth c , Dongseok Choi e,f , Tom Maier a , Curtis A. Machida a,c, ⁎ a Department of Integrative Biomedical and Diagnostic Sciences, Oregon Health & Science University School of Dentistry, United States b Academic DMD Program, Oregon Health & Science University School of Dentistry, United States c Department of Pediatric Dentistry, Oregon Health & Science University School of Dentistry, United States d Oregon Health & Science University School of Dentistry, United States e OHSU-PSU School of Public Health, United States f Graduate School of Dentistry, Kyunghee University, South Korea ARTICLE INFO Keywords: Salivary microbiome Dental caries Caries-active children Microbiome shift Stentrophomonas maltophila Povidone iodine Dysbiosis Oral health ABSTRACT Background: The oral microbiome is a complex assembly of microbial species, whose constituents can tilt the balance towards progression of oral disease or sustained health. Recently we identified sex-specific differences in the salivary microbiome contained within caries-active and caries-free children. In this study, we sought to ascertain if adjunctive dental therapies, including povidone iodine and chlorhexidine, were effective in shifting the cariogenic microbiome from dysbiosis to non-cariogenic health. Design: We recruited young children (ages 2–12 years) to enter five enrollment groups, with each group (N = 9–30 participants/group) receiving caries restorative and/or adjunctive therapies, either singularly or in combination (OHSU IRB #6535). Saliva specimens were collected pre- and post-treatment (4–8 weeks) of caries preventive measures, and oral microbiota were identified using next generation sequencing (HOMINGS, Forsyth Institute, Cambridge, MA). Results: With the use of multi-dimensional scaling plots, support vector machine learning, odds ratio analysis, and other statistical methods, we have determined that treatment with povidone iodine can shift the composition of the salivary cariogenic microbiome to include higher proportions of aerobic microorganisms, such as Stentrophomonas maltophila, as well as non-cariogenic, anaerobic microorganisms including Poryphyromonas and Fusobacterium species. Conclusion: We have identified microorganisms that are associated with caries-active children and have de- termined that povidone iodine is an effective adjunctive therapy that has the potential to shift the composition of the cariogenic microbiome to one more closely aligned with non-cariogenic health. 1. Introduction The oral microbiome is a complex collection of microbial species, the balance of which contributes to the development of oral disease processes and health. Of the various microbial communities in humans, the oral microbiome is considered as one of the most constant over time [1–3]. Following administration of antibiotics, the oral microbiome exhibits greater resilience and eventual full recovery, whereas the gut microbiota tends to sustain long-term modifications [4]. Though the oral microbiome exhibits natural defenses to drastic shifts in microbial composition via the effects of saliva and other factors, it exhibits limited capability in recovering from disease states that result from the over- abundance of specific oral pathogens. Dental caries is a common oral disease affecting children and adults, https://doi.org/10.1016/j.humic.2020.100077 ⁎ Corresponding author at: Department of Integrative Biomedical and Diagnostic Sciences, Oregon Health & Science University School of Dentistry, 2730 SW Moody Avenue, Portland, OR 97201, United States. E-mail address: machidac@ohsu.edu (C.A. Machida). 1 Primary contributors to this work. Human Microbiome Journal 18 (2020) 100077 Available online 31 August 2020 2452-2317/ © 2020 Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). T