Background The disruption of microbiota balance could be a pivotal factor in the complications arising from periodontal disease-induced inflammation outside the mouth. Nonetheless, it remains uncertain whether there is a direct causal relationship between the oral and gut microbiomes and gingivitis, especially in distinguishing between acute and chronic gingivitis. Methods We performed a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics from FinnGen data (149 acute gingivitis cases, 850 chronic gingivitis cases, and 195,395 controls) to explore the causal role of oral and gut microbiota. The primary analysis employed the inverse-variance weighted (IVW) method, augmented by four supplementary approaches: weighted median, weighted mode, and MR Egger regression, all aimed at detecting and adjusting for horizontal pleiotropy. Results In the gut microbiota, the results of IVW showed that class Negativicutes, Verrucomicrobiae, genus Butyricicoccus, Eubacterium, Lactobacillus, order Selenomonadales and Verrucomicrobiales were linked to a higher risk of acute gingivitis, while family Peptostreptococcaceae, genus Coprococcus2, and genus Lachnospiraceae UCG001 were linked to a lower risk of acute gingivitis (P < 0.05). Class Erysipelotrichia, Methanobacteria, Verrucomicrobiae, family Defluviitaleaceae, Erysipelotrichaceae, Methanobacteriaceae, Verrucomicrobiaceae, genus Akkermansia, Christensenellaceae R 7group, Defluviitaleaceae UCG011, Methanobrevibacter, genus Paraprevotella, Senegalimassilia, order Erysipelotrichales, Methanobacteriales, Verrucomicrobiales, and phylum Cyanobacteria were linked to a higher risk of chronic gingivitis, while family Clostridiales vadin BB60 group, genus Allisonella, Dorea, and Lachnospiraceae UCG004 were linked to a lower risk of chronic gingivitis (P < 0.05). And in the oral microbiota, unknown Porphyromonas species (ASV0008) and Genus Porphyromonas were linked to higher risk of acute gingivitis (P < 0.05). Unknown Neisseria species (ASV0004) and unknown Veillonella species (ASV0001) were linked to higher risk of chronic gingivitis, while Class Bacilli was linked to lower risk of chronic gingivitis (P < 0.05). Conclusions This MR analysis confirms the distinct causal relationships between microbiota and both acute and chronic gingivitis, providing insights into potential prevention strategies in European. Clinical trial number Not applicable.

Oral and gut microbiota in gingivitis subtypes: a causal inference study using Mendelian randomization

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2025年7月28日

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Jichao Lin,
Qingjiang Xu,
Wei Bi,
Youcheng Yu,
Qinglian Wang

摘要

Background

The disruption of microbiota balance could be a pivotal factor in the complications arising from periodontal disease-induced inflammation outside the mouth. Nonetheless, it remains uncertain whether there is a direct causal relationship between the oral and gut microbiomes and gingivitis, especially in distinguishing between acute and chronic gingivitis.

Methods

We performed a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics from FinnGen data (149 acute gingivitis cases, 850 chronic gingivitis cases, and 195,395 controls) to explore the causal role of oral and gut microbiota. The primary analysis employed the inverse-variance weighted (IVW) method, augmented by four supplementary approaches: weighted median, weighted mode, and MR Egger regression, all aimed at detecting and adjusting for horizontal pleiotropy.

Results

In the gut microbiota, the results of IVW showed that class Negativicutes, Verrucomicrobiae, genus Butyricicoccus, Eubacterium, Lactobacillus, order Selenomonadales and Verrucomicrobiales were linked to a higher risk of acute gingivitis, while family Peptostreptococcaceae, genus Coprococcus2, and genus Lachnospiraceae UCG001 were linked to a lower risk of acute gingivitis (P < 0.05). Class Erysipelotrichia, Methanobacteria, Verrucomicrobiae, family Defluviitaleaceae, Erysipelotrichaceae, Methanobacteriaceae, Verrucomicrobiaceae, genus Akkermansia, Christensenellaceae R 7group, Defluviitaleaceae UCG011, Methanobrevibacter, genus Paraprevotella, Senegalimassilia, order Erysipelotrichales, Methanobacteriales, Verrucomicrobiales, and phylum Cyanobacteria were linked to a higher risk of chronic gingivitis, while family Clostridiales vadin BB60 group, genus Allisonella, Dorea, and Lachnospiraceae UCG004 were linked to a lower risk of chronic gingivitis (P < 0.05). And in the oral microbiota, unknown Porphyromonas species (ASV0008) and Genus Porphyromonas were linked to higher risk of acute gingivitis (P < 0.05). Unknown Neisseria species (ASV0004) and unknown Veillonella species (ASV0001) were linked to higher risk of chronic gingivitis, while Class Bacilli was linked to lower risk of chronic gingivitis (P < 0.05).

Conclusions

This MR analysis confirms the distinct causal relationships between microbiota and both acute and chronic gingivitis, providing insights into potential prevention strategies in European.

Clinical trial number

Not applicable.