未培養および培養可能な歯周病関連細菌は、妊娠中の歯周病炎症や早産低体重児出産と関連している

Unculturable and culturable periodontal-related bacteria are associated with periodontal inflammation during pregnancy and with preterm low birth weight delivery.

抄録

最近の研究では、培養可能な歯周病原菌が早産低体重児（PLBW）と関連していることが明らかになりました。しかし、口腔内のマイクロバイオームには、何百もの「培養が困難な」あるいは「まだ培養できない」細菌種が存在しています。早産低体重児（PLBW）の出産における培養不能および培養可能な歯周炎関連細菌の潜在的な役割を探るため、今回の前向き研究では90名の妊婦を募集しました。ポケットのプロービング深さ，プロービング時の出血，臨床的付着レベルなどの歯周病パラメータを，第2期に記録し，口腔衛生と生活習慣に関するインタビューを行った。また、唾液と血清も採取しました。出産後には、出産結果が記録された。唾液中の歯周炎関連の非培養菌（Eubacterium saphenum, Fretibacterium sp. human oral taxon(HOT) 360, TM7 sp. HOT 356, Rothia dentocariosa）と培養菌（Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Prevotella intermedia）の量を定量化するためにリアルタイムPCR分析を行った。さらに，ELISA法により，血清中の歯周病菌に対するIgG抗体価を測定した。被験者は、歯周病の状態に応じて、健康群（H, n=20）と歯周炎・歯肉炎群（PG, n=70）に分類した。PG群では、H群に比べてブラッシング時間が有意に短かった。90 名の被験者のうち 22 名が PLBW 乳児を出産した。PLBW群と健康な出産（HD）群の間で，歯周病パラメータと歯周病病原菌に対する血清IgG値に有意な差はなかった。しかし，順序ロジスティック回帰分析の結果，Treponema denticola，Prevotella intermedia，Fretibacterium sp.HOT360の量が多く，Rothia dentocariosaの量が少ないことが，妊娠中の歯周病の有無と有意に関連していた．さらに、唾液中のEubacterium saphenumの量と血清中のAggregatibacter actinomycetemcomitansに対するIgGは、PLBWと負の相関関係にあった。以上のことから、培養不可能な歯周病関連細菌は、妊娠中の歯周病炎症の存在とその後のPLBWの両方に重要な役割を果たしている可能性がある。

Recent studies revealed culturable periodontal keystone pathogens are associated with preterm low birth weight (PLBW). However, the oral microbiome is also comprised of hundreds of 'culture-difficult' or 'not-yet-culturable' bacterial species. To explore the potential role of unculturable and culturable periodontitis-related bacteria in preterm low birth weight (PLBW) delivery, we recruited 90 pregnant women in this prospective study. Periodontal parameters, including pocket probing depth, bleeding on probing, and clinical attachment level were recorded during the second trimester and following interviews on oral hygiene and lifestyle habits. Saliva and serum samples were also collected. After delivery, birth results were recorded. Real-time PCR analyses were performed to quantify the levels of periodontitis-related unculturable bacteria (Eubacterium saphenum, Fretibacterium sp. human oral taxon(HOT) 360, TM7 sp. HOT 356, and Rothia dentocariosa), and cultivable bacteria (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum and Prevotella intermedia) in saliva samples. In addition, ELISA analyses were used to determine the IgG titres against periodontal pathogens in serum samples. Subjects were categorized into a Healthy group (H, n = 20) and periodontitis/gingivitis group (PG, n = 70) according to their periodontal status. The brushing duration was significantly lower in the PG group compared to the H group. Twenty-two of 90 subjects delivered PLBW infants. There was no significant difference in periodontal parameters and serum IgG levels for periodontal pathogens between PLBW and healthy delivery (HD) groups. However, ordinal logistic regression analysis revealed that a higher abundance of Treponema denticola, Prevotella intermedia, Fretibacterium sp. HOT360 and lower levels of Rothia dentocariosa were significantly associated with the presence of periodontal disease during pregnancy. Moreover, the amount of Eubacterium saphenum in saliva and serum IgG against Aggregatibacter actinomycetemcomitans were negatively correlated with PLBW. Taken together, unculturable periodontitis-associated bacteria may play an important role both in the presence of periodontal inflammation during pregnancy and subsequent PLBW.