Probiotics: Side Effects, Dangers and Contraindications, According to Studies

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Probiomix

Three complementary active ingredients in two capsules per day : 600 mg of Fibregum acacia fiber, 2 billion spores of LactoSpore (Heyndrickxia coagulans MTCC 5856), and 50 mg of Plenibiotic, a postbiotic of heat-inactivated Lacticaseibacillus paracasei 327. To be taken preferably in the morning on an empty stomach or before a meal, in a 1 to 3 month course. Vegan, gluten-free, lactose-free, sugar-free, and low FODMAP.

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A probiotic is, according to the definition adopted by Cochrane reviews, a preparation of living microorganisms that, in sufficient quantity, provide a health benefit: lactobacilli, bifidobacteria, Saccharomyces boulardii yeast, spore-forming bacteria of the Bacillus genus, or mixtures. Added to these are postbiotics, inactivated microorganisms that are no longer alive at all.

There is therefore no single safety profile. A reference review published in Clinical Infectious Diseases identifies five families of theoretical risks described in clinical cases, trials or experimental models: systemic infections, deleterious metabolic activities, excessive immune stimulation in predisposed individuals, gene transfer and digestive effects. The authors emphasize a long history of problem-free use, while noting that the frequency and severity of adverse effects remain poorly measured.

This reservation is not merely theoretical. A systematic review of 384 randomized trials published between 2015 and 2018 on probiotics, prebiotics and synbiotics showed that 28% reported no data on adverse effects, 37% did not publish safety results and 80% did not provide the number of serious effects per group. The reassuring figures that follow are real, but they are based on the portion of trials that properly measured them.

Cochrane meta-analyses provide the most robust data. In children treated with antibiotics, the 2019 review included 33 trials and 6,352 participants. The most common adverse effects: rash, nausea, gas, flatulence, bloating and constipation.

In adults and children treated with antibiotics, the Cochrane review on prevention of Clostridioides difficile diarrhea analyzed adverse effects in 32 trials and 8,305 participants: their risk was even 17% lower with probiotics (relative risk 0.83, very low certainty). Most frequent complaints in both groups: cramps, nausea, fever, loose stools, flatulence, altered taste. The authors consider short-term use safe outside of immunosuppression or severe frailty.

In irritable bowel syndrome, a meta-analysis of 82 trials and 10,332 patients published in 2023 points in the same direction: in the 55 trials that counted adverse effects, involving over 7,000 patients, the risk of experiencing one was not significantly higher with probiotics.

These syntheses do not measure the timing of symptoms: nothing confirms that gas concentrates in the first few days. In practice, monitor your tolerance for one to two weeks and stop if discomfort persists or worsens. Our guide on bloating reviews their other causes.

The fibers often associated with probiotics are fermented by the colon microbiota. A meta-analysis of 16 randomized trials in 1,251 constipated adults shows the benefit of fiber, with 66% responders versus 41% in controls, especially for psyllium and pectin at doses above 10 g per day; stool frequency only improved after 4 weeks. It also measures the downside: more pronounced flatulence with fiber, with an effect size of 0.80, which corresponds to a substantial effect.

In a 12-week primary care trial of 275 patients with irritable bowel syndrome, 10 g per day of psyllium increased the proportion of relieved patients, 57% versus 35% on placebo in the first month, and reduced symptom severity by 90 points versus 49. Wheat bran, an insoluble fiber, led to the most early withdrawals, mainly because symptoms worsened.

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Organic blonde psyllium

100% organic blonde psyllium (Plantago ovata), in powder form, with no other ingredient. 5 to 10 g per day in a large glass of water, to be drunk immediately after mixing.

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In the irritable bowel trial, patients took 10 g of psyllium per day for 12 weeks; our Organic blonde psyllium is taken at 5 to 10 g per day, in a large glass of water, at least 2 hours away from any medication, and is not recommended before age 12. The Probiomix, meanwhile, provides 600 mg of Fibregum acacia fiber per day, a low amount compared to the fiber doses in these trials, in a low-FODMAP formula; no study identified via PubMed measures the tolerance of this specific combination.

Bacteremia is the presence of bacteria in the blood. For lactobacilli, population data are reassuring. In Finland, where the Lacticaseibacillus rhamnosus GG strain has been marketed since 1990 and is widely consumed, lactobacilli represented only 0.02% of all blood cultures, with no upward trend despite the rise of probiotics. The incidence was 0.3 cases per 100,000 inhabitants per year between 1995 and 2000. This observational study does not prove the absence of individual risk.

The picture changes in the most fragile patients. In Boston, a team analyzed five and a half years of pediatric and neonatal intensive care hospitalizations, involving 22,174 patients.

Disturbing point: the 6 affected patients had neither severe immunosuppression nor intestinal wall damage, and comparison with 16 controls revealed no distinguishing factors. At-risk patients are therefore difficult to identify.

The randomized PROSPECT trial, conducted in 44 intensive care units, confirmed this signal. In 2,650 adults on mechanical ventilation, 10 billion units of L. rhamnosus GG twice daily did not reduce ventilator-associated pneumonia, 21.9% versus 21.3% under placebo. On the other hand, 15 patients on probiotic (1.1%) had L. rhamnosus isolated from a normally sterile site or as the principal organism from a sample, compared to 1 on placebo (0.1%).

Lactobacilli sometimes cause endocarditis, an infection of the heart valves. A review identified 17, 15, and 16 published cases of lactobacillus infections in 2019, 2020, and 2021, including endocarditis, bacteremia, and other infections combined, whether or not related to a probiotic, particularly in people with diabetes or immunosuppression, with a prosthetic valve, dental procedures, or cavities. A review of lactobacillus endocarditis cases published since 1992 lists valve disease, dental or invasive procedures, and probiotic use as the main underlying factors.

Saccharomyces boulardii is a yeast, closely related to baker's yeast. A review of cases published through 2005 identified 92 invasive Saccharomyces infections, of which 72 were found in the blood. Most frequent contributing factors: an intravascular catheter and antibiotic therapy. S. boulardii represented 51.3% of fungemia cases; patients infected with this yeast were more often immunocompetent and had a better prognosis than those infected with other strains. The outcome was favorable in 62% of cases.

This odds ratio of 14 is a retrospective association: it does not measure the risk for a person taking it at home. A case series of four patients published in 2000 sheds light on the mechanism: all patients had a vascular catheter, and opening a sachet contaminated the air, surfaces, and hands. The authors recommend opening sachets and capsules wearing gloves, outside the patient's room.

The 2023 Cochrane review, with 60 trials and 11,156 infants born before 32 weeks or weighing less than 1,500 g, concludes that probiotics could reduce the risk ofnecrotizing enterocolitis, a severe intestinal inflammation, by nearly half (relative risk 0.54, low certainty), and probably reduce mortality somewhat (0.77, moderate certainty). In infants under 1,000 g or extremely premature, no benefit is demonstrated.

Yet the risk exists. In Zurich, three infants under 30 weeks and weighing less than 1,230 g, who received a probiotic containing live Bifidobacterium longum, developed bacteremia from this bacterium; analyses showed an identical profile to the strain in the capsule. In two of them, the bacteremia was transient and did not require antibiotics; the third developed necrotizing enterocolitis despite the probiotic and had to undergo surgery.

A Dutch multicenter trial sought to verify whether a mixture of several probiotic species, administered enterally twice daily for 28 days, would reduce infections during predicted severe acute pancreatitis. The result was opposite to the hypothesis.

These are hospitalized patients in serious condition, receiving a specific mixture enterally within 72 hours of first symptoms: the trial says nothing about a capsule taken by a healthy person. It shows instead that a probiotic is not inert in a very ill patient; the authors conclude that it should not be given in this category of patients.

During antibiotic therapy, their benefit is well established: in children, antibiotic-associated diarrhea affected 8% of participants on probiotics versus 19% of controls, and the effect was more pronounced at 5 billion units per day or more.

A Weizmann Institute study, published in 2018, adds a nuance. In mice and humans, after antibiotic treatment, a multi-strain probiotic delayed and rendered incomplete the reconstitution of the intestine's own microbiota, compared to spontaneous recovery, whereas a transplant of one's own microbiota, called autologous, restored it almost completely in a few days. This specific mixture does not represent all strains.

Direct transfer of a resistance gene from a probiotic strain to a pathogenic bacterium remains primarily theoretical : listed in safety reviews, it was not observed in the study above. What is documented, however, is that a probiotic strain can acquire resistance in a patient, such as the rifampicin resistance mutation found in the Boston study, and that a probiotic can shift the balance of resistance genes already present in the intestine.

Regarding interactions, antibiotics can kill live probiotic bacteria and antifungals can kill a yeast like S. boulardii: a possible loss of efficacy, which no identified study here has measured. In practice, the common habit is to space the probiotic intake a few hours apart from the antibiotic; no identified study here establishes an optimal interval.

Some lactic acid bacteria produceD-lactic acid, a form that the body eliminates slowly. Its accumulation causes acidosis with neurological disorders, known in short bowel syndrome. A case published in 2010 illustrates this: a 5-year-old girl with short bowel syndrome received a probiotic at double dose for diarrhea; two weeks later balance disorders appeared, with a D-lactate level of 5.537 mmol/l. The authors consider the probiotic probably responsible. Conversely, in a boy with the same syndrome, a probiotic mixture eliminated D-lactate-producing lactobacilli within a few weeks and stabilized his condition for more than a year: it all depends on the strains present and those that are introduced.

This study remains debated : small sample size, comparison group of 8 people, lack of medical definition of brain fog, and the authors acknowledge not knowing whether bacterial overgrowth existed before the probiotics. Their conclusion is measured: caution regarding excessive and unclear use, especially in cases of digestive motility disorders or prolonged treatment with antacids or opioids. Our guide on thegut-brain axis addresses these links.

Thehistamine aspect is theoretical. Certain bacteria produce biogenic amines, including histamine, hence strain-by-strain testing in safety evaluations: in one of them, two bifidobacteria strains produced neither histamine, nor tyramine, nor cadaverine. No trial identified via PubMed measured histamine-related symptoms under probiotics in histamine-intolerant individuals. If you have followed histamine intolerance, discuss it with your doctor.

<<<27>>> Bacillus spores spores de Bacillus are dormant and resistant forms of living bacteria, and infections have been described with certain strains. With Bacillus clausii, one case reported prolonged bacteremia of 111 days in an immunocompetent 17-month-old child with no risk factors after brief use; the seven other reported cases of prolonged bacteremia involved patients with other conditions. Another case concerns a non-immunocompromised patient hospitalized for infectious diarrhea and suffering from active ulcers. These are isolated cases, often in fragile situations.

Each strain must be judged on its own data. For Heyndrickxia coagulans MTCC 5856, the LactoSpore strain, published trials are small and conducted by its manufacturer. In 30 healthy adults, of whom 15 received the strain, one capsule per day of 2 billion CFU for 28 days caused no adverse effects, with blood parameters remaining normal. In 36 patients with irritable bowel syndrome with diarrhea, of whom 18 received the strain, 2 billion CFU per day for 90 days, combined with usual treatment, kept biological parameters and vital signs within normal ranges. An analysis of the strain over three years of production found it stable, non-mutagenic, and lacking the enterotoxin genes sought.

In the trial on gas and bloating as well as in the one on irritable bowel syndrome, adults took 2 billion spores of B. coagulans MTCC 5856 per day; our Probiomix provides the same dose, 2 billion LactoSpore spores per day, in two capsules, with 600 mg of acacia fiber. These small 4 to 13-week trials do not replace large-scale monitoring. Probiomix is not recommended for children under 6 years old and for pregnant or breastfeeding women, and should only be considered with medical advice for at-risk individuals described in this guide.

<<<38>>> Postbiotics postbiotiques are, according to the consensus of the International Scientific Association for Probiotics and Prebiotics, preparations of inactivated microorganisms, or their components, that provide a health benefit. This definition attributes them an expected better safety profile, as these microorganisms can no longer multiply and therefore cannot cause bacteremia or fungemia. With two caveats: the safety of a postbiotic cannot be inferred from that of the original bacterium, and each postbiotic must undergo its own safety evaluation before use. The Plenibiotic in Probiomix is of this nature: 50 mg of heat-inactivated Lacticaseibacillus paracasei 327, a bacterium that is no longer viable.

A working group from a European scientific society of pediatric gastroenterology reviewed analyses of commercial probiotics: according to them, discrepancies with the label are "surprisingly frequent": poorly identified strains, non-viable bacteria, colony counts that cannot be verified, and sometimes contamination, including by pathogenic microorganisms.

A Slovenian study illustrates these discrepancies on 26 supplements sold in pharmacies: 3 products (12%) contained too few viable bacteria, two advertised strains actually belonged to another species, and 10% of strains were detected only as DNA, without cultivable bacteria.

In Spain, researchers analyzed 11 probiotics: cow's milk proteins were detected in 10 of them, three of which exceeded 2.5 mg/kg (21, 52 and 112 mg/kg), and egg white proteins in 3, while no label mentioned eggs and one claimed to be milk-free. For a person allergic to milk or eggs, the statement "lactose-free" says nothing about milk proteins.

Pregnancy deserves separate mention. A meta-analysis of 11 randomized trials in 1,505 women showed no effect of lactobacilli and bifidobacteria on the cesarean section rate, birth weight, or gestational age, and no malformations were reported in the probiotic groups. No trial addressed S. boulardii during pregnancy. These data apply to specific strains: during pregnancy and breastfeeding, the advice of the midwife or physician remains the rule, and our Probiomix is not recommended for this purpose.

These rules combine study data and practical advice; they are intended for healthy adults.

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