1887

Abstract

Bacteria significantly influence human health and disease, with bacterial biosynthetic gene clusters (BGCs) being crucial in the microbiome–host and microbe–microbe interactions.

Despite extensive research into BGCs within the human gut microbiome, their roles in the oral microbiome are less understood.

This pilot study utilizes high-throughput shotgun metagenomic sequencing to examine the oral microbiota in different niches, particularly focusing on the association of BGCs with periodontitis.

We analysed saliva, subgingival plaque and supragingival plaque samples from periodontitis patients (=23) and controls (=16). DNA was extracted from these samples using standardized protocols. The high-throughput shotgun metagenomic sequencing was then performed to obtain comprehensive genetic information from the microbial communities present in the samples.

Our study identified 10 742 BGCs, with certain clusters being niche-specific. Notably, aryl polyenes and bacteriocins were the most prevalent BGCs identified. We discovered several ‘novel’ BGCs that are widely represented across various bacterial phyla and identified BGCs that had different distributions between periodontitis and control subjects. Our systematic approach unveiled the previously unexplored biosynthetic pathways that may be key players in periodontitis.

Our research expands the current metagenomic knowledge of the oral microbiota in both healthy and periodontally diseased states. These findings highlight the presence of novel biosynthetic pathways in the oral cavity and suggest a complex network of host–microbe and microbe–microbe interactions, potentially influencing periodontal disease. The BGCs identified in this study pave the way for future investigations into the role of small-molecule-mediated interactions within the human oral microbiota and their impact on periodontitis.

Funding
This study was supported by the:
  • General Research Fund (GRF) (Award 17121820)
    • Principle Award Recipient: RoryM. Watt
  • Seed funding for new staff
    • Principle Award Recipient: MohamadKoohi-Moghadam
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-10-08
2024-11-05
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References

  1. Sedghi L, DiMassa V, Harrington A, Lynch SV, Kapila YL. The oral microbiome: role of key organisms and complex networks in oral health and disease. Periodontol 2000 2021; 87:107–131 [View Article] [PubMed]
    [Google Scholar]
  2. Mark Welch JL, Rossetti BJ, Rieken CW, Dewhirst FE, Borisy GG. Biogeography of a human oral microbiome at the micron scale. Proc Natl Acad Sci U S A 2016; 113:E791–800 [View Article] [PubMed]
    [Google Scholar]
  3. Mark Welch JL, Dewhirst FE, Borisy GG. Biogeography of the oral microbiome: the site-specialist hypothesis. Annu Rev Microbiol 2019; 73:335–358 [View Article] [PubMed]
    [Google Scholar]
  4. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet 2012; 13:260–270 [View Article] [PubMed]
    [Google Scholar]
  5. Rutledge PJ, Challis GL. Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nat Rev Microbiol 2015; 13:509–523 [View Article] [PubMed]
    [Google Scholar]
  6. Netzker T, Fischer J, Weber J, Mattern DJ, König CC et al. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front Microbiol 2015; 6:299 [View Article] [PubMed]
    [Google Scholar]
  7. Aleti G, Baker JL, Tang X, Alvarez R, Dinis M et al. Identification of the bacterial biosynthetic gene clusters of the oral microbiome illuminates the unexplored social language of bacteria during health and disease. mBio 2019; 10:e00321-19 [View Article] [PubMed]
    [Google Scholar]
  8. Liu L, Hao T, Xie Z, Horsman GP, Chen Y. Genome mining unveils widespread natural product biosynthetic capacity in human oral microbe Streptococcus mutans. Sci Rep 2016; 6:37479 [View Article] [PubMed]
    [Google Scholar]
  9. Alzahrani MM, Bamashmous S, Alkharobi H, Alghamdi A, Alharbi RH et al. Mouth rinses efficacy on salivary SARS-CoV-2 viral load: a randomized clinical trial. J Med Virol 2023; 95:e28412 [View Article] [PubMed]
    [Google Scholar]
  10. Lim FY, Goo CL, Leung WK, Goh V. Validation of the malay oral impacts on daily performances and evaluation of oral health-related quality of life in a multi-ethnic urban Malaysian population: a cross-sectional study. Int J Environ Res Public Health 2022; 19:16944 [View Article] [PubMed]
    [Google Scholar]
  11. Petersen PE, Baez RJ. WHO Assessment of Oral Health Status, 5th Geneva: World Health Organization; 2013 pp 35–56
    [Google Scholar]
  12. Iranzo-Cortés JE, Montiel-Company JM, Almerich-Silla JM. Caries diagnosis: agreement between WHO and ICDAS II criteria in epidemiological surveys. Community Dent Health 2013; 30:108–111 [PubMed]
    [Google Scholar]
  13. Ekstrand KR, Gimenez T, Ferreira FR, Mendes FM, Braga MM. The International caries detection and assessment system - ICDAS: a systematic review. Caries Res 2018; 52:406–419 [View Article] [PubMed]
    [Google Scholar]
  14. Chiu J, Zheng Y, Lai S, Chan WS, Yeung S et al. Periodontal conditions of essential hypertension attendees to a general hospital in Hong Kong. Aust Dent J 2020; 65:259–268 [View Article] [PubMed]
    [Google Scholar]
  15. Dawes C. Circadian rhythms in human salivary flow rate and composition. J Physiol 1972; 220:529–545 [View Article] [PubMed]
    [Google Scholar]
  16. Li D, Liu C-M, Luo R, Sadakane K, Lam T-W. MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics 2015; 31:1674–1676 [View Article] [PubMed]
    [Google Scholar]
  17. Blin K, Shaw S, Kloosterman AM, Charlop-Powers Z, van Wezel GP et al. antiSMASH 6.0: improving cluster detection and comparison capabilities. Nucleic Acids Res 2021; 49:W29–W35 [View Article] [PubMed]
    [Google Scholar]
  18. Youens-Clark K. Mastering Python for Bioinformatics O’Reilly Media, Inc; 2021
    [Google Scholar]
  19. von Meijenfeldt FAB, Arkhipova K, Cambuy DD, Coutinho FH, Dutilh BE. Robust taxonomic classification of uncharted microbial sequences and bins with CAT and BAT. Genome Biol 2019; 20:217 [View Article] [PubMed]
    [Google Scholar]
  20. Parks DH, Chuvochina M, Rinke C, Mussig AJ, Chaumeil P-A et al. GTDB: an ongoing census of bacterial and archaeal diversity through a phylogenetically consistent, rank normalized and complete genome-based taxonomy. Nucleic Acids Res 2022; 50:D785–D794 [View Article] [PubMed]
    [Google Scholar]
  21. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods 2012; 9:357–359 [View Article] [PubMed]
    [Google Scholar]
  22. Kautsar SA, van der Hooft JJJ, de Ridder D, Medema MH. BiG-SLiCE: a highly scalable tool maps the diversity of 1.2 million biosynthetic gene clusters. Gigascience 2021; 10:giaa154 [View Article] [PubMed]
    [Google Scholar]
  23. Randle-Boggis RJ, Helgason T, Sapp M, Ashton PD. Evaluating techniques for metagenome annotation using simulated sequence data. FEMS Microbiol Ecol 2016; 92:fiw095 [View Article] [PubMed]
    [Google Scholar]
  24. Chen Q, Wan Y, Lei Y, Zobel J, Verspoor K. Evaluation of CD-HIT for constructing non-redundant databases. In In 2016 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) IEEE; 2016 pp 703–706
    [Google Scholar]
  25. Navarro-Muñoz JC, Selem-Mojica N, Mullowney MW, Kautsar SA, Tryon JH et al. A computational framework to explore large-scale biosynthetic diversity. Nat Chem Biol 2020; 16:60–68 [View Article] [PubMed]
    [Google Scholar]
  26. Kautsar SA, Blin K, Shaw S, Navarro-Muñoz JC, Terlouw BR et al. MIBiG 2.0: a repository for biosynthetic gene clusters of known function. Nucleic Acids Res 2020; 48:D454–D458 [View Article] [PubMed]
    [Google Scholar]
  27. Smoot ME, Ono K, Ruscheinski J, Wang P-L, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 2011; 27:431–432 [View Article] [PubMed]
    [Google Scholar]
  28. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol 2018; 89 Suppl 1:S159–S172 [View Article] [PubMed]
    [Google Scholar]
  29. McMahon RJ. Biotin in metabolism and molecular biology. Annu Rev Nutr 2002; 22:221–239 [View Article] [PubMed]
    [Google Scholar]
  30. de Oliveira Filho JWG, Islam MT, Ali ES, Uddin SJ, Santos JV de O et al. A comprehensive review on biological properties of citrinin. Food Chem Toxicol 2017; 110:130–141 [View Article] [PubMed]
    [Google Scholar]
  31. Hudson GA. Bioinformatic mapping of radical SAM-dependent ripps identifies new Cα, Cβ, and Cγ-linked thioether-containing peptides. J Am Chem Soc 2019; 141:8228
    [Google Scholar]
  32. Yu Y, Zhang Q, van der Donk WA. Insights into the evolution of lanthipeptide biosynthesis. Protein Sci 2013; 22:1478–1489 [View Article] [PubMed]
    [Google Scholar]
  33. Stubbendieck RM, Zelasko SE, Safdar N, Currie CR. Biogeography of bacterial communities and specialized metabolism in human aerodigestive tract microbiomes. Microbiol Spectr 2021; 9:e0166921 [View Article] [PubMed]
    [Google Scholar]
  34. Johnston I, Osborn LJ, Markley RL, McManus EA, Kadam A et al. Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation. NPJ Biofilms Microbiomes 2021; 7:56 [View Article] [PubMed]
    [Google Scholar]
  35. Simons A, Alhanout K, Duval RE. Bacteriocins, antimicrobial peptides from bacterial origin: overview of their biology and their impact against multidrug-resistant bacteria. Microorganisms 2020; 8:639 [View Article] [PubMed]
    [Google Scholar]
  36. Cotter PD, Ross RP, Hill C. Bacteriocins - a viable alternative to antibiotics?. Nat Rev Microbiol 2013; 11:95–105 [View Article] [PubMed]
    [Google Scholar]
  37. Santagati M, Scillato M, Patanè F, Aiello C, Stefani S. Bacteriocin-producing oral streptococci and inhibition of respiratory pathogens. FEMS Immunol Med Microbiol 2012; 65:23–31 [View Article]
    [Google Scholar]
  38. Conrads G, Westenberger J, Lürkens M, Abdelbary MMH. Isolation and bacteriocin-related typing of Streptococcus dentisani. Front Cell Infect Microbiol 2019; 9:110 [View Article] [PubMed]
    [Google Scholar]
  39. de Souza de Azevedo PO, Mendonça CMN, Moreno ACR, Bueno AVI, de Almeida SRY et al. Antibacterial and antifungal activity of crude and freeze-dried bacteriocin-like inhibitory substance produced by Pediococcus pentosaceus. Sci Rep 2020; 10:12291 [View Article] [PubMed]
    [Google Scholar]
  40. Cannon RD. Oral fungal infections: past, present, and future. Front Oral Health 2022; 3:838639 [View Article] [PubMed]
    [Google Scholar]
  41. How KY, Song KP, Chan KG. Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front Microbiol 2016; 7:53 [View Article] [PubMed]
    [Google Scholar]
  42. Yang L-H, Cheng H-Y, Zhu T-T, Wang H-C, Haider MR et al. Resorcinol as a highly efficient aromatic electron donor in bioelectrochemical system. J Hazard Mater 2021; 408:124416 [View Article] [PubMed]
    [Google Scholar]
  43. Bleich R, Watrous JD, Dorrestein PC, Bowers AA, Shank EA. Thiopeptide antibiotics stimulate biofilm formation in Bacillus subtilis. Proc Natl Acad Sci U S A 2015; 112:3086–3091 [View Article] [PubMed]
    [Google Scholar]
  44. Rigauts C, Aizawa J, Taylor SL, Rogers GB, Govaerts M et al. R othia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease. Eur Respir J 2022; 59:5 [View Article] [PubMed]
    [Google Scholar]
  45. Kaci G, Goudercourt D, Dennin V, Pot B, Doré J et al. Anti-inflammatory properties of Streptococcus salivarius, a commensal bacterium of the oral cavity and digestive tract. Appl Environ Microbiol 2014; 80:928–934 [View Article] [PubMed]
    [Google Scholar]
  46. Diao J, Yuan C, Tong P, Ma Z, Sun X et al. Potential roles of the free salivary microbiome dysbiosis in periodontal diseases. Front Cell Infect Microbiol 2021; 11:711282 [View Article] [PubMed]
    [Google Scholar]
  47. Choi SY, Cho IJ, Lee Y, Kim YJ, Kim KJ et al. Microbial polyhydroxyalkanoates and nonnatural polyesters. Adv Mater 2020; 32:e1907138 [View Article] [PubMed]
    [Google Scholar]
  48. Mathur H, Field D, Rea MC, Cotter PD, Hill C et al. Fighting biofilms with lantibiotics and other groups of bacteriocins. NPJ Biofilms Microbiomes 2018; 4:9 [View Article] [PubMed]
    [Google Scholar]
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