What Are the Side Effects of L. Reuteri?

Lactobacillus reuteri (now formally reclassified as Limosilactobacillus reuteri) is one of the most extensively studied probiotic species, and for most healthy people taking standard doses, genuine side effects are mild and uncommon. In fact, several meta-analyses have found that people taking L. reuteri reported fewer digestive complaints than those on placebo, not more. The real concerns show up at the edges: in people who are critically ill, who have short bowel syndrome, who are prone to histamine reactions, or who have autoimmune conditions. Those situations deserve a closer look.

Mild Digestive Symptoms Are the Most Common Complaint

The side effects most frequently mentioned in clinical trials of L. reuteri are the same ones you hear about with nearly any probiotic: gas, mild bloating, and occasional loose stools. These tend to appear during the first few days of supplementation and usually fade as the gut adjusts. In controlled studies, however, these symptoms often show up at similar rates in the placebo group, making it hard to blame the probiotic itself.

A large meta-analysis pooling data from randomized controlled trials of L. reuteri used alongside standard antibiotic treatment for H. pylori infection found something that surprises most people: the group taking L. reuteri actually had a roughly 28-30% lower rate of adverse events compared to placebo.¹ A separate randomized trial using an inactivated (postbiotic) form of L. reuteri DSM 17648 in adults with functional dyspepsia similarly reported that digestive side effects were lower in the treatment group, with no serious adverse events recorded.² That context matters: when someone reads alarming lists of probiotic side effects online, the clinical trial data often tells a more reassuring story for typical, healthy users.

Histamine Production and Sensitivity

This is where things get more specific to L. reuteri and less about probiotics in general. Certain strains of L. reuteri, particularly L. reuteri 6475 (also known as ATCC PTA 6475), carry a gene cluster that enables them to convert the amino acid L-histidine into histamine. Researchers have confirmed that the histidine decarboxylase gene (hdcA) and a related histamine transporter are directly involved in this process.³

In the body, that bacterial histamine actually appears to do something useful: it suppresses the pro-inflammatory molecule TNF, which is why L. reuteri 6475 has been studied for its anti-inflammatory properties. But histamine is also the molecule behind allergy symptoms, headaches, flushing, and digestive distress in people who are histamine-intolerant or who have mast cell activation issues. If you already react badly to aged cheeses, fermented foods, or wine, a histamine-producing probiotic strain could make things worse. Not all L. reuteri strains carry this gene cluster, so the strain designation on the label matters. DSM 17938, the most widely sold L. reuteri strain for infant colic and general gut health, is a different strain from 6475 and is not typically flagged for histamine production.

Safety in Infants and Children

L. reuteri DSM 17938 is probably the single most studied probiotic strain for infant colic, and its pediatric safety record is strong. A double-blind, placebo-controlled trial in colicky infants found no severe adverse events in the L. reuteri group. Mild adverse events occurred at similar rates in both groups, and the difference was not statistically significant.⁴ A meta-analysis of randomized controlled trials on L. reuteri for infantile colic confirmed this broader pattern: the strain did not affect infant weight, length, or head circumference and was not associated with serious adverse events.⁵

A clinical review of L. reuteri DSM 17938 at a standard pediatric dose of 100 million colony-forming units per day concluded that it has the most scientific support of any probiotic for infant colic and has not shown significant side effects.⁶ Trials in children with acute diarrhea, using higher doses of 400 million CFU per day for a week, also reported no side effects.⁷ For parents considering L. reuteri for a colicky baby, the evidence is about as reassuring as probiotic evidence gets. That said, premature infants and babies with compromised immune systems are a different conversation, and the risks described below for critically ill patients apply in scaled-down form to vulnerable neonates as well.

Bloodstream Infections in Critically Ill Patients

The most serious documented risk of any probiotic, L. reuteri included, involves people who are already severely sick. A study of over 23,000 ICU patients who received probiotics found that 86 of them developed bloodstream infections caused by organisms contained in the probiotic products they were given. That works out to about 0.37% of the ICU patients studied, and these probiotic-associated bloodstream infections were linked to increased mortality.⁸

The mechanism is straightforward: patients in intensive care often have central venous catheters and compromised gut barriers, which means live bacteria that would normally stay safely inside the intestine can enter the bloodstream. This risk is not unique to L. reuteri and applies to many probiotic species, but it is a stark reminder that “safe for healthy people” and “safe for everyone” are not the same statement. If you are immunocompromised, receiving chemotherapy, critically ill, or have a central line in place, live probiotics of any kind should only be used under direct medical supervision.

D-Lactic Acidosis in Short Bowel Syndrome

D-lactic acidosis is a rare but serious metabolic condition that shows up almost exclusively in people with short bowel syndrome. When a large portion of the small intestine has been removed or bypassed, carbohydrates that would normally be absorbed instead pass into the colon, where bacteria ferment them. Some bacteria, including certain lactobacilli, produce D-lactic acid as a byproduct of that fermentation. If D-lactate builds up faster than the body can clear it, the result is acidosis that can cause confusion, slurred speech, and coordination problems resembling intoxication.⁹

For most people, this is not a concern. The healthy small intestine absorbs carbohydrates long before they reach the colon in quantities that would matter. But for the small number of people living with short bowel syndrome, adding a D-lactate-producing bacterium to the gut on purpose is worth discussing with a gastroenterologist before starting any Lactobacillus supplement.

Autoimmune Risk in Susceptible Hosts

Most research on L. reuteri highlights its anti-inflammatory and immune-modulating effects, which is why it is studied for conditions ranging from colic to eczema. But the immune system is not a dial that simply goes up or down. A review examining Lactobacillus species in the context of autoimmune disease found that while certain strains clearly provide immune benefits, others can behave as pathobionts in hosts that are already predisposed to autoimmunity. In animal models and preclinical settings, some strains have been shown to cross a dysfunctional gut barrier, reach internal organs like the spleen and liver, and promote inflammatory responses that worsen autoimmune disease.¹⁰

The evidence here is largely preclinical, meaning it comes from lab and animal studies rather than from human clinical trials. It would be wrong to conclude that L. reuteri causes autoimmune disease in people. But it would also be careless to ignore the pattern. If you have an active autoimmune condition, particularly one involving the gut like inflammatory bowel disease or celiac disease, the decision to add a probiotic is worth a conversation with your doctor rather than a solo trip to the supplement aisle. The strain, the dose, and the state of your gut barrier all matter in ways that a generic “probiotics are good for you” message does not capture.

Why the Strain on the Label Matters

One of the most important things to understand about L. reuteri side effects is that “L. reuteri” is not one organism with one set of behaviors. Different strains can have meaningfully different properties, including different safety profiles. The history of L. reuteri ATCC 55730 illustrates this well. This was the original commercially used strain, widely sold and studied for years. Then researchers discovered it harbored two plasmids carrying antibiotic resistance genes: one for tetracycline resistance and one for lincosamide resistance. A daughter strain, DSM 17938, was deliberately derived from ATCC 55730 by curing those two plasmids, and subsequent testing confirmed that the new strain lost the resistance traits while retaining its probiotic properties.¹¹

The concern with antibiotic resistance genes in probiotics is not that the probiotic itself will infect you with a resistant bug. Rather, bacteria can swap genetic material with each other in the gut. If a probiotic carries a resistance gene on a mobile piece of DNA, that gene could theoretically transfer to a pathogenic bacterium, making the pathogen harder to treat with antibiotics. Research has confirmed that L. reuteri and related species can potentially serve as reservoirs for antibiotic resistance genes that might be transferred to other bacteria in the gut or through the food chain.¹²

DSM 17938 addressed this for one commercial strain, but the broader point stands: not all L. reuteri products on the market use strains that have been screened this carefully. If a supplement label simply says “L. reuteri” without a specific strain designation, you have less information about what you are actually taking. The strain number (like DSM 17938, ATCC PTA 6475, or DSM 17648) is the best indicator that the product has been through controlled studies and that safety data exist for that specific organism.

What Happens When You Stop Taking It

A question that often follows concerns about side effects is: if something does go wrong, how long will the effects last after you stop? The answer for L. reuteri is reassuring. Unlike some gut bacteria that take up permanent residence, L. reuteri does not colonize durably in most people. A study tracking L. reuteri DSM 17938 in healthy volunteers found that gut counts rose during supplementation but dropped sharply within a week of stopping. By two weeks after the last dose, only about two out of nine volunteers in each group still had detectable L. reuteri.¹³

An interesting secondary finding from this research was that taking L. reuteri every other day achieved roughly the same colonization level as daily supplementation, and both schedules saw the same rapid washout once dosing ended.¹⁴ For people experiencing mild side effects, this means that stopping the supplement should resolve any gut-related discomfort within days. It also means that any benefits require ongoing use, since the bacteria do not stick around on their own.

Drug and Supplement Interactions

L. reuteri is a living organism that resides in the gut, so it interacts with the same environment that your medications pass through. The most straightforward interaction is with antibiotics: if you are taking an antibiotic orally, it will likely kill off a good portion of the L. reuteri you are supplementing, reducing or eliminating any benefit. Some clinicians recommend spacing probiotic doses a few hours away from antibiotic doses to minimize this, though the evidence on how much this helps is mixed. In the H. pylori eradication trials where L. reuteri was used alongside antibiotics, it still showed benefits, but those protocols were specifically designed around the timing.

Immunosuppressive drugs deserve special attention. If you are taking medications that deliberately suppress your immune system, such as after an organ transplant or for an autoimmune condition, live probiotics introduce organisms that a dampened immune system may not handle normally. The bloodstream infection risk discussed earlier applies most acutely here. Antifungal medications do not typically interact with L. reuteri since it is a bacterium, not a fungus, but proton pump inhibitors and other acid-suppressing drugs can change the gut pH in ways that alter where and how effectively probiotics survive. These interactions are generally mild and do not produce dangerous side effects, but they can affect whether the supplement does what you are hoping it will do.

Comparing L. Reuteri to Other Common Probiotics

In the broader landscape of probiotic supplements, L. reuteri has one of the cleaner safety records, partly because DSM 17938 has been put through an unusually high number of controlled trials in vulnerable populations like newborns. Many popular probiotic species, including various Lactobacillus and Bifidobacterium strains, share the same profile of mild, transient digestive symptoms. The ICU bloodstream infection risk also applies broadly across probiotic species, not just to L. reuteri. Where L. reuteri stands out is in the histamine question: not all probiotic species produce histamine, so people with histamine sensitivity may tolerate a Bifidobacterium-based product or a different Lactobacillus species better than a histamine-producing L. reuteri strain like 6475.

The flip side is that the histamine production by L. reuteri 6475 appears to be part of how it exerts its anti-inflammatory effects. Stripping that property away would likely reduce its therapeutic value for the conditions it is studied for. This is a recurring theme in probiotic research: the same biological activity that makes a strain useful can be the one that causes problems in the wrong host. There is no universal “best probiotic” any more than there is a universal “best medication,” and matching the strain to the person is more important than chasing the highest CFU count or the longest ingredient list.