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Probiotics 101

Curious about probiotics? This article explains what probiotics are, how probiotics work, what specific strains of probiotics have been studied for, and how you can choose the right probiotic.

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Contents

Introduction

What are probiotics?

How do probiotics work?

What are probiotics good for?

Choosing a Probiotic

Q&A

Further Reading

Citations

Every day, people send us photos of the probiotics they’re taking and the labels of microbe-packed kimchi they’re eating. They text us with Amazon links before they place an order and with recommendations from their chiropractor. We hear dozens of well-meaning questions and misconceptions about probiotics before we arrive at the office (or the lab bench, depending on the day).

As scientists committed to improving human health with microbes, we appreciate all the thoughtful inquiry. There’s so much to consider when getting started with a probiotic, from understanding how scientists define the term “probiotic,” to how probiotics work inside your gastrointestinal tract, to what benefits you can expect and when you might see and feel them.    

We’re here to clarify the FAQs and debunk some common myths around what probiotics are, what they do, and why you may want to give them a try.

Definitions

Common terms you’ll encounter while choosing a probiotic.

Definitions

Probiotic: A microorganism that is alive and administered in the dosage clinically studied to confer a health benefit in the host (that’s you!).

Microbe: Any sort of microscopic organism, or microorganism, including bacteria, archaea, protists, fungi, and viruses. 

Clinical Study: Research studies performed on people to evaluate an intervention, like finding out if a probiotic is safe and effective for helping with digestive issues.

Bacteria: A prokaryotic, or unicellular (and having no cell nucleus or other membrane-bound organelle) organism. Probiotics are usually bacteria, but not always.

CFU: The Colony Forming Unit (CFU) is a measure of the number of cells that remain viable enough to proliferate and form small colonies.

AFU: Active Fluorescent Units (AFU), measured through flow cytometry, is a process where probiotic cells are tagged with fluorescent “markers” and counted by a laser as they pass through a tube. AFU allows for a precise measurement of all living cells, including ones that are efficacious but wouldn’t be counted using the CFU technique.

SHIME®: Simulator of the Human Intestinal Microbial Ecosystem. A model of human digestion that recreates the physiological conditions and biological processes (food uptake, peristalsis, digestive enzymes, pancreatic and bile acids, and time spent in each stage of digestion) representative of the human gastrointestinal tract.

How does science define a ‘probiotic’?

The term “probiotic” is used loosely by marketers, media, and even some scientists, often applied to anything with the presence of a microbe. This is only part of the picture — and it’s important that we get it right. Why? Because the potential for beneficial microbes to improve health and even the environment is substantial. 

The scientific field is growing, with only 760 papers about probiotics prior to 2001 and over 36,000 studies with “probiotic” in the title as of early 2022.1 The commercial market is growing, too, with sales of probiotics over $40 billion and projected to reach over $64 billion by 2023.2 Being clear about what probiotics are helps the field maintain scientific credibility and helps customers find trustworthy products with proven benefits.  

Fortunately, we have an official definition of “probiotics,” which was first authored by a 2001 UN/WHO expert panel (chaired by our Chief Scientist, Dr. Gregor Reid) and then revised in 2014.3 It defines probiotics as follows: “Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” Let’s break that down into its component parts using the help of a review that our former Director of Research + Development, Dr. Azza Gadir, and Co-Founder Raja Dhir co-authored, along with Dr. Gregor Reid in the scientific journal Frontiers in Microbiology.4

 

Live microorganisms

The microbes in your probiotic must be alive in the stated quantities (AFU or CFU) at the time you consume them. That means they have to survive through processing, shipping, and the time they sit in their packaging before they are taken by you. This in mind, we engineered our ViaCap™️  2-in-1 capsule delivery technology—which nests our probiotic inner capsule inside a prebiotic outer capsule, protecting the bacteria from oxygen, moisture, heat, light, and even stomach acid. 

We’ve done extensive testing to confirm the bacteria in the DS-01™ Daily Synbiotic stay alive throughout their journey—ensuring viability at room temperatures for 18 months past manufacturing, over 10 days at constant 100°F exposure, and even 2 days at continuous 120°F.

Bonus: we take it one step further and verify that our probiotics survive digestive conditions as well. We test using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®)—a model of human digestion that recreates the physiological conditions and biological processes (food uptake, peristalsis, digestive enzymes, pancreatic and bile acids, and time spent in each stage of digestion) representative of the human gastrointestinal tract. This technology shows that our ViaCap™️ delivers our probiotic strains—100% alive and well—through the end of the small intestine for delivery into the colon, where their real work begins.

 

Delivered in adequate amounts

The microbes in a probiotic must be alive, yes, but also in an adequate number when administered. The number of the microbes in a probiotic dose will be listed on the label, measured in either CFU (colony forming units) or, our preferred method, AFU (active fluorescent units). This amount should match the dosage used in the corresponding clinical trial demonstrating the benefit of the particular bacterial strain. 

 

Strain specificity 

Bacterial strains must be identified genetically, classified using the latest terminology, and designated by numbers, letters, or names. On the Seed label, that looks like this: Bifidobacterium breve SD-BR3-IT. With at least 254 different Bifidobacteria, identifying the correct one is important.5 

 

Proven health benefits 

Appropriately sized and designed studies must be performed to evaluate the effect of the specific strain(s) on the host (that’s you) for which the probiotics are intended. Only once a bacteria has demonstrated a concrete health benefit in a given host, may it then be designated a “probiotic.” 

 

Dedicated clinical studies

Strains shown to be beneficial for one condition in a given host may not be helpful for another application or a different species of host. For example, a probiotic shown to have a benefit for irritable bowel syndrome in humans may not address antibiotic-associated diarrhea, and likewise can’t be assumed to help with your dog’s GI problems. In other words, we can’t make any assumptions about translatability of benefits until they are shown in a dedicated clinical study, in the target host population, horse, human, or hound.

How do probiotics work?

Okay, so let’s say you’ve got your hands on a probiotic that meets all the relevant scientific criteria. You take it. What happens next? How does a capsule full of living microorganisms set in motion a process that benefits your health?

We first need to clear up a common misconception: that probiotics have to colonize your gut and alter the composition of your microbiome to be effective. That’s not true. Probiotics typically don’t take up residence in your gut. Compared to the tens of trillions of microbes already rooted in your intestinal tract, most probiotics don’t contain enough new bacteria to make a significant difference in the composition of your microbiota.

Even if they did, we don’t know enough about the safety of introducing colonizing microbes. Large numbers of newcomers moving in and displacing your existing bacteria could alter the unique balance of your ecosystem within and trigger unintended consequences.

What scientists do know is that, as transient microbes, probiotics travel through your intestines, interacting with your immune cells, gut cells, dietary nutrients, and existing bacteria to, directly and indirectly, deliver benefits like these: 

  • Gut barrier integrity: Some enhance the gene expression involved in tight junction signaling, which improves the integrity and selective impermeability of the intestines—this means a tight gut barrier.
  • Neurotransmitters: Others can trigger the production and release of neurotransmitters that stimulate muscle contractions for increased gastrointestinal motility—think, better, easier poops.
  • Metabolic and immune health: Yet other bacteria produce byproducts like short-chain fatty acids (SCFAs), which have been extensively shown to be beneficial for metabolic and gut immune health.

Now we’re talking about the benefits of probiotics. If you ingest billions of transient microbes and they help enhance gene expression or create SCFAs, what’s in it for you? Probiotic strains can impact your health everywhere from your gastrointestinal tract to your skin to your heart. Let’s take digestion as an example, since 61% of Americans suffer from digestive discomfort.6

Much of what we do contributes to our digestive health: what and when we eat,7 our hydration, how much (soluble and insoluble) fiber we get, our response to stress and anxiety, the quality and duration of our sleep, how much exercise we get, and our indulgence in choices like caffeine and alcohol. Many other perturbations of modern life can also disrupt your gut microbiome, for example, antibiotics and analgesic over the counter drugs like aspirin and ibuprofen.8,9

Probiotic strains have been studied extensively in clinical trials to support digestion and gastrointestinal function. For example, in a 300-person study, researchers discovered that two specific strains (Lactobacillus plantarum SD-LP1-IT and Bifidobacterium breve SD-BR3-IT) supported gastrointestinal functions in people with digestive issues.10 These strains supported healthy regularity, stool consistency, bowel movement comfort, and ease of bloating. 

That’s because these bacteria perform critical functions like the production of SCFAs we mentioned — particularly acetate, propionate, and butyrate — that support wave-like muscle contractions in the intestines in order to facilitate bowel movements.

How should you choose a probiotic?

Deciding on a probiotic isn’t as simple as picking one with the highest CFU count. Here are several other things to consider:

Origin: Does the probiotic come from humans or is it derived from soil or animals?

Species and Strain: Lactobacillus acidophilus is different from Lactobacillus rhamnosus, and within each species there can be hundreds or thousands of strains. As we’ll explain later, one could be beneficial for a specific condition and another could be harmful. 

Testing: Was the specific strain shown to confer a live microbe-mediated health benefit, as evidenced in clinical studies?

Potency: You’ve probably seen CFU on labels. CFU refers to colony-forming units, which basically tells you how many bacteria in the sample are capable of dividing and forming colonies. A bigger number on the bottle does not always mean better results. The best dose, per strain, is the one that has been studied in humans and shown to deliver positive outcomes. 

And CFU has become a marketing tool. Many probiotics today proclaim outrageously enormous CFU counts, but are unable to survive the trip from manufacture to store shelf, much less the journey from your mouth, through your acidic digestive process, to your gut. Oftentimes, to get around this, the number on the box will refer to “time of manufacture,” when really, it should tell you what amount will still remain viable near the expiration date.

More interestingly, a new form of measurement has emerged that you can keep an eye out for: AFU. AFU stands for Active Fluorescent Units. It’s measured with flow cytometry, a process where probiotic cells are tagged with fluorescent “markers” and counted by a laser as they pass through a tube. Through AFU, we are able to calculate a more precise measurement of all viable cells, including ones that are efficacious but not necessarily culturable (and therefore would not be counted in a traditional plated CFU measurement).

Survivability and Viability: The stomach is an inhospitable place: hydrochloric acid, potassium chloride, sodium chloride — mucus, too. You can imagine that this destructive environment presents quite an obstacle course for living microbes in our food or dietary supplements, which need to make their way through the stomach and small intestine alive, in order to carry out their full range of fermentative functions in the colon. 

The realities of the human digestive system should be considered in developing probiotics, which is possible using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), a model of human digestion that recreates the physiological conditions and biological processes (food uptake, peristalsis, digestive enzymes, pancreatic and bile acids, and time spent in each step) representative of the human gastrointestinal tract. (Our Daily Synbiotic, with its 2-in-1 capsule technology, protects against stomach acid and safeguards the viability of 53.6 billion probiotic bacteria through digestion, delivering 100% of the starting dose of the live bacteria to the end of the small intestines and into the colon.)

What is the best time to take a probiotic?

Now that you know what to consider when choosing a probiotic, when should you take it? The time of day is less important than understanding that you ideally want to take a probiotic on an empty stomach (and at least 15-45 minutes before a meal, or 2-3 hours after eating). For most people that means first thing in the morning or right before bed. Why take it on an empty stomach? As we suggested in the “survivability and viability” consideration above, stomach acid is potentially harmful to living microbes, and as you might expect, having food in your stomach means more stomach acid and bile is released, making it a more challenging environment to pass through. However, we also acknowledge that each person is unique, and what’s ideal for probiotic survival may not be ideal for your needs. You know your body best—we recommend trying to find a time to take your probiotic that works best for your particular ecosystem. Consistent, daily intake is the most important thing.

 

How long does it take for probiotics to work?

Let’s refer back to the section in which we discussed how probiotics work and remember that different strains have been clinically studied for different benefits, so the answer will be different for each strain and its particular dosage. In the 300-person study on Lactobacillus plantarum SD-LP1-IT and Bifidobacterium breve SD-BR3-IT, participants experienced significant benefits to their digestive health within 15 days. Those are fast-acting microbes.

 

What are the signs probiotics are working?

Again, this will depend on the strain and its associated benefits. For participants in the 300-person study on Lactobacillus plantarum SD-LP1-IT and Bifidobacterium breve SD-BR3-IT, the signs were pretty clear. This combination of strains supported healthy regularity, stool consistency, bowel movement comfort, and ease of bloating.

 

Who invented probiotics?

Nobel Prize-winning embryologist Élie Metchnikoff is generally regarded as having started the modern scientific field of probiotics. In the 1910s through the 1930s, gastrointestinal issues were treated with Lactobacillus acidophilus based on the work of Metchnikoff and Yale bacteriologist Leo Rettger.11 The term “probiotics” emerged later, between the 1950s and the 1970s, and in the 1980s it was used routinely in medical and veterinary literature to describe live organisms that were introduced to improve the host microbial balance.

 

I’ve heard a lot about probiotic foods and drinks. Can I just eat kimchi, or drink kombucha?

Kimchi and kombucha are fermented foods, not probiotics, and it’s important as a consumer to understand that the terms aren’t interchangeable. Fermented foods, as defined in a recent consensus statement by scientists at the International Scientific Association for Probiotics and Prebiotics (ISAPP), are “foods made through desired microbial growth and enzymatic conversions of food components.”12 That’s quite different from the definition we gave above (and reiterated in the consensus statement) of probiotics, which suggests that the term probiotic is specifically used when there is a demonstrated health benefit conferred by a specific dosage of well-defined and characterized live microorganisms.  

It is possible that many “probiotic” foods and beverages like kimchi and kombucha contain beneficial bacteria—yet because they have not been subjected to controlled studies in humans and demonstrated a health benefit beyond the food or beverage itself, they do not meet the internationally recognized definition of a probiotic.

That’s why the scientists who wrote the consensus paper offered a set of terms they suggest using on labels to distinguish between different products and the claims they make about probiotics. You probably won’t see these on labels anytime soon, but take note of them so you can make more informed purchases at the grocery store.

 

Four ways of defining fermented foods:

  • Probiotic fermented food: A product with “evidence of a strain-specific benefit from a well-controlled intervention study…together with proven safety and confirmation of sufficient numbers of that strain in the final product to confer the claimed benefit.”
  • Contains probiotics: “At least one of the strains in the food meets the criteria implicit in the term probiotic and if the strain is a member of a well-studied species known to confer probiotic health benefits via the principle of ‘shared benefits.’”
  • Contains live and active cultures: “Fermented foods and beverages that contain undefined microbial consortia, usually at variable levels, and their potential health benefits have generally not been demonstrated.”
  • Foods made by fermentation: Pasteurized fermented foods without live microorganisms in the final product.

Most foods sold commercially fall into the third and fourth categories. Some may have a health benefit related to the microbial content, but it’s just not possible to say without the rigorous scientific evidence that the first and second categories require. 

This is, of course, not to say that you shouldn’t eat or drink fermented food and drinks that fall into the latter two categories. Many fermented foods and beverages are extremely nutritious, not to mention very tasty, additions to your daily diet (though we do suggest keeping an eye out for excessive sugar content—as many commercial products like yogurts and beverages are sweetened with added sugars). The distinction is that they may not necessarily be reliable sources of beneficial, effective bacteria.

 

But my friend offered me some probiotic nuts the other day. What’s the deal with that?

Good question! And you could go buy some “probiotic” shampoo and mattresses too. Hopefully, by now, you understand that most of the products labeled “probiotic” out there are, unfortunately, not probiotic at all. Remember, to be probiotic, something has to fully satisfy the scientific definition disseminated by the World Health Organization, which we outlined above.

 

So, why are all these products allowed to say that they’re probiotic?

It’s a really, really good question.

In the United States, the Food and Drug Administration (FDA) categorizes probiotics as dietary supplements. Dietary supplements are marked by under-enforcement compared to drugs — similar to how speed limits exist everywhere but getting a speeding ticket is a rarity. As such, the term “probiotic” has been taken for marketing purposes, and much of the science has been lost in translation.

In fact, in almost all of Europe, it’s actually illegal to market something labeled as a probiotic, let alone make any claims. So while we, at Seed, certainly adhere to FDA regulations, we actually look to even higher global standards like the European Food Safety Authority (EFSA) and Japan’s Foods for Specified Health Uses (FOSHU) in the manufacture and translation of probiotics.

A few helpful articles and resources about probiotics:

Probiotics: Reiterating What They Are and What They Are Not: This is a review article co-authored by our Chief Scientist, Dr. Gregor Reid, and published in the scientific journal Frontiers in Microbiology. It articulates the scientific definition of probiotics and explains why it’s so important that we use it appropriately.

Probiotics: What You Need to Know: This helpful guide from the National Center for Complementary and Integrative Health at the National Institutes for Health (NIH) covers a lot of the same ground we covered here, but offers the unique perspective of our government’s scientists and researchers.

  1. NCBI. (2022). Pubmed.Gov. https://pubmed.ncbi.nlm.nih.gov/?term=probiotic
  2. Global Market Insights Inc. (2018, June 29). Probiotics Market Size to Exceed USD 64 Billion by 2023: Global Market Insights Inc. Cision PR Newswire. https://www.prnewswire.com/news-releases/probiotics-market-size-to-exceed-usd-64-billion-by-2023-global-market-insights-inc-578769201.html
  3. Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., Morelli, L., Canani, R. B., Flint, H. J., Salminen, S., Calder, P. C., & Sanders, M. E. (2014). The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology, 11(8), 506–514. https://doi.org/10.1038/nrgastro.2014.66
  4. Reid, G., Gadir, A. A., & Dhir, R. (2019). Probiotics: Reiterating What They Are and What They Are Not. Frontiers in Microbiology, 10. https://doi.org/10.3389/fmicb.2019.00424
  5. O’Callaghan, A., & van Sinderen, D. (2016). Bifidobacteria and Their Role as Members of the Human Gut Microbiota. Frontiers in microbiology, 7, 925. https://doi.org/10.3389/fmicb.2016.00925
  6. Almario, C. V., Ballal, M. L., Chey, W. D., Nordstrom, C., Khanna, D., & Spiegel, B. (2018). Burden of Gastrointestinal Symptoms in the United States: Results of a Nationally Representative Survey of Over 71,000 
  7. Singh, R. K., Chang, H. W., Yan, D., Lee, K. M., Ucmak, D., Wong, K., Abrouk, M., Farahnik, B., Nakamura, M., Zhu, T. H., Bhutani, T., & Liao, W. (2017). Influence of diet on the gut microbiome and implications for human health. Journal of translational medicine, 15(1), 73. 
  8. Blaser M. J. (2016). Antibiotic use and its consequences for the normal microbiome. Science (New York, N.Y.), 352(6285), 544–545. https://doi.org/10.1126/science.aad9358
  9. Rogers, M., & Aronoff, D. M. (2016). The influence of non-steroidal anti-inflammatory drugs on the gut microbiome. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 22(2), 178.e1–178.e9. https://doi.org/10.1016/j.cmi.2015.10.003
  10. Del Piano, M., Carmagnola, S., Anderloni, A., Andorno, S., Ballarè, M., Balzarini, M., Montino, F., Orsello, M., Pagliarulo, M., Sartori, M., Tari, R., Sforza, F., & Capurso, L. (2010). The use of probiotics in healthy volunteers with evacuation disorders and hard stools: a double-blind, randomized, placebo-controlled study. Journal of clinical gastroenterology, 44 Suppl 1, S30–S34. https://doi.org/10.1097/MCG.0b013e3181ee31c3
  11. Podolsky, S. H. (2012). Metchnikoff and the microbiome. The Lancet, 380(9856), 1810–1811. https://doi.org/10.1016/s0140-6736(12)62018-2
  12. Marco, M. L., Sanders, M. E., Gänzle, M., Arrieta, M. C., Cotter, P. D., de Vuyst, L., Hill, C., Holzapfel, W., Lebeer, S., Merenstein, D., Reid, G., Wolfe, B. E., & Hutkins, R. (2021). The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods. Nature Reviews Gastroenterology & Hepatology, 18(3), 196–208. https://doi.org/10.1038/s41575-020-00390-5