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BACKGROUND AND AIMS Public interest in pre- , pro-, and synbiotic products is increasing because of interactions between gut microbiota and human health. Our aim was to describe non-food (from dietary supplements or medication) pre, pro-, and synbiotic use by U.S. adults and children and reported reasons. METHOD Using data from the National Health and Nutrition Examination Survey (NHANES), we text-mined dietary supplement and prescription medication labels and ingredients to identify pre-, pro-, and synbiotic products used in the past 30 days. We describe trends in use from 1999-2018 (n=101,199) and prevalence in 2015-2016 and 2017-2018 (n=19,215) by age groups, gender, ethnicity/race, education, income, self-reported diet and health quality, and prescription gastrointestinal medication use stratified by children (<19 years) and adults (19+ years). RESULTS Non-food pre-, pro-, and synbiotic use increased up to three-fold in recent cycles. Prevalence of use for all ages for prebiotics was 2.4% (95% confidence interval: 2.0, 2.9%), probiotics was 4.5% (3.5, 5.6%), and synbiotics was 1.1% (0.8%, 1.5%). Use was highest among older adults [8.8% (5.4, 13.3) among 60-69 years for probiotics], non-Hispanic Whites, higher educational attainment and income, more favorable self-reported diet or health quality, and concurrent prescription gastrointestinal medication use. The top reasons for use were for digestive health and to promote/maintain general health. Less than 30% reported using these products based on a healthcare provider recommendation. CONCLUSION One in twenty U.S. adults or children use non-food, pre-, pro-, or synbiotic products and use has sharply increased in recent years. Most individuals voluntarily take these products for general digestive or overall health reasons.