While longevity is a popular topic, it is mortality risk that truly matters. As aging research advances, both scientists and health professionals are placing greater emphasis on not only extending lifespan but also on minimizing the risk of death from chronic diseases. Although the prospect of living longer is appealing, the reality of mortality, how we experience death, remains the primary concern.

Among the many interventions being explored, the gut microbiome remains a central focus of attention. Decades of research suggest that prebiotics, probiotics, and synbiotics from dietary sources are associated with improved health and reduced mortality. But what about supplements? As grocery and pharmacy shelves are increasingly stocked with capsules and powders—and as personalized protocols become more common—a new question emerges: Can biotics taken in supplement form provide similar benefits to those from fresh food?

This IPA blog focuses on the latest large-scale epidemiological studies linking biotic supplements—not food—to reduced mortality risk, and explores the implications of these findings. 

Probiotic: Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.

Prebiotic: A substrate that is selectively utilized by host microorganisms conferring a health benefit.

Synbiotic: A mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host.

Biotics from fresh food and mortality, briefly

Before diving into the latest data on supplements, it’s worth noting that decades of observational research have linked food-based prebiotics, probiotics, and synbiotics—particularly those from fiber-rich and fermented foods—with lower mortality. Researchers have also explored how these biotics and various dietary strategies influence the gut microbiota, especially as it changes with aging or in the context of age-related diseases.

For example, higher total dietary fiber intake—especially from vegetables and soluble sources—was associated with a lower risk of all-cause mortality in a Mediterranean cohort of 19,703 participants. 

A 2025 study, using data from the National Health and Nutrition Examination Survey (NHANES) 2003-2018, found that dietary intake of live microbes was linked to reduced all-cause and cardiovascular mortality in an older U.S. population.

FYI: NHANES is an ongoing nationwide survey that collects data on the health and nutritional status of adults and children in the United States. It combines interviews and health examinations to gather information on a wide range of topics including extensive dietary, supplement, and health outcomes, making it a valuable resource for research. 

In the above study, which included 7,882 participants, older adults with high dietary live microbe intake had 18% lower all-cause mortality and 23% lower cardiovascular mortality. 

Thus, while food-based biotics have been associated with lower mortality, emerging evidence suggests that supplements containing prebiotics, probiotics, and synbiotics may offer similar benefits.

Biotics from supplements, and mortality

Probiotic supplementation has shown promising potential for reducing mortality, particularly in experimental animals. 

Animal models

Mice: Bifidobacterium animalis subsp. lactis increased survival and reduced inflammation and age-related gene expression. 

Caenorhabditis elegans (a worm model for many aging studies): various probiotic strains extend lifespan through mechanisms such as dietary restriction, serotonin signaling, oxidative stress resistance, and modulation of insulin-like and immune pathways.

Drosophila melanogaster(common fruit fly): a multi-strain probiotic blend improved longevity by managing insulin resistance, energy metabolism, and inflammation. 

Humans 

Given the physiological complexity and extended lifespans of humans compared to these animals, it is impossible to directly research whether biotic supplements may reduce mortality. A new approach, similar to that pursued when studying the effect of dietary sources of biotics on mortality, resulted in useful data on supplements. Once again using the trove of data from NHANES, the 2025 study of 7,882 individuals observed that prebiotic and probiotic supplement intake was associated with a reduced risk of mortality in an older U.S. population.

In a more expansive 2025 study, data was analyzed from 53,333 adults in the NHANES 1999–2018 dataset, all of whom answered questions about their use of dietary supplements and medications, including prebiotics, probiotics, and synbiotics. 

A small portion of the population—1.6%—reported using biotic supplements in the previous month. These users were more likely to be older, female, non-Hispanic white, well-educated, and physically active. Over a 10.6-year follow-up, their use was associated with significantly lower all-cause, heart disease, and cancer mortality after adjusting for key confounders (including demographics, lifestyle factors, comorbidity conditions, and intake of prebiotics and probiotics from food). Notably, compared to nonusers, those taking prebiotics, probiotics, or synbiotics had a higher prevalence of cancer at baseline. This diagnosis may have prompted them to adopt healthier behaviors, as these individuals also reported better diet quality and greater fiber intake—factors that were adjusted for in the analysis.

Specifically, compared to nonusers, individuals who used biotic supplements had a significantly 59% lower risk of all-cause mortality, 56% lower heart disease mortality, 49% lower cancer mortality, and 64% lower other causes of mortality.

The researchers noted that the inverse relationship between biotic supplementation and mortality was stronger in females, possibly due to estrogen’s influence on gut microbiota. Estrogen has been shown to shape microbial diversity and function, including the activity of β-glucuronidase-producing bacteria, which in turn affects systemic estrogen levels and may impact disease risk.

The association was slightly weaker in participants with hypertension, suggesting a complex interaction involving the gut microbiota. 

The authors noted several strengths, including the use of a large, nationally representative sample and long-term follow-up. However, limitations included the inability to determine causality, the absence of dose-response data, and potential confounding factors.

Mechanisms

Several mechanisms may explain the inverse associations of biotic supplements with mortality. Biotic supplementation may:

  • Restore microbial balance
  • Inhibit harmful pathogens
  • Strengthen gut barrier function
  • Enhance immune function
  • Reduce systemic inflammation 
  • Reduce age-related inflammation (inflammaging)
  • Counteract environmental toxins

These dynamics can lead to beneficial outcomes relevant to chronic disease prevention and reduced mortality risk. For example, by restoring microbial balance and strengthening gut barrier function, certain biotics can improve lipid and glucose metabolism. A 2024 systematic review and meta-analysis encompassing 41 randomized controlled trials found that gut microbiota-targeted interventions—such as probiotics, prebiotics, and synbiotics—significantly reduced fasting glucose, HbA1c, insulin resistance, total cholesterol, LDL cholesterol, and triglycerides, while modestly increasing HDL cholesterol. 

Additionally, the fermentation of prebiotics by gut bacteria produces short-chain fatty acids that support metabolic health. Through the gut-brain axis, modulation may also affect stress, which can indirectly improve metabolic function and lower the risk of chronic diseases such as cardiovascular disease and type 2 diabetes.

Together, these findings highlight the potential of biotic supplements to modulate key biological pathways involved in metabolic health and chronic disease prevention.

Takeaway

While food-based sources of prebiotics, probiotics, and synbiotics have long been linked to improved health and reduced mortality, new evidence suggests that supplements may offer similar benefits. Recent large-scale U.S. studies indicate that even low levels of supplement use are associated with significantly lower risks of death from all causes, including heart disease and cancer—particularly in older adults and women. Though more research is needed to confirm causality and optimal dosing, these findings open the door to broader conversations about the role of microbial support in healthy aging.

Key references

The International Probiotics Association (IPA) is a global non-profit organization that advocates for the safe and efficacious use of Pre-, Pro- and Post- biotics. The association brings together the knowledge and resources of scientists, healthcare professionals, academics, and regulators to define clear standards that advance the quality of these biotic categories around the world. Holding NGO status before Codex Alimentarius and observer status at ISO, the IPA is also recognized as the unified “Global Voice of Pre-, Pro- and Post- biotics®” around the world. For more information visit: https://internationalprobiotics.org/home/

Clare Fleishman, MS RDN, bridges the gap between science and health across most platforms: major newspapers, magazines, books (Globesity), workshops, social media, and websites. In 2010, she launched ProbioticsNow.org to share the cascade of new discoveries in the microbiome. Always amazed at this "forgotten organ," Fleishman has also created white papers, blogs, videos, and social media for the International Probiotics Association. She recently published Fertility: Why Microbes, Weight & Nutrition Matter.