Vogtmann Emily, Yano Yukiko, Shi Jianxin, Wan Yunhu, Purandare Vaishnavi, McLean Jody, Li Shilan, Knight Rob, Kahle Lisa, Hullings Autumn G, Hua Xing, Graubard Barry I, Gillison Maura L, Caporaso J Gregory, Bokulich Nicholas A, Blaser Martin J, Freedman Neal D, Chaturvedi Anil K, Abnet Christian C
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Frederick National Laboratory for Cancer Research/Leidos Biomedical Research Laboratory, Inc, Frederick, MD, USA.
medRxiv. 2024 Dec 5:2024.12.03.24318413. doi: 10.1101/2024.12.03.24318413.
Poor oral health, including periodontal disease, is associated with oral microbiome changes and increased mortality risk. However, no large studies have evaluated whether the oral microbiome is directly associated with mortality.
To evaluate whether measures of the oral microbiome is prospectively associated with all-cause mortality.
A cross-sectional survey with samples collected from 2009-2012 and mortality linkage to the restricted-use National Death Index (NDI) through 2019.
The National Health and Nutrition Examination Survey (NHANES) 2009-2012, a multistage probability sample of the US population.
NHANES participants 20- to 69-years-old who were eligible for linkage to the NDI and provided oral rinse specimens (N=7,721, representing approximately 194 million individuals).
Oral microbiome ascertained by sequencing the V4 region of the 16S rRNA gene of extracted DNA from oral rinse specimens. Alpha diversity, beta diversity, and genus-level data were generated using DADA2 and QIIME.
All-cause mortality.
After an average of 8.8 years, a total of 426 participants died. Using Cox proportional hazards regression and after controlling for multiple comparisons where appropriate, continuous alpha diversity was inversely associated with all-cause mortality, but only the association for the Shannon-Weiner index was significant with full adjustment for major risk factors (hazard ratio [HR] per standard deviation [SD]=0.85; 95% confidence interval [CI]=0.74-0.98). The principal coordinate analysis (PCoA) vector 2 from the Bray-Curtis dissimilarity matrix (HR per SD=0.83; 95% CI=0.73-0.93) and PCoA1 from weighted UniFrac (HR per SD=0.86; 95% CI=0.75-0.98) were significantly associated with all-cause mortality after full adjustment. Few associations were observed at the genus-level after Bonferroni correction, but an increase in 1 SD of the relative abundance of and were associated with a 17% (95% CI=1.11-1.24) and 11% (95% CI=1.06-1.16) increase in mortality risk, respectively. Compared to participants with no detectable , participants in the highest tertile of had decreased mortality risk (HR=0.54; 95% CI=0.40-0.74).
Some measures of the oral microbiome were associated with all-cause mortality in this representative population cohort. These results suggest that oral bacterial communities may be important contributors to health and disease.
包括牙周病在内的口腔健康状况不佳与口腔微生物群变化及死亡风险增加有关。然而，尚无大型研究评估口腔微生物群是否与死亡率直接相关。
评估口腔微生物群指标是否与全因死亡率存在前瞻性关联。
一项横断面调查，于2009年至2012年收集样本，并通过2019年与受限使用的国家死亡指数（NDI）进行死亡率关联。
2009年至2012年的国家健康与营养检查调查（NHANES），这是美国人口的多阶段概率样本。
年龄在20至69岁之间、有资格与NDI进行关联并提供口腔冲洗样本的NHANES参与者（N = 7721，代表约1.94亿人）。
通过对口腔冲洗样本中提取的DNA的16S rRNA基因的V4区域进行测序来确定口腔微生物群。使用DADA2和QIIME生成α多样性、β多样性和属水平数据。
全因死亡率。
平均8.8年后，共有426名参与者死亡。使用Cox比例风险回归并在适当控制多重比较后，连续α多样性与全因死亡率呈负相关，但仅香农 - 维纳指数在对主要风险因素进行完全调整后具有显著关联（每标准差[SD]的风险比[HR]=0.85；95%置信区间[CI]=0.74 - 0.98）。来自Bray - Curtis差异矩阵的主坐标分析（PCoA）向量2（每SD的HR = 0.83；95% CI = 0.73 - 0.93）和来自加权UniFrac的PCoA1（每SD的HR = 0.86；95% CI = 0.75 - 0.98）在完全调整后与全因死亡率显著相关。在Bonferroni校正后，在属水平观察到的关联较少，但和相对丰度每增加1个SD分别与死亡风险增加17%（95% CI = 1.11 - 1.24）和11%（95% CI = 1.06 - 1.16）相关。与未检测到的参与者相比，处于最高三分位数的参与者死亡风险降低（HR = 0.54；95% CI = 0.40 - 0.74）。
在这个具有代表性的人群队列中，一些口腔微生物群指标与全因死亡率相关。这些结果表明口腔细菌群落可能是健康和疾病的重要影响因素。
