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. 2025 Mar 20;24(1):45.
doi: 10.1186/s12937-025-01104-w.

Association of the use of nonfood prebiotics, probiotics, and synbiotics with total and cause-specific mortality: a prospective cohort study

Luyan Zheng  1 , Jiaqi Zhang  2 , Jing Yang  1 , Yanbo Wang  1 , Yina Zhang  1 , Kailu Fang  1 , Jie Wu #  3 , Min Zheng #  4
Affiliations

Association of the use of nonfood prebiotics, probiotics, and synbiotics with total and cause-specific mortality: a prospective cohort study

Luyan Zheng et al. Nutr J. .

Abstract

Background: The use of nonfood prebiotics, probiotics, and synbiotics has approximately tripled in the last 20 years. It is necessary to examine the associations of these substances with all-cause and cause-specific mortality in a large prospective cohort.

Methods: This study included 53,333 adults from the National Health and Nutrition Examination Survey 1999-2018. All participants answered questions on the use of dietary supplements and medications, including prebiotics, probiotics, and synbiotics. Death outcomes were determined by linkage to National Death Index records through 31 December 2019. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality from all causes, heart diseases, cancer, and other causes.

Results: During a mean follow-up of 10.6 years, 9117 deaths were documented, including 2364 heart disease deaths, 1964 cancer deaths, and 4700 other causes deaths. Compared to nonusers, nonfood prebiotic, probiotic, and synbiotic users had a 59% (HR 0.41, 95% CI 0.30 to 0.56), 56% (HR 0.44, 95% CI 0.26 to 0.74), 49% (HR 0.51, 95% CI 0.31 to 0.83), and 64% (HR 0.36, 95% CI 0.23 to 0.59) for lower risk of all-cause, cancer, heart disease, and other causes mortality, respectively. Moreover, the inverse association of the use of prebiotics, probiotics, and synbiotics with mortality was stronger in female participants and participants without hypertension.

Conclusion: The use of nonfood prebiotics, probiotics, and synbiotics is significantly associated with lower all-cause mortality, as well as deaths from heart disease, cancer, and other causes.

Keywords: Mortality; Nonfood; Prebiotics; Probiotics; Synbiotics.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study protocol for the US NHANES was approved by the US NHANES institutional review board and National Center for Health Statistics Research ethics review board. Institutional review board approval was waived for this analysis because of the publicly available and deidentified data. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of study participant selection and exclusion. Abbreviations: NHANES, National Health and Nutrition Examination Survey; MEC, Mobile Examination Center
Fig. 2
Fig. 2
Subgroup analyses of the associations of prebiotic, probiotic, and synbiotic use with all-cause mortality risk (users vs. nonusers). All estimates accounted for complex survey design of NHANES. Risk estimates were adjusted for baseline age (not adjusted in subgroup analysis by age), sex (not adjusted in subgroup analysis by sex), race/ethnicity, education level, marital status, family income-poverty ratio, smoking status (not adjusted in subgroup analysis by smoking status), drinking status (not adjusted in subgroup analysis by drinking status), BMI (not adjusted in subgroup analysis by BMI), physical activity level (not adjusted in subgroup analysis by physical activity), family history of diabetes and heart attack, self-reported general health, HEI (not adjusted in subgroup analysis by HEI), self-reported chronic diseases (not adjusted in subgroup analysis by diabetes or hypertension), fiber intake (not adjusted in subgroup analysis by fiber intake), and yogurt consumption (not adjusted in subgroup analysis by yogurt consumption). Abbreviations: CI, confident interval; BMI, body mass index; HEI, healthy eating index
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