Oral microbiome alpha diversity and all-cause, cardiovascular, and non-cardiovascular mortality in US adults: Evidence from the NHANES 2009-2019

Rajib Mondal; Rani Baroi Ritu; Kaori Kitaoka; Nazar Mohd Azahar; Mohammad Moniruzzaman; Soshiro Ogata; Eri Kiyoshige; Haruka Tohara; Yusuke Kobayashi; Naoki Kashihara; Toshio Naito; Naoki Nakashima; Kosuke Tamura; Kunihiro Nishimura; Anthony J Viera; Yuichiro Yano

doi:10.1016/j.atherosclerosis.2024.119074

Oral microbiome alpha diversity and all-cause, cardiovascular, and non-cardiovascular mortality in US adults: Evidence from the NHANES 2009-2019

Atherosclerosis. 2024 Nov 29:401:119074. doi: 10.1016/j.atherosclerosis.2024.119074. Online ahead of print.

Authors

Rajib Mondal¹, Rani Baroi Ritu², Kaori Kitaoka³, Nazar Mohd Azahar⁴, Mohammad Moniruzzaman⁵, Soshiro Ogata⁶, Eri Kiyoshige⁶, Haruka Tohara⁷, Yusuke Kobayashi⁸, Naoki Kashihara⁹, Toshio Naito¹⁰, Naoki Nakashima¹¹, Kosuke Tamura¹², Kunihiro Nishimura⁶, Anthony J Viera¹³, Yuichiro Yano¹⁴

Affiliations

¹ Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science, Shiga, Japan; Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
² Department of Preventive Medicine, NCD Epidemiology Research Center, Shiga University of Medical Science, Shiga, Japan.
³ Department of Advanced Epidemiology, NCD Epidemiology Research Center, Shiga University of Medical Science, Shiga, Japan.
⁴ NCD Epidemiology Research Center, Shiga University of Medical Science, Shiga, Japan; Faculty of Health Sciences, Universiti Teknologi MARA, Cawangan Pulau Pinang, Kampus Bertam, Pulau Pinang, Malaysia.
⁵ NCD Epidemiology Research Center, Shiga University of Medical Science, Shiga, Japan; Socio-Spatial Determinants of Health (SSDH) Laboratory, Population and Community Health Sciences Branch, Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.
⁶ Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
⁷ Department of Dysphagia Rehabilitation, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
⁸ YCU Co-Creation Innovation Center, Yokohama City University, Yokohama, Japan.
⁹ Kawasaki Geriatric Medical Center, Kita, Okayama, Japan.
¹⁰ Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
¹¹ Medical Information Center, Kyushu University Hospital, Japan.
¹² Socio-Spatial Determinants of Health (SSDH) Laboratory, Population and Community Health Sciences Branch, Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.
¹³ Department of Family Medicine and Community Health, Duke University, NC, USA.
¹⁴ Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan; Department of Family Medicine and Community Health, Duke University, NC, USA. Electronic address: yano.yuichiro@jichi.ac.jp.

PMID: 39644613
DOI: 10.1016/j.atherosclerosis.2024.119074

Abstract

Background and aims: Knowledge about the association between oral microbiome diversity within individuals and cardiovascular disease (CVD) and non-CVD mortality is scarce. Besides, variation by sex and racial and ethnic groups, and the potential mediators of these associations remain unclear. We aimed to investigate the associations of oral microbiome alpha diversity with all-cause, CVD, and non-CVD mortality, and the interaction effects of sex and racial and ethnic groups and potential mediators in the associations.

Methods: The National Health and Nutrition Examination Survey (NHANES) is a population-based observational study, conducted periodically in Mexican American, Other Hispanic, Non-Hispanic (NH) White, NH Black, and other racial/ethnic participants. We linked 2009-12 survey data of 8199 adults to the mortality data until 2019. By analyzing RNA gene sequences from oral rinse samples, microbiome alpha diversity within individuals was assessed using operational taxonomic unit (OTU) richness. Potential mediators included obesity, diabetes mellitus, dyslipidemia, hypertension, and periodontitis. Multivariable Cox proportional hazards regression and causal mediation analysis were used.

Results: Baseline mean ± standard deviation (SD) age was 42.1 ± 15.1 years. Over a median follow-up of 9.1 years, 405 all-cause mortality occurred (CVD, 105; non-CVD, 300). Each 1-SD increment in OTU richness was inversely associated with all-cause mortality (hazard ratio [HR] 0.92, 95 % confidence interval [CI] 0.90-0.95), CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95), and non-CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95). With evidence of significant racial and ethnic groups-interaction (p <0.05), these associations were evident in Mexican American, NH White, and others racial/ethnic participants. None of the potential mediators significantly mediated the associations of OTU richness with all-cause, CVD, and non-CVD mortality.

Conclusions: Lower oral microbiome alpha diversity is associated with higher risk for all-cause, CVD, and non-CVD mortality, and the associations are varied by racial and ethnic groups.

Keywords: All-cause mortality; Alpha diversity; Cardiovascular disease; Cardiovascular mortality; Non-cardiovascular mortality; Oral microbiome.