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- Eriksson, Linda, 1979-
(författare)
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Oral microbiota in relation to host traits, environment, and dental caries
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Dental caries still appears at high prevalence worldwide. Disease distribution is skewed with more disease in socio-economically weak groups. However, also in populations considered as “low caries” there is a significant fraction with continuous disease development. Caries develops when the hard tissues of the tooth is demineralized, which occurs when pH drops below approximately 5.5 for enamel and 6.2 for dentine. The pH drop follows fermentation and acid production by tooth colonising bacteria upon dietary carbohydrate exposure. Thus, understanding the interactions between oral bacteria, diet and host factors is essential for managing the disease. The overall aim of this thesis was to study the oral microbiota in relation to caries and its association with sugar intake and driving forces behind sugar intake.Material and method: Saliva and tooth biofilm samples, information on caries status, dietary habits and other lifestyle data were collected from 17-23 year old participants. The participants also carried out a tasting session for the tastes sour, sweet and bitter. Genomic DNA was extracted from saliva and tooth biofilm and analysed using 16S rDNA amplicon sequencing with two platforms. Taxa were classified against the eHOMD database. Taste gene genotyping was done by mass spectrometry. Data were compared by univariate and multivariate statistical methods.Results: Oral microbiota was analysed in 64 adolescents. Streptococcus mutans, Scardovia wiggsiae, Bifidobacterium longum and Lepotrichia sp. HOT 498 displayed strong association with having caries, whereas Corynebacterium matruchotii and tooth brushing were associated with being caries-free. It was also confirmed that S.mutans was not compulsory for having caries. The oral microbiota in caries affected adolescents without S. mutans in was evaluated, and found to be characterised by a wide panel of saccharolytic non-S.mutans species. In contrast, tooth biofilms in individuals with caries and S. mutans were enriched for relatively few saccharolytic species in addition to S.mutans. Further, the overall microbiota pattern fell into four distinct clusters with deviating caries prevalence. The association with a set of lifestyle factors was searched, and sugar intake was found to differ between the groups. In the cluster with the highest sugar intake, the microbiota was less diverse and low sugar intake was characterized by enumeration of C. durum, C. matruchotiiand S. sanguinis. To deepen the knowledge on mechanisms behind sweet food intake, single nucleotide polymorphisms (SNP) genotyping in genes reported to be associated with taste regulation or sugar intake was done. SNPs in four genes were associated with sensitivity and preference for sweet taste and in the SLC2A2 gene also with caries.Conclusions: This project confirmed that dental caries is not a single species disease, and in the present population S. mutans, S. wiggsiae, and B. longum were significant for having caries. It was also confirmed that S. mutans is not essential for having caries. Tooth biofilm microbiota in S. mutans free adolescents was characterised by a larger diversity of species than seen in those with caries and S. mutans. It may be hypothesised that sugar intake and associated pH drops alone or in interaction with host biology play a role in the differentiation of the microbiota into the distinct profiles. This was supported by the finding that sugar intake was related to microbiota clustering and less community diversity. In this perspective the genetically based influence on sugar preference should be taken into account in dietary counselling which is an important aspect in caries prevention and treatment.
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| 2. |
- Sheng, Nongfei, 1988-
(författare)
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Revisiting dental caries as an immunodeficiency disorder
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Worldwide, dental caries is the major human chronic disease, with billions of people affected in terms of life quality impairment and high society costs that consumes 5-10% of the global healthcare budget. In Western countries dental caries has declined dramatically, with a trajectory of 15% high-risk individuals with recurrent caries and a non-responder behavior to standard prevention. This dissertation work focuses on revisiting the primary causes of caries development by exploring human and Streptococcus mutans genetic variation in a prospective case-control sample of 452 Swedish adolescents followed from 12 and 17 years of age.Genetic variation of PRH1 and PRH2, encoding acidic proline-rich protein receptors for indigenous oral streptococci and actinomycetes, specified high (P4a), moderate (P6) and low (P1) caries phenotypes of different risk and causal profiles (Paper I). Susceptible individuals thus classified into the immunodeficiency caries type (P4a) or the lifestyle caries type (P1) that accounted for naturally resistant individuals. Orthodontic treatment during adolescence exerted a further negative load that resulted in an even bigger difference in caries progression between P4a and P1 individuals. Importantly, immunodeficiency P4a individuals were identified as risk individuals at the clinic and therefore given extra fluoride.Adhesin gene variation in S. mutans specified SpaP A/B/C and Cnm/Cbm adhesion types that matched individual caries progression (Paper II). The saliva/DMBT1 binding avidity of high cariogenicity SpaP and Cnm but not of low cariogenicity SpaP A types correlated positively with the caries activity of the individual strain donor. SpaP-guided MLST typing also revealed SpaP A/B/C biotypes with high SpaP B and low SpaP A cariogenicity lineages that besides adhesion differed in acid production and acid tolerance properties. The SpaP A/B/C receptor-binding V-regions had markedly different structures. In paper III, we found unstable residency of a mixed and fluctuating SpaP A/B/C adhesion mode, a high cariogenicity SpaP B-1 subtype and Cnm adhesin expression and glycosylation to contribute to mono-microbial caries progression in naturally resistant low caries P1 phenotypes. By, contrast, moderate- and high-caries P6 and P4a phenotypes contributed to poly- and meta-microbial caries progression. In addition, the S. mutans adhesion types showed specificity (tropism) for individual hosts and plausible family distribution patterns.DMBT1 protein size isoforms I-III predicted caries progression but differently in the PRH1/PRH2 genetic background and influenced the infection profile of S. mutans adhesion and virulence types (Paper IV). Caries progression increased as DMBT1 isoform size decreased in the order of isoform I > II > III, suggesting that loss of the large isoform III glycotype may impair immunity. The finding that DMBT1 isoform variation did not add predictive power to the P4a+ but to P4a- phenotypes allowed a novel sick and health classification system.In conclusion, PRH1, PRH2 may represent a pattern recognition and immunity pathway for tooth homeostasis and formation of the indigenous flora on teeth. It can predict prospective caries risk and might be implemented in caries prevention based on genetic risk and cause at the clinical level. DMBT1 appears as an evolutionary different but intertwined immunity pathway for surveillance of infectious agents in general at teeth and mucosal surfaces. The S. mutans organism is heterogenous with biotypes and lineages that match individual caries development. Narrowing both S. mutans and PRH1, PRH2 phenotypes suggest a mono- (P1), poly- (P6) and even meta- (P4a) microbial characters of dental caries.
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