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Evidence Based

This article is based on scientific evidence, written by experts and fact checked by experts.

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This article contains scientific references. The numbers in the parentheses (1, 2, 3) are clickable links to peer-reviewed scientific papers.

Why Probiotic Biodiversity is More Important Than Strain

Written by Dr. Michael Ruscio, DC on January 8, 2024

Written by Dr. Michael Ruscio, DC on January 8, 2024 — Reviewed by Dr. Hannah Hamlin

Unpacking the Latest Research on Probiotic Strains, Dosing, and Efficacy

• Definitions: Category, Species, and Strains|
• Deconstructing the Research: Which Part Matters?|
• Probiotics are Fragile: Debunked|
• Simplicity Wins the Race|
• Find Your Minimum Effect Dose|
• What is the Best Probiotic Strain?|

You’ve likely landed here because you already know a bit about probiotics. You know that probiotics are live bacteria and fungi, that they live in fermented foods like yogurt and sauerkraut, and that they’re good for gut health. You’ve likely also noticed on the back of a probiotic supplement that there are billions of organisms in each capsule, and that different brands offer different species and strains of probiotics.

If you’ve come this far, it’s either because you’re curious about the difference between all those species and strains or because you have a particular health condition that you think may benefit from a specific type of probiotic. Before we address these curiosities, I’ll first say that asking the question, “What is the best probiotic strain?” might be a little off the mark.

While there’s a lot of research to support probiotic health benefits: boosting gut bacteria to improve digestive health, supporting the immune system, and even boosting mental health, there’s no research to support that any specific strain is the BEST at addressing these things.

Put succinctly, probiotics are not condition-specific.

Rather, what seems to lead to marked health benefits is biodiversity in the gut microbiome—different types of probiotics working symbiotically to enhance your overall health and wellness. In other words, the specific microbes don’t matter as much as consistently delivering a variety to your digestive system.

Let’s start with some definitions first, so we’re all on the same page. Then I’ll share the latest research about probiotics and debunk a few previously held beliefs. From there, I’ll briefly explain why the simplest method is usually the one that works best, and we’ll wrap up with how to find your minimum effective dose.

Definitions: Category, Species, and Strains

The best way to break down how probiotics are classified is to go from broad to specific. Category (which is based on genus) is the most broad. There are three categories:

Category 1: Lactobacillus/Bifidobacterium blends

Category 2: Saccharomyces boulardiiCategory 3: Soil-based, or Bacillus

Species, the second word in every probiotic name, is more specific. Think Homo sapiens (humans) vs Homo erectus (one of our pre-human ancestors)—same genus, different species.

And the strain is the most granular way to specify probiotics. There are thousands of species and even more strains within each species.

A probiotic name that specifies down to the strain would look like this:

• Lactobacillus rhamnosus HN001
• Bifidobacterium lactis HN019
• Lactobacillus casei ATCC 393

In these examples, the first word is the genus or category (you may also see it abbreviated, as in L. rhamnosus), the second word is the species, and the third set of letters and numbers is the strain. The next time you look at your probiotic supplement, you’ll notice that the specific strain isn’t always specified.

In truth, it’s because that level of specificity doesn’t matter for the end user (that’s you).

What matters is that you ingest a variety of different microbes consistently over time.

Deconstructing the Research: Which Part Matters?

Some general understanding of probiotics can get confusing because of misleading marketing. I’m not assigning blame or malice to marketers—their messaging likely reflects their understanding of the research, or at least what they’re told about the research. But it’s important to decipher what the science says and what we can extrapolate from it. 

For example, you’ve likely seen Lactobacillus acidophilus listed as the main probiotic ingredient in popular yogurt brands. Yogurt has a wide variety of different probiotics in it, but because that specific type of probiotic is recognizable to most people and has been branded as healthy, marketers use it over and over again to sell yogurt. My goal is to broaden your understanding of how to use probiotics without getting bogged down with specific strains because, ultimately, the specific strains don’t matter.

Don’t Miss the Forest for the Trees

When researchers conduct experiments, scientists will usually specify down to specific strains to reduce the total variables in a study. While this is good for the scientific method, it may also lead to mistaken conclusions. The high level of -specificity in the research might lead consumers to believe that only the probiotic strain specified in the study will effectively relieve symptoms. This couldn’t be further from the truth.

For example, if you’re looking for probiotics to help with anxiety, you might find a study on mice that used Lactobacillus helveticus ROO52 [1]. You might also see research that observes the effects of Bifidobacterium infantis 35624 or Bifidobacterium longum R0175 on anxiety [2]. These studies only look at these specific probiotic strains, but that shouldn’t lead you to believe that these three strains are the only probiotics worth taking if you have anxiety.

What’s missing is the fact that probiotics are not pharmaceuticals, and they don’t work like pharmaceuticals, targeting specific pathways or symptoms. There’s no specific “mood-enhancing probiotic.” Rather, all probiotics work at the system level, inching out harmful bacteria over time, restoring a healthy gut lining, and diversifying the microbiota. This functional process leads to gastrointestinal improvement and a host of other benefits probiotics are known for. Probiotics may improve:

• Irritable bowel syndrome (IBS) and Inflammatory bowel disease (IBD – including ulcerative colitis and Crohn’s disease) [3, 4, 5, 6]
• Intestinal imbalances like gut dysbiosis, SIBO, and leaky gut [7, 8, 9, 10]
• Acid reflux [11] 

• Constipation, diarrhea, antibiotic-associated diarrhea, and traveler’s diarrhea [12, 13, 14, 15]
• Infections: vaginal, respiratory tract, urinary tract, and oral pathogens [16, 17, 18, 19]

• Mood and mental health disorders like anxiety, depression, and bipolar disorder [20, 21, 22, 23]  
• Brain fog [24]
• Alzheimer’s disease [25, 26]
• Fibromyalgia [27] 
• Sleep issues like insomnia and poor sleep quality [28, 29]
• Autoimmune diseases like type 1 diabetes, rheumatoid arthritis, and multiple sclerosis (MS) [30, 31, 32, 33, 34]
• Metabolic issues related to SIBO  
• Food sensitivities (dairy, gluten), allergies, and seasonal allergies [35, 36, 37]
• Histamine intolerance 
• Female hormone balance [38, 39, 40]
• Cardiovascular health: blood pressure and cholesterol [41, 42, 43] 
• Thyroid function [44] 
• Skin health: acne, rash, dermatitis, rosacea, and more [45, 46, 47, 48, 49]
• Infant and mom health [50, 51] 

Based on the research supporting the use of a variety of species and strains, I recommend an approach that brings all three categories into every dose. I’ve seen incredible improvements in my clinical patients who have transitioned to what I call a Triple Therapy Probiotic Protocol—taking probiotics from all three categories. By doing this, you’re not only reaping the benefits of each individual strain, you’re also receiving the synergistic effects that I continually see in my clinic.

Simplicity Wins the Race

Since we’re on the topic of debunking, I’ll also use this time to advocate for simplicity over the complex advice that some advocate for. Advice like taking a probiotic with food, at a specific time of day, or rotating your formula every month or two is not based on science. 

Instead of getting caught in the weeds, stick to the simple rules for all behavior change: pay attention and stick to what works. Let’s run through the probiotic fundamentals.

There’s no evidence to suggest that probiotics are more effective if you take them on an empty or full stomach. It doesn’t matter. It only matters that you take them consistently.

There’s no evidence to suggest one time of day is better than any other for taking your probiotic. Rather, you should listen to your body and notice for yourself if you prefer to take them at a specific time, based on your symptoms. And if your body isn’t making any suggestions, then the best time to take them is the time of day that you’ll remember to take them consistently.

There is no evidence to suggest that rotating your formula periodically does anything to improve the efficacy of your probiotics. This applies whether you’re talking about probiotic supplements or probiotic foods like sauerkraut, kombucha, or kimchi. As long as there’s variety in your formula (multi-strain, multi-species, multi-category) and you’re taking a high-quality product without needless filler or common allergens (gluten, lactose, shellfish), then there’s no need to switch it up if it’s working for you. 

Important note: Keep an eye out for prebiotic additives. If you have SIBO, you’ll also want to avoid probiotic formulas that include prebiotics, as those can irritate SIBO. Anything over three grams can be problematic and increase SIBO symptoms. 

In my clinical experience, it can take up to three months of consistent use to see the benefits of probiotics, which may support NOT switching your formulas too often. Both ancestral research and the present scientific evidence show that the gut microbiota benefits from consistent support—daily intake of beneficial bacteria, whether through food or supplements.

Probiotics are Fragile: Debunked

And on the topic of simplicity, the supposed fragility of probiotics is another facet that’s been overcomplicated. What we know about probiotics has changed over time. Change over time with the accumulation of more information occurs across every area of science, which makes scientific understanding a living, breathing thing. It’s important to make room for new scientific discoveries rather than sticking to one way of understanding and falling into the trap of dogmatic thinking. When I was a teenager, doctors thought that giving copious amounts of antibiotics would help pubescent acne. Now we know that doing that causes more harm than good, so the approach has changed.

When probiotics first came to market, we thought that the living microorganisms were delicate and had to be protected from heat and stomach acid, otherwise they would die and become ineffective. We thought they needed to be refrigerated and enteric-coated for safe transport to the gut.

We also thought that probiotics were only effective if they made it all the way to the large intestine to form colonies there (hence the standard unit of measure we still use—CFU: colony-forming units). Not only has the understanding around protecting probiotics shifted, so too have we learned that not all strains and species can form colonies in our digestive tract. It turns out that only the soil-based (Bacillus) varieties are able to form colonies, but all categories remain effective and beneficial, whether they form colonies are not. The unit of measure is a relic of old science, a perfect example of my point.

There’s no evidence to suggest that enteric coating improves probiotic efficacy by protecting them from stomach acid. There’s also no evidence to suggest that probiotics are effective only if they make it all the way to the large intestine. In fact, the small intestine is often the site of leaky gut syndrome and gut dysbiosis like SIBO, and there’s plenty of evidence to support the use of probiotics for SIBO patients [7]. 

And regarding refrigeration, as long as you’re storing your probiotics below 77°F, they’re safe. You don’t need to refrigerate them as a consumer [52]. 

Interestingly, even if they’re exposed to too much heat, they may still be effective. Four clinical trials looking at heat-killed versus live probiotics showed no difference in the effects of probiotics, even when controlling for placebo. The heat-killed remained beneficial for improving IBS symptoms, treating skin allergies, enhancing the immune system, and reducing colds [48, 53, 54, 55].  

Another very surprising study found that heat-killed Lactobacillus was more effective than living Lactobacillus in treating diarrhea [56]. It turns out that good bacteria are good for you, whether they’re dead or alive.

Find Your Minimum Effective Dose

There’s always nuance to every piece of healthcare advice. I’ve suggested the Triple Therapy approach to taking probiotics as the best way to take probiotics. But if you’re particularly sensitive or inflamed, you might find that taking all three categories at once is causing bloating or abdominal pain. If that’s the case, back off and try one at a time. Although rare, people can sometimes experience side effects from taking probiotics, especially if they are at the beginning of their gut health journey.

Side effects may include general mild gastrointestinal symptoms such as [57, 58]:

• Abdominal cramping
• Nausea
• Soft stools
• Gas
• Taste disturbance
• Symptoms of a die-off reaction, such as fatigue, irritability, headache, and flu-like symptoms [57, 58]

A Protocol to Get Started

If the Triple Therapy protocol is causing your body distress, start with one category at a time, roughly every few days. If any probiotic causes a negative reaction lasting longer than five to seven days, stop taking that formula, at least for now, until your immune system calms down and your gut begins to heal.

Here’s a suggested schedule:

1. Take a category 1 (Lactobacillus and Bifidobacterium blend) on Monday, and see how you feel for the next few days. If you don’t feel worse …
2. Take categories 1 and 2 (Saccharomyces boulardii) on Friday. If all goes well …
3. Take all three categories on the following Tuesday (Lacto-Bifido blend, S. boulardii, and soil-based).

If you’re starting with Triple Therapy packets, this schedule won’t work because the packets contain all categories. However, you’re welcome to start smaller than one packet daily by taking one packet every few days or starting with a half dose daily. You may want to eyeball what half a packet is or use a kitchen scale to weigh it out. It’s not important for you to be overly precise.

At full strength, I recommend the potencies below for each category, used consistently over a minimum of two to three months:

• Lactobacillus/bifidobacterium blends: 10 billion CFU
• Saccharomyces boulardii: 10-15 billion CFU
• Soil-based (Bacillus): 2-6 billion CFU

You may use higher dosing—and I have done that in certain circumstances with my patients—but the ideal dose seems to be in the ranges above. Studies showing probiotic effectiveness for health conditions have commonly used around 100 million to 10 billion CFUs, but some have safely used as much as 3.6 trillion CFUs [59].

Most likely, given positive outcomes in studies that gave people very high doses of probiotics, nothing bad is likely to happen if you take up to a few trillion CFUs, as long as the probiotic product is from a reliable manufacturer and has no common allergens in it [60, 61, 62].  

Going into mega-dosing with numbers a lot higher than the recommended protocol might exacerbate your symptoms, and it might also be a waste of money. With my patients, I recommend taking the triple therapy probiotic until they see some improvement in symptoms (usually three to four weeks). I have them stay on for an additional two to three months to hit peak benefit and then cut down to a minimum effective dose.

How to Find a Minimum Effective Dose

Anytime you see a dose range (‘one to two capsules,’ for example), it’s best to start at the minimal dose. After a few days at this dose, see how you feel. If you’re feeling great, stay at that dose. If you still need further improvement, increase to the full dose. This will help you find the minimal dose required, which is always our goal. More is not always better [58]. If you have a die-off reaction (fatigue, irritability, headache, flu-like symptoms), it’s normal and should only last a few days to a week. Sometimes, reducing your dose of probiotics early on can mitigate these symptoms [58].

If you’ve started with a higher dose, you can also experiment with lowering your dose by half to see if you can continue experiencing benefits at a lower dose. Finding your minimum-effective does isn’t an exact science, and it requires you to pay attention over time. Keeping a symptom journal may help you really dial in exactly what you need. If you’ve cut your dose in half but continue to experience the same benefits three or four weeks out, you know your new, smaller dose is sufficient. If your symptoms begin to return, then you’ve cut back too much.

What is the Best Probiotic Strain?

Hopefully, by now, you recognize that this isn’t quite the question you should be asking. Rather, diversity, consistency, and proper dosing will get you where you need to go. As long as you’re using a high-quality probiotic formula free from common allergens and unnecessary fillers, you remember to take it consistently, and the dosing is working for you; you’re doing great.

There’s no reason to look for specific strains or species to match specific symptoms or ailments, as there’s not enough evidence yet to support getting overly particular with specific strains for specific conditions.

All probiotic formulas will benefit your immune health, digestive health, cardiovascular health, and mental health. All probiotic formulas work to balance your gut bacteria, moving the bad bacteria out and the good bacteria in.

Keep it simple and find a routine that you can stick to. Now that we know that probiotics can be stored at room temperature (below 77° F), you might find that taking them out of the refrigerator helps you remember to take them. If that’s you, do it!

If you’d like support in getting started on your gut health journey, reach out to our clinic. We’d love to help.

The Ruscio Institute has developed a range of high-quality formulations to help our patients and audience. If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you.