I’ve heard of probiotics, but what are they?
Probiotics in the strictest sense are living bacteria in a food or supplement designed to seed the gastrointestinal tract (GI) with bacteria. While any bacterium added to food could theoretically fall under this category, the term is typically reserved for bacteria considered beneficial in the colon. The Food and Agriculture Organization of the United Nations and World Health Organization have a joint definition for probiotics that encompasses just that:
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“Live microorganisms which when administered in adequate amounts confer a health benefit on the host”
- It must be a microorganism
- It must be viable upon delivery in the GI tract
- It must be consumed or administered via other means
- Must provide an adequate dose to observe health benefits
- Must transmit a health benefit
The International Scientific Association for Probiotics and Prebiotics (ISAPP) follows this definition as well, with minor grammatical edits to the statement. There are five core tenets of these definitions, listed in Box 1. Notably, this definition is widely considered the gold standard definition in industry and is often cited when determining if a new product falls within the probiotic category. It’s worth noting that there is no universal standard for what constitutes a benefit, and the burden of proof varies country to country. In the US specifically, probiotics are regulated as supplements by the Food and Drug Administration under the Federal Food, Drug, and Cosmetic Act. As such, these products are only allowed to be marketed using generalized structure/function claims. In the absence of disease-related claims, the regulation is focused on the legitimacy of claims, rather than efficacy, safety, and quality. The term “probiotic” itself is not a regulated term in the US. However, in Europe, it is a regulated term, and the use of the word “probiotic” on packaging labels was disallowed in 2013.
Typically, bacteria marketed as probiotics are isolated from the colonic tracts of humans or fermented foods, where the endogenous nature of the source lends to the safety of the product. You can read about the history of probiotics (before they had a name!) here and here. Many probiotics across multiple genera have been granted GRAS status (generally recognized as safe) including Bifidobacterium bifidum BGN4, Lactobacillus rhamnosus LGG, and Bacillus coagulans GBI-30, among others. While most common currently-available probiotics belong to the genera Lactobacillus, Bifidobacterium, Acidophilus, Bacillus, and Saccharomyces, there is substantial diversity both within and among genera. While the vast majority of studies have reported no or beneficial effects of probiotics, some negative effects have been documented. These are more likely in already vulnerable groups, like those with a preexisting disease. For example, in a randomized control trial of multi-strain probiotic use in individuals with predicted severe pancreatitis, 5% of the patients in the treatment group died compared to none in the placebo group. While rare, these adverse events have been reported and highlight the need for safety trials.
One reason for the diversity of products on the market is because not all strains have the same health benefits. There is a high specificity in the efficacy of a strain (or a combination of strains) on the observable impacts on health or disease. For example, while Saccharomyces boulardii CNCM I-745 is effective in treating irritable bowel syndrome, S. cerevisiae CNCM I-3856 is not. While Lactobacillus rhamnosus GG is effective in reducing the incidence of antibiotic-associated diarrhea in children, it is not effective for the prevention of traveler’s diarrhea.
Dose is key
One key factor in defining a probiotic is the amount ingested, which must be adequate to confer the health benefit. The effective dose depends on both the strain of the probiotic and the use in question. For example, a review on effective doses of various probiotics determined that of the 26 papers available on necrotizing enterocolitis (NEC), a severe and often fatal disease of preterm neonates, the unanimous conclusion was that additional work is needed to determine optimally efficacious doses, despite testing different probiotics across studies. Additionally, there does not appear to be a dose-response for any currently available probiotic for NEC. Contrastingly, a meta-analysis on the impacts of probiotics for the treatment of hypertension determined that a minimum effective dose of 1.0 x 1011 colony forming units (CFU) per day was needed to observe a significant reduction in blood pressure across nine studies evaluating various taxa. The minimum required dose is defined in some markets, for example, regulations in Italy and Canada require a minimum dose of 1.0 x 109 CFU for any probiotic.
A wide variety of formats for probiotic delivery are currently available in the market, including spores in a vial, sachets of powder, premixed beverages, capsules, lozenges, yogurt, and suppositories, among others. You can read an excellent review of the currently available probiotic products in a variety of countries here. Because a probiotic must maintain its viability and efficacy for the length of its shelf-life, several factors must be taken into consideration in the creation of probiotic-containing products, especially those with shelf lives of one year or more. Water content and activity are of particular concern in the long-term preservation of probiotics. Thus, lyophilization (freeze-drying) is a commonly used manufacturing technique for extending shelf of live bacteria in foods and supplements.
How do they work?
ISAPP identified the mechanisms underlying the health benefits of probiotics to include normalization of gastrointestinal microbial communities, regulation of intestinal transit, competition for resources and binding sites for pathogenic species, and production of short chain fatty acids. Additionally, some species at some doses may also confer benefits such as increased intestinal barrier integrity, synthesis of vitamins, and/or provide neurological, immunological, and biochemical health benefits. This is believed to be dependent on both the strain(s) of probiotic (single strain vs. multi-strain) and the dose at which it is administered.
Do you have a probiotic that needs GRAS status or a new commensal you’d like to test? Let’s chat to help you find the best way forward!
About the author: Kimberly Lackey is a clinical research specialist who adds chili oil to all foods. At Traverse, she’s worked on everything from canned foods to dietary supplements, but considers microbiomes her bread-and-butter. She earned her PhD in Zoology at Washington State University where she studied milk composition and infectious disease. If you want to learn more, follow her and Traverse Science on LinkedIn, and connect with us at firstname.lastname@example.org.
About the company: Traverse Science is a nutrition consulting firm working with ingredient suppliers and consumer packages goods companies in the human and animal nutrition space. We work with clients to get science done, whether that means organizing and conducting a study, analyzing new or long-forgotten data, or writing a manuscript for peer review or guidance document for internal use. As teams change, time runs short, or projects pivot, we provide the muscle and the know-how to finish your nutrition science and get your projects out the door – whatever that means for you. We believe that science doesn’t have to be hard, and we’re here to make it easy.
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