Safety of Probiotics to Reduce Risk and Prevent or Treat Disease: Evidence Report/Technology Assessment Number 200

Probiotics (literally, "for life") are bacteria or yeasts considered to confer a health benefit on the host organism. This review addresses the safety of probiotics used in research to reduce the risk of, prevent, or treat disease. The review objective was to catalog what is known about the safety of interventions containing organisms from six different genera used as probiotic agents (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus), alone or in combination, used to reduce the risk of, prevent, or treat disease in research studies. This evidence report has a broad scope and was not restricted to specific interventions, specific patient groups, or specific clinical outcomes. The large number of included studies allowed unique analyses to explore adverse events reported to date in research on probiotics. The definition of what is a probiotic has evolved as the sciences of microbiology, medicine, and the manufacturing industries have matured. According to one definition offered by an expert committee convened by the Food and Agriculture Organization of the United Nations and the World Health Organization, probiotic organisms are live microorganisms that when administered in adequate amounts confer a health benefit on the host (FAO/WHO, 2001). This definition explicitly restricts what can be considered a probiotic to live organisms. Other definitions do not emphasize the viability of the microorganisms and would include heat-killed preparations (e.g., Salminen, Ouwehand, Benno, & Lee, 1999). Defining probiotics is challenging because of the limits in our understanding of how organisms benefit the human host, the apparent variation in what may constitute a beneficial balance for digestion and other physiological processes, the effects of probiotic organisms on the normal gut environment, and our limited understanding of the gut ecosystem (Schmid, 2006). The review set out to answer a number of research questions posed by the sponsors of the evidence review. Key questions include: Key Question 1. What is the evidence that the active and lyophilized forms of probiotics (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus) as single ingredients or in combination with other probiotics or prebiotics in all delivery vehicles (and formulations) when used to cure, treat, mitigate, or prevent a disease or reduce disease risk are safe in the short term? In the long term? Key Question 2. What are characteristics and associations of the reported harms in Question 1? Key Question 3. What is the evidence that harms of Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus differ by product and delivery characteristics? Key Question 4. How do the harms of Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus vary based on dose; (b) timing; (c) mode of administration; (d) age, gender, ethnicity, disease or immunologic status; (e) relationship to efficacy? Key Question 5. How often does harm associated with Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus lead to hospital admission or lengthened hospitalization? Key Question 6. How does harm associated with Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus relate to use of concomitant antibiotics, confounding diet therapies, corticosteroid use, immune suppressants, or other potential confounders?