Host Genotype Links to Salivary and Gut Microbiota by Periodontal Status

Kurushima, Yuko; Wells, Philippa M; Bowyer, Ruth C E; Zoheir, Noha; Doran, Stephen; Richardson, Josie; Sprockett, Daniel D.; Relman, David A.; Steves, Claire J.; Nibali, Luigi

doi:10.1177/00220345221125402

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…Exploring from the standpoint of host genetic variation becomes an attractive and crucial research field [ 39 ]. A recent study in the TwinsUK registry, for example, confirmed the connections between a collection of putative host genetic variants and gut microbial composition by periodontal condition [ 40 ]. Similar benefits applied to the research of MR, the development of MR provides a new paradigm for studying causal linkages, which has been widely applied in the field of periodontitis (Additional file 1 : Table S7).…”

Section: Discussionmentioning

confidence: 97%

Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study

Ye,

Liu,

Bai

et al. 2023

J Transl Med

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Background Recent research has established the correlation between gut microbiota and periodontitis via oral-gut axis. Intestinal dysbiosis may play a pivotal bridging role in extra-oral inflammatory comorbidities caused by periodontitis. However, it is unclear whether the link is merely correlative or orchestrated by causative mechanistic interactions. This two-sample Mendelian randomization (MR) study was performed to evaluate the potential bidirectional causal relationships between gut microbiota and periodontitis. Materials and Methods A two-sample MR analysis was performed using summary statistics from genome-wide association studies (GWAS) for gut microbiota (n = 18,340) and periodontitis (cases = 12,251; controls = 22,845). The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. The PhenoScanner database was then searched for pleiotropy SNPs associated with potential confounders. In order to identify the possibly influential SNPs, we further conducted the leave-one-out analysis. Finally, a reverse MR analysis was performed to evaluate the possibility of links between periodontitis and genetically predicted gut microbiota alternation. Results 2,699 single nucleotide polymorphisms (SNPs) associated with 196 microbiota genera were selected as instrumental variables (IVs). IVW method suggested that order Enterobacteriales (OR: 1.35, 95% CI 1.10–1.66), family Bacteroidales S24.7group (OR: 1.22, 95% CI 1.05–1.41), genus Lachnospiraceae UCG008 (OR: 1.16, 95% CI 1.03–1.31), genus Prevotella 7 (OR: 1.11, 95% CI 1.01–1.23), and order Pasteurellales (OR: 1.12, 95% CI 1.00–1.26) may be associated with a higher risk of periodontitis, while genus Ruminiclostridium 6 may be linked to a lower risk (OR: 0.82, 95% CI 0.70–0.95). The sensitivity and heterogeneity analyses yielded no indication of horizontal pleiotropy or heterogeneity. Only the association between order Enterobacteriales and the likelihood of periodontitis remained consistent across all alternative MR approaches. In the reverse MR analysis, four microbiota genera were genetically predicted to be down-regulated in periodontitis, whereas two were predicted to be up-regulated. Conclusions The present MR analysis demonstrated the potential bidirectional causal relationships between gut microbiota and periodontitis. Our research provided fresh insights for the prevention and management of periodontitis. Future research is required to support the finding of our current study.

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Section: Discussionmentioning

confidence: 97%

Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study

Ye,

Liu,

Bai

et al. 2023

J Transl Med

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Association between polymorphisms of anti-inflammatory gene alleles and periodontitis risk in a Chinese Han population

Li,

Zhang,

Zhang

et al. 2023

Clin Oral Invest

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Associations between Host Genetic Variants and Subgingival Microbiota in Patients with the Metabolic Syndrome

Nibali,

Stephen,

Allaker

et al. 2023

IJMS

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Host genetic variants may affect oral biofilms, playing a role in the periodontitis–systemic disease axis. This is the first study to assess the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed, assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis testing) and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed and stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics with no genome-wide associations detected for periodontitis severity or Mets components at p < 10−7. Severe periodontitis was associated with pathogenic genera and species. Some SNPs correlated with specific bacterial genera as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and the microbiome.

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Host Genotype Links to Salivary and Gut Microbiota by Periodontal Status

Cited by 3 publications

References 41 publications

Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study

Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study

Association between polymorphisms of anti-inflammatory gene alleles and periodontitis risk in a Chinese Han population

Associations between Host Genetic Variants and Subgingival Microbiota in Patients with the Metabolic Syndrome

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