What Probiotic Should I Take With Amoxicillin?

Lactobacillus rhamnosus GG (often labeled as LGG) has the strongest evidence for preventing diarrhea during amoxicillin treatment, with one systematic review finding it cut the risk of antibiotic-associated diarrhea by about 70% compared to placebo. Saccharomyces boulardii, a probiotic yeast, is the other frequently recommended option, though its track record with amoxicillin specifically is more uneven than its reputation suggests. The honest picture is that strain choice matters far more than brand name, and several popular products on pharmacy shelves contain strains with little or no evidence behind them for this particular use.

What Amoxicillin Does to Your Gut Bacteria

Amoxicillin is a broad-spectrum penicillin, which means it does not limit its killing to the bacteria causing your infection. It sweeps through the gut and reduces the diversity and richness of your intestinal microbiome within days of starting treatment. In a study tracking microbiome changes during amoxicillin courses, researchers observed significant drops in bacterial diversity, richness, and evenness, with shifts in the major bacterial groups that dominate a healthy gut.¹ Animal studies confirm the picture: oral amoxicillin substantially lowers bacterial diversity in the large intestine and disrupts both the composition and metabolic activity of the resident microbiome.²

One of the more specific casualties is the group of bacteria that produce short-chain fatty acids, which are compounds that feed the cells lining your colon and help keep inflammation in check. A placebo-controlled trial in healthy adults found that these beneficial species dropped significantly during amoxicillin treatment.³ The good news from that same study: most of the microbiome bounced back within about nine months after treatment ended. But in the short term, the disruption is real, and that gap is where diarrhea, cramping, and other gut symptoms tend to show up.

Lactobacillus Rhamnosus GG Has the Best Data

If you want a single answer to the title question, it is LGG. A systematic review evaluating multiple probiotic strains and formulations for antibiotic-associated diarrhea found that LGG was the most protective single strain, with a relative risk of 0.30 compared to placebo. In plain terms, people taking LGG were about 70% less likely to develop diarrhea than those taking a placebo.⁴ That is a large effect by the standards of supplement research, where most interventions show modest benefits at best.

LGG also has specific evidence with amoxicillin-containing regimens. A review focused on children receiving amoxicillin or amoxicillin-clavulanate confirmed that LGG can survive alongside these antibiotics and supported its recommendation for use during treatment.⁵ This matters because not every probiotic bacterium can actually stay alive when amoxicillin is circulating in the gut. LGG appears to tolerate the antibiotic environment well enough to exert its effects.

You will find LGG sold under several brand names, most prominently Culturelle. The strain designation “GG” is what to look for on the label, not just the species name Lactobacillus rhamnosus, since different strains of the same species can behave very differently.

Saccharomyces Boulardii Has a More Complicated Story

S. boulardii is the other probiotic you will see recommended alongside antibiotics, and it has one inherent advantage: it is a yeast, not a bacterium. Because antibiotics like amoxicillin target bacterial cells, S. boulardii is naturally unaffected by the drug. It will not be killed off the way a bacterial probiotic might be. This makes it an appealing choice in theory, and it is the reason many pharmacists suggest it.

In practice, the evidence is more mixed than the marketing implies. A trial specifically testing S. boulardii at 500 mg per day alongside amoxicillin in adult outpatients found that it did not prevent diarrhea.⁶ Another randomized trial in elderly hospitalized patients receiving various antibiotics found that S. boulardii performed no better than placebo, with diarrhea rates of about 15% in the probiotic group versus 13% in the placebo group.⁷

That said, S. boulardii has performed well in other contexts. A randomized trial testing it alongside a vonoprazan-amoxicillin regimen for H. pylori infection found that adding S. boulardii cut overall adverse events from about 21% to 5%, with abdominal pain dropping from 9% to zero.⁸ The difference may come down to the specific treatment context, the dose used, or the population studied. S. boulardii is not useless, but if your main concern is preventing loose stools during a standard amoxicillin course, LGG has a more consistent record for that specific outcome.

Combining LGG and S. Boulardii

Given that one is a bacterium and the other is a yeast, some researchers have explored whether taking both together might be better than either alone. An in vitro study simulating human gut conditions found that combined supplementation of LGG and S. boulardii had a stimulating effect on the most abundant beneficial bacterial groups during amoxicillin-clavulanate exposure.⁹ That is promising, though the authors themselves noted that confirmatory human trials are still needed.

As for whether multi-strain products are inherently better than single-strain ones, a systematic review found that in most cases they were not. The choice of strain mattered far more than the number of strains in the bottle. In some specific conditions, a particular combination outperformed a single strain, but in most comparisons, single strains performed equivalently to mixtures.¹⁰ The takeaway: a product listing 15 different strains on the label is not automatically superior to one containing a single well-studied strain.

Preventing C. difficile During Amoxicillin Treatment

Beyond ordinary diarrhea, one of the more serious risks of any antibiotic course is a C. difficile infection. This bacterium can flourish when antibiotics clear away its competition, and the resulting illness ranges from mild diarrhea to life-threatening colitis. A meta-analysis pooling 21 randomized trials found that four probiotics significantly improved primary prevention of C. difficile infection: S. boulardii, Lactobacillus casei DN114001, a mixture of L. acidophilus and Bifidobacterium bifidum, and a mixture of L. acidophilus, L. casei, and L. rhamnosus.¹¹ A separate review echoed that probiotics showed promising effects in preventing C. difficile-associated diarrhea and were generally safe and well-tolerated.¹²

This is one area where S. boulardii’s evidence is stronger than its evidence for preventing garden-variety antibiotic diarrhea. If your risk of C. difficile is elevated, whether because of age, hospitalization, or a history of prior C. difficile episodes, S. boulardii is specifically worth discussing with your doctor.

Dosing and Timing

Most of the positive trials used probiotic doses of at least 5 to 10 billion colony-forming units per day. For LGG, typical studied doses fall in the range of 10 to 20 billion CFU daily. For S. boulardii, 250 to 500 mg per day (which corresponds to roughly 5 to 10 billion CFU depending on the product) is the common dose in clinical trials.

Timing relative to your amoxicillin dose matters. The standard advice is to take the probiotic at least two hours apart from the antibiotic. Since amoxicillin is usually taken two or three times per day, a practical approach is to take the probiotic midway between antibiotic doses or with a meal that falls in that gap. Start the probiotic on the same day you begin amoxicillin and continue for at least a week after completing the antibiotic course. Much of the microbiome disruption persists for days to weeks after the last antibiotic dose, so stopping the probiotic the same day you stop amoxicillin means you are withdrawing support during one of the most vulnerable windows.

What About Children?

Amoxicillin is one of the most commonly prescribed antibiotics in pediatrics, used for ear infections, strep throat, and respiratory infections. Diarrhea caused by amoxicillin or amoxicillin-clavulanate is common in children, and the disruption often hits bifidobacteria especially hard.¹³

A large Cochrane-style review of 33 randomized trials involving over 6,000 children found that probiotics cut the risk of antibiotic-associated diarrhea roughly in half, from about 19% in control groups to about 8% in probiotic groups. The most effective results came from specific strains given at a daily dose of at least 5 billion CFU.¹⁴ LGG and S. boulardii are the two strains with the broadest evidence base in children, consistent with the adult data.

A more recent trial tested Bifidobacterium breve PRL2020 specifically in children taking amoxicillin or amoxicillin-clavulanate and found that the probiotic group had significantly fewer diarrhea episodes, less abdominal pain, and fewer daily bowel movements compared to controls. Diarrhea episodes were reported in about 6% of the probiotic group versus roughly 21% of the control group.¹⁵ This strain is newer to the market and less widely available than LGG, but it represents a growing body of evidence that Bifidobacterium species can be a good fit for pediatric antibiotic support, particularly since bifidobacteria are the bacterial group most depleted by amoxicillin in young guts.

Who Should Not Take Probiotics

Probiotics are safe for the vast majority of people taking a standard amoxicillin course. The exceptions are narrow but important. Case reports and reviews have documented infections, including bloodstream infections, endocarditis, liver abscesses, and fungemia, caused by probiotic strains in high-risk patients.¹⁶ The affected individuals are almost always severely immunocompromised, critically ill, or have compromised gut-barrier integrity.

S. boulardii carries a specific warning: because it is a living yeast, it can cause fungemia (yeast in the bloodstream) in vulnerable patients. The CDC’s Emerging Infectious Diseases journal reported cases associated with S. boulardii use and noted that it is not recommended for patients with indwelling central venous catheters, those who are immunocompromised, or those who are critically ill. The authors added that patients whose gastrointestinal tract integrity may be compromised should also use it cautiously.¹⁷

LGG carries a parallel concern. A case report documented recurrent Lactobacillus bacteremia in an immunocompromised patient with a history of probiotic use, adding to a growing number of similar reports. The authors concluded that caution should be taken when using probiotics, including Lactobacillus-based ones, in immunocompromised populations until more safety data are available.¹⁸ If you are on immunosuppressive medications, undergoing chemotherapy, have an organ transplant, or have HIV with a very low CD4 count, talk to your doctor before starting any probiotic.

The Product Quality Problem

Even if you choose the right strain, you are relying on the product actually containing what the label says. This is a real concern. An analysis of 25 commercial probiotic products found that only about a quarter of those listing specific viable organism counts actually met or exceeded their label claims. A third of the products that named specific organisms had at least one species misspelled on the label, which does not inspire confidence in manufacturing rigor.¹⁹ A more recent analysis found that nearly half of the commercial probiotics tested had CFU counts below what the label stated, with the worst offenders falling more than 30-fold short. Products with more than three strains were more likely to show discrepancies between what was labeled and what DNA analysis actually found inside.²⁰

In the United States, probiotics are regulated as dietary supplements, which means they do not undergo the same premarket testing as pharmaceuticals. A few practical tips for navigating this:

Look for the strain: The label should name the specific strain (e.g., Lactobacillus rhamnosus GG), not just the species. If it just says “Lactobacillus blend,” you have no way to know whether the strains inside have any evidence behind them.
Check for third-party testing: Products verified by organizations like USP, NSF, or ConsumerLab have at least been checked against their label claims.
CFU guarantees at expiration: Some labels list CFU at the time of manufacture, which is less useful. Look for products that guarantee a specific CFU count through the expiration date.
Storage requirements: Some probiotics need refrigeration to maintain viability. If a product requires cold storage, check that it was handled properly before it reached you.

Fermented Foods Are Not a Reliable Substitute

Yogurt, kefir, sauerkraut, and kimchi all contain live microorganisms, which raises an obvious question: can you just eat more of these instead of buying a supplement? The short answer is that fermented foods are generally good for your gut, but they are not a dependable replacement for a studied probiotic strain at a therapeutic dose. The strains in commercial yogurt and kefir are not usually the ones with clinical trial evidence for antibiotic-associated diarrhea. A randomized trial in children tested whether kefir could prevent antibiotic-associated diarrhea and found no difference between the kefir group and the placebo group, with diarrhea rates of about 18% and 22% respectively.²¹ Eating yogurt or kefir during your amoxicillin course will not hurt, but do not count on it as your primary protection.

Fiber as a Complementary Strategy

One of the more interesting newer findings is that dietary fiber may independently protect the gut microbiome during antibiotic treatment. A study published in Nature Communications found that fiber supplementation significantly reduced the impact of antibiotic treatment on microbiome composition and function. The mechanism appears to involve keeping the chemical environment in the gut favorable for the survival of beneficial anaerobic bacteria, essentially shielding them from some of the collateral damage antibiotics cause.²² This was demonstrated in an animal model, so we cannot put hard numbers on the benefit in humans yet, but it aligns with what we know about fiber’s role in feeding the short-chain fatty acid producers that amoxicillin tends to deplete. Adding extra vegetables, legumes, and whole grains to your diet during an antibiotic course is a low-risk move that likely helps and certainly does not hurt.

Antibiotic Resistance Transfer

A concern that rarely comes up in pharmacy-counter conversations but is worth knowing about: probiotic bacteria can, in theory, carry antibiotic resistance genes and transfer them to other microbes in the gut. A critical review noted that most consumers focus on the functional benefits of probiotics while overlooking potential risks, including the possibility that probiotic strains could pass resistance genes to pathogenic bacteria.²³ In practice, this risk has not been shown to cause clinical harm in otherwise healthy people taking short probiotic courses. But it is one reason that the “more strains, more is better” philosophy is worth questioning. Taking a targeted, evidence-based strain at an appropriate dose for a defined period is a more prudent approach than loading up on every probiotic product on the shelf and continuing indefinitely.