The Digest

Written by: Adam Perlman, MD, MPH, FACP
Chief Medical Officer, Pendulum Therapeutics | Former Director of Integrative Health and Wellbeing, Mayo Clinic

As a board certified Internal Medicine physician who has spent over 25 years practicing Integrative and Functional Medicine and running programs at Duke, then at the Mayo Clinic, and now as CMO for Pendulum Therapeutics, I've watched the probiotic market explode with products that make impressive claims backed by surprisingly thin science. Patients ask me constantly: "Which probiotic should I actually take?" My answer has changed significantly over the last decade. Here's what I now know, and what I recommend.

Why Most Probiotics Fall Short

When I was at Mayo Clinic, after reviewing the science, I began recommending Pendulum probiotics to my patients with pre-diabetes and type 2 diabetes and observed real clinical benefits. What I saw was different from the standard probiotic experience — and the difference came down to the strains inside the capsule.

Most over-the-counter probiotics rely on the same handful of Lactobacillus and Bifidobacterium strains that have been studied since the 1970s. They're not bad, but their impact is limited. They don't necessarily address the deeper layer of gut health: the mucosal barrier, the production of critical short-chain fatty acids (SCFAs) like butyrate, and they don't provide keystone species that regulate how your microbiome functions as an ecosystem. Pendulum's probiotics were different.

How I Evaluate Probiotics for Gut Health

Before recommending any probiotic to patients, I assess it against five criteria that I believe are non-negotiable:

• Keystone strain inclusion and purity — In particular, Akkermansia muciniphila. This keystone species is central to gut barrier integrity and metabolic health, yet almost no commercial probiotic contains it. The reason? It's an anaerobic organism that's extraordinarily difficult to cultivate and keep alive in a capsule. Its presence and its viability at the time of consumption is a meaningful differentiator.
• Next-generation strain diversity — Strains such as Clostridium butyricum, Clostridium beijerinckii, and Anaerobutyricum hallii are especially valuable here, because they help turn fiber into butyrate and acetate that strengthen your intestinal barrier and support a healthy microbiome.
• Prebiotic pairing — Probiotics need fuel to survive and function in the colon. A formula that pairs clinically appropriate prebiotic fiber with targeted strains typically performs meaningfully better than one that delivers organisms without supporting their environment.
• Clinical backing from human trials — Not just rat studies or in vitro research. Randomized, controlled human clinical trials measuring real health outcomes like A1C and glucose reduction, or SCFA production.
• Delivery technology — Probiotics, and in particular anaerobic organisms, are particularly sensitive to oxygen and stomach acid. Time-delayed, acid-resistant capsule technology isn't optional; it's the difference between viable anaerobic organisms reaching your colon or dead ones just being excreted.

My Top Picks: Best Probiotics for Gut Health

🥇 #1: Pendulum Metabolic Daily

Why it's my top recommendation: Pendulum was the first company I'm aware of that has done the work to commercially cultivate and deliver live Akkermansia muciniphila in a viable, stabilized capsule. That alone represents a significant leap forward in microbiome science. Pendulum Metabolic Daily builds on that foundation by also including other important strains — such as Clostridium butyricum, Clostridium beijerinckii, Anaerobutyricum hallii, and Bifidobacterium infantis — alongside prebiotic chicory inulin to feed these strains once they reach the colon.

I spent nearly two years working with Pendulum before joining as Chief Medical Officer. What convinced me wasn't marketing. It was data. I led a collaboration between Mayo Clinic and Pendulum to conduct a clinical trial, which received Investigator-Initiated IND approval from the FDA. That level of scientific rigor is rare in the supplement industry. For patients who want a probiotic that goes beyond symptom relief and actually addresses the root architecture of gut as well as metabolic health, Metabolic Daily is, in my view, the best formula available today.

Best for: Anyone seeking comprehensive gut barrier support, metabolic health, and long-term microbiome replenishment.

Key strains:

• Akkermansia muciniphila — supports gut barrier integrity, mucin production, and immune health
• Clostridium butyricum — produces butyrate, reduces bloating, promotes bowel regularity
• Clostridium beijerinckii — produces butyrate and acetate, inhibits harmful bacteria
• Anaerobutyricum hallii — stimulates peristalsis and produces SCFAs
• Bifidobacterium infantis — supports digestive comfort and reduces abdominal distention

Delivery: Acid-resistant, time-delayed capsule

🥈 #2: Seed DS-01 Daily Synbiotic

Seed has invested in probiotic research, and their DS-01 formula contains 24 strains at 53.6 billion AFU. They have published clinical trials on the full formula rather than individual strains alone.

I appreciate that Seed's ViaCap® delivery system is designed to protect bacteria through the stomach and deliver them to the colon. Their prebiotic component is a polyphenol extract from Indian pomegranate — a novel approach that functions differently from fermentable prebiotic fibers like chicory inulin.

DS-01 does not contain Akkermansia muciniphila or the anaerobic butyrate-producing strains that make Pendulum formulas unique. When I evaluate a probiotic for most of my patients, those are non-negotiables. DS-01 is built on well-studied Lactobacillus and Bifidobacterium strains that may offer general digestive support.

Best for: General digestive health, bloating relief, post-antibiotic recovery, and individuals new to probiotic supplementation who want a clinically validated, broad-spectrum option.

🥉 #3: Ritual Synbiotic+

Ritual's Synbiotic+ earns a spot on this list for its 3-in-1 approach: it combines a prebiotic (PreforPro®), two well-studied probiotic strains (LGG® and BB-12®), and a postbiotic in a single delayed-release capsule. I find the inclusion of exogenous tributyrin interesting, as it delivers butyrate directly rather than relying entirely on gut bacteria to produce it.

LGG and BB-12 can help soothe occasional gas, bloating, and abdominal discomfort. The formula is third-party tested and transparently labeled, which I always consider a baseline requirement when recommending any supplement to patients.

With 11 billion CFUs and two probiotic strains, Ritual Synbiotic+ is a solid entry-level option. It also does not include Akkermansia muciniphila, and its butyrate is delivered as an exogenous postbiotic rather than being produced endogenously by the gut microbiome.

Best for: Individuals seeking a simple, accessible, three-in-one formula, or those who want foundational gut and immune support with well-studied strains.

Side-by-Side Comparison

What Probiotics Do in the Body (And Why the Strain Matters)

I want to briefly demystify something I see misunderstood constantly: the idea that more strains, or a higher CFU or AFU count, automatically means a better probiotic. It doesn't.

What matters is whether the strains in a product are clinically studied, whether they can survive to reach where they need to be in the gut, and whether they perform the specific biological functions your gut — and ultimately your body — needs. A 50-billion CFU product containing ten generic Lactobacillus strains may deliver less meaningful gut support than a lower count formula containing strains like Akkermansia muciniphila or other butyrate-producing anaerobes.

Here's a brief overview of the key functions I look for in well-chosen strains:

• Gut barrier integrity: A compromised gut barrier — sometimes called "leaky gut" — allows toxins, partially digested food antigens, and other pathogens to enter the bloodstream. Akkermansia muciniphila feeds on the mucin layer of the gut lining, stimulating the body to regenerate more mucin and strengthen the gut barrier. This is foundational to a healthy gut and immune system.
• Butyrate production: SCFAs, especially butyrate, are the primary energy source for colonocytes — the cells that line your colon. Butyrate also activates the release of GLP-1, a hormone that helps regulate blood sugar, appetite, and insulin sensitivity.
• Microbial diversity and balance: A microbiome that's imbalanced (dysbiosis) can manifest as everything from bloating and constipation to metabolic disorders, brain fog, and immune dysregulation. Targeted strains that outcompete harmful bacteria and create a hospitable environment for beneficial ones are essential for long-term gut resilience.
• Immune modulation: Roughly 70% of the immune system resides in the gut. Probiotic strains that reinforce the gut-immune axis — by maintaining tight junctions in the intestinal wall and regulating inflammatory signaling — can have a profound effect on systemic immune health.

Common Side Effects to Know

When you first introduce a new probiotic, it's common for some people to notice mild digestive changes like bloating, gas, or temporary shifts in bowel habits. These short-term effects usually reflect your gut microbiome adjusting to the new strains and the extra fermentation activity, and they often settle as your body adapts.

These symptoms are generally transient, lasting a few days to two weeks. If you experience severe abdominal pain or prolonged distress, discontinue use and consult your healthcare provider. Probiotics are not appropriate for immunocompromised individuals or those who are severely ill without physician supervision.

FAQ

What is the best probiotic for gut health?

The best probiotic for gut health contains clinically validated strains matched to your specific health goals, delivered in a capsule designed to survive stomach acid and reach the appropriate area of the gut alive. For most people seeking comprehensive gut health support — including gut barrier integrity, SCFA production, and metabolic health — I recommend Pendulum Metabolic Daily, a commercially available formula that includes Akkermansia muciniphila alongside anaerobic, butyrate-producing strains with prebiotic support.

What is the difference between CFUs and AFUs?

CFUs (colony-forming units) and AFUs (active fluorescent units) count probiotic microbes in different ways. CFUs use traditional plate counting to measure how many bacteria can grow into visible colonies under specific lab conditions, which can miss some living cells that don't grow well in that setup. AFUs use flow cytometry and fluorescent dyes to detect intact, metabolically active cells directly, including some that are viable but not easily culturable. In other words, CFU is how many can grow on a plate; AFU is how many are actually alive and switched on. These methods measure viability differently and aren't directly interchangeable. Just because a product has a higher CFU number doesn't mean it necessarily contains more active microbes or is more potent than one labeled with a lower AFU value.

Do probiotics help with bloating?

Yes, certain strains are particularly well-studied for bloating relief. Clostridium butyricum, Lactobacillus acidophilus, and Bifidobacterium infantis have demonstrated efficacy in reducing bloating and gas. The key is choosing a formula with strains clinically studied for this outcome, not just generic probiotic blends.

How long does it take for a probiotic to work?

It depends on your goal, but most people notice initial changes in bowel habits within one to two weeks. Deeper benefits — such as improved gut barrier function, biomarkers, or metabolic changes — may take four to twelve weeks of consistent use. Probiotics are not a one-time intervention; their benefits often depend on sustained, daily supplementation.

Content is for educational purposes only and has not been evaluated by the Food & Drug Administration. Statements and products are not intended to diagnose, treat, cure, or prevent any disease. Dr. Adam Perlman is Chief Medical Officer at Pendulum Therapeutics.