Bacillus clausii

Bacillus clausii: A Comprehensive Reference

1. Identity and Classification

Nomenclature and Taxonomy

Alkalihalobacillus clausii (synonym Bacillus clausii) is a Gram-positive, rod-shaped, motile, and spore-forming bacterium that lives in the soil but is also a natural microbiota of the mammalian gastrointestinal tract. The organism has undergone repeated reclassification over its taxonomic history. First described in 1995 as Bacillus clausii based on phenetic characteristics from soil isolates, it was reclassified into the novel genus Alkalihalobacillus, and was further reclassified to the genus Shouchella in 2021 (validated 2022) based on additional genomic and phylogenetic evidence. It has been reclassified as Shouchella clausii, and before that it was known as Alkalihalobacillus clausii; however, it is still commonly referred to by the older name Bacillus clausii in clinical literature.

It belongs to the genus Bacillus, which is part of the phylum Firmicutes, and is a Gram-positive, rod-shaped, spore-forming bacterium widely recognized for its probiotic properties. B. clausii is distinguished from other Bacillus species by its ability to produce catalase and its resistance to several antibiotics.

Natural Source and Ecological Origin

Bacillus clausii was originally isolated from soil, and has gained significant attention in clinical, pharmaceutical, and industrial fields due to its robustness, resistance to harsh environmental conditions, and beneficial effects on human health. The type strain, DSM 8716 (equivalent to ATCC 700160), was isolated from garden soil in Denmark and serves as the reference for species delineation.

Historically considered to be soil microorganisms, Bacillus spp. bacteria should be reconsidered as gut commensals because their prevalence in animal feces is now recognized to be greater than previously thought. One study demonstrated diverse Bacillus species in the feces of untreated healthy subjects, with B. clausii reported as the most frequently recovered isolate.

Shouchella clausii is notable for its alkalitolerant nature, enabling growth in alkaline environments with pH values up to 10. It exhibits thermotolerance, thriving between 25–45°C, and demonstrates resilience to harsh conditions such as gastric acidity and bile salts, with survival rates exceeding 88% under simulated gastrointestinal stresses.

Commercially Used Strains

The best-known commercial preparation, Enterogermina® (Sanofi), contains spores of four antibiotic-resistant Bacillus clausii strains: O/C (CNCM I-276), N/R (CNCM I-274), SIN (CNCM I-275), and T (CNCM I-273), and is recommended to restore intestinal microbial balance, particularly during antibiotic treatment. The designations of these bacterial strains are derived from their resistance to diverse antibiotics: O/C is resistant to chloramphenicol, SIN to neomycin and streptomycin, N/R to novobiocin and rifampin, and T to tetracycline. Other named strains used in research include UBBC-07, 088AE, ENTPro, AO1125, and OHRC1.

Dosage Forms and Preparations

There are currently two different formulations available: freeze-dried capsules and liquid vials, marketed in 55 countries around the world for the treatment of gut dysbiosis and the prevention of gastrointestinal infectious diseases. The 5 mL single-dose vials of the oral suspension are suitable for adults and children, and are gluten- and lactose-free. Each vial or capsule of the standard Enterogermina preparation contains 2 billion (2 × 10⁹) spores of polyantibiotic-resistant B. clausii. Spores are greatly resistant to harsh food processing treatment (heat and industrial pressure) and can maintain their physiological traits inside the human gut.

A comparative microbiological and molecular characterization of five commercially available probiotic preparations of B. clausii (Tufpro, Ecogro, Enterogermina, Entromax, and Ospor) showed that some comprise mixed bacterial populations; only Enterogermina (O/C, N/R, SIN, and T) was found to consist of a homogeneous B. clausii population.

Regulatory Status

The European Food Safety Authority (EFSA) has granted Qualified Presumption of Safety (QPS) status to several Bacillus strains, including B. clausii and B. subtilis, recognizing their safety and beneficial effects when used as probiotics. Enterogermina® is a probiotic registered as a pharmaceutical preparation since 1958, with OTC status since 1999.

2. Traditional and Historical Use

Bacillus clausii has been studied and utilized primarily in the 20th and 21st centuries, particularly in pharmaceutical microbiology and probiotic research. While it does not appear in traditional herbal or folk medicine, it has a decades-long history in clinical medicine, especially in Italy and other parts of Europe, where preparations like Enterogermina have been used since the 1960s to treat diarrhea and intestinal flora imbalance.

Spore-forming Bacillus spp. have been used for decades in the form of fermentation products or spore-based probiotic supplements; however, only a few Bacillus strains are recognized as safe and are available for commercial use. Probiotic preparations broadly have been used throughout history — in a Persian version of the Old Testament, Abraham's longevity was purported to be the result of drinking sour milk, and in 76 BC the Roman historian Plinius described fermented milk as a remedy for gastroenteritis. However, these general historical references pertain to fermented foods broadly, not specifically to B. clausii, which as a defined pharmaceutical entity is a product of modern microbiology.

Its use is supported by modern clinical studies, and it is often recommended by physicians alongside or after antibiotic treatments to prevent or reduce gastrointestinal side effects and promote microbiome recovery. Clinically, B. clausii is one of the most commonly used microorganisms of the Bacillus spp.

3. Key Constituents and Active Compounds

The Spore and Vegetative Cell Cycle

Alkalihalobacillus clausii exists in two different forms: dormant spores and active vegetative cells. Vegetative cells are sensitive to extreme environments, such as the human gastrointestinal tract. Because of this, only a small amount of vegetative cell probiotics may reach the intestine unless they are administered in capsules or other protective molds.

Its ability to form endospores allows it to survive extreme conditions, including the acidic environment of the stomach, making it an effective and stable probiotic. Once the spores pass through the upper gastrointestinal tract, they undergo a process called germination. This transforms the dormant spore into a metabolically active vegetative cell, which then begins to multiply and exert its beneficial effects in the gut. The annotation of the genome revealed genes linked to gut colonization, immune system modulation, and stress resistance. In a favorable intestinal environment, the spores germinate and will transition into motile vegetative cells, where A. clausii becomes metabolically active.

Antimicrobial Compounds

Alkalihalobacillus clausii has been found to produce antimicrobial substances that are active against Gram-positive bacteria including Staphylococcus aureus, Enterococcus faecium, and Clostridioides difficile. One significant mechanism involves the production of antimicrobial compounds, such as bacteriocins, which directly inhibit the proliferation of harmful bacteria. The specific bacteriocin, known as clausin, is active against various Gram-positive pathogens, including Staphylococcus aureus and Clostridium difficile. Additionally, genes coding for the bacteriocin gallidermin, which prevents biofilm formation in the pathogens Staphylococcus aureus and S. epidermidis, have been identified in B. clausii ENTPro.

Metabolic Products and Vitamins

Unique metabolic pathways of A. clausii give rise to its probiotic capabilities. It is able to synthesize short-chain fatty acids, B-vitamins, and antioxidant enzymes, all of which promote health in the gastrointestinal tract of humans and other mammals. It produces a range of enzymes, including proteases and amylases, contributing to biotechnological processes, while its spore-forming capability ensures stability in probiotic formulations.

Antibiotic Resistance Determinants

The genes conferring resistance to chloramphenicol, streptomycin, rifampicin, and tetracycline in the B. clausii ENTPro strain could be identified at the genomic level. B. clausii UBBC07 analysis revealed that the antibiotic resistance genes are present in chromosomal DNA which is intrinsic and not transferable. Toxin genes were also found to be absent. The ability of the spores to resist multiple classes of antibiotics enhances their value, allowing them to be administered simultaneously with antibiotic therapy without being destroyed.

Genomic Features

The whole genome sequence of B. clausii 088AE generated a single scaffold of 4,598,457 bp with 44.74 mol% G+C, annotated with 4,371 coding genes, 75 tRNAs, and 22 rRNAs. Gene sequences related to safety and genome stability, including antibiotic resistance genes (840), virulence factors (706), biogenic amines (1), enterotoxin (0), emetic toxin (0), lanthipeptides (4), prophage (4), and CRISPR sequences (11), were identified and evaluated for safety. The absence of enterotoxin and emetic toxin genes is considered significant for the safety profile of this strain.

4. Mechanisms of Action

Colonization and Persistence

Persistence within the GI tract of the B. clausii strains O/C, N/R, SIN, and T has been demonstrated in vivo in a murine model, with declining but detectable levels of the strains in feces beyond 10 days. These data are supported by a randomized, open-label, cross-over trial in which healthy volunteers received a single oral dose of B. clausii (O/C, N/R, SIN, and T) as two formulations (vial and capsule). Bacillus clausii was found alive in fecal samples for over 10 days following administration.

Findings from studies show the ability of B. clausii spores to survive, germinate and grow after acid and bile salt challenge and under restricted oxygen levels, with some evidence of variation in responses between the different strains. Although not traditionally considered a natural inhabitant of the human GI tract, evidence indicates that some Bacillus species can colonize the intestinal epithelium, blurring the boundary between gut resident and transient microbiota. Fundamental attributes of the native bacterial microbiota that confer survival are not essential for Bacillus species, which show additional characteristics, such as tolerance of acids and bile salts in the hostile environment of the GI tract, that support their use as probiotics.

Immunomodulatory Activity

The active cells of B. clausii play a direct role in modulating the host's immune response, which is crucial for maintaining intestinal homeostasis. This involves interacting with immune cells to regulate the production of pro- and anti-inflammatory cytokines. Certain strains have been shown to induce pro-inflammatory cytokines like interferon-gamma (IFN-γ) and stimulate the proliferation of CD4+ T cells, supporting the body's defenses against infection.

In children with allergic rhinitis, administration of B. clausii (O/C, SIN, N/R, T) results in a significant decrease in IL-4 levels and a significant increase in IFN-γ, IL-12, TGF-β, and IL-10 levels. In adults with allergic rhinitis, B. clausii (O/C, SIN, N/R, T) administration leads to an increase in the levels of IFN-γ, TGF-β, and IL-10, and a decrease in the levels of IL-4. High levels of IL-4, IL-5, and IL-13 are indicative of Th2 polarization, while high levels of IL-10 and TGF-β are characteristic of Th1 and Treg polarization.

A study by Di Caro and colleagues showed that S. clausii was able to modulate the expression of genes involved in immune response, inflammation, cell growth, apoptosis, cell differentiation, cell adhesion, and cell-to-cell signalling in duodenal mucosal cells isolated from patients with mild oesophagitis.

Anti-Rotavirus Mechanisms

B. clausii inhibited reactive oxygen species production and release of pro-inflammatory cytokines (interleukin-8 and interferon-β) in Rotavirus-infected cells, and down-regulated pro-inflammatory Toll-like receptor 3 pathway gene expression. Such mechanisms likely contributed to the observed protective effects of B. clausii against reduced cell proliferation and increased apoptosis in Rotavirus-infected enterocytes.

5. Scientific Evidence by Area of Use

5.1 Acute Diarrhea in Children

This is the area with the strongest and most replicated clinical evidence for B. clausii.

A 2018 systematic review and meta-analysis (six randomized controlled trials, 1,298 patients) found that Bacillus clausii significantly reduced the duration of diarrhea (mean difference = −9.12 h; 95% CI: −16.49 to −1.75, p = 0.015) and the duration of hospitalization (mean difference = −0.85 days; 95% CI: −1.56 to −0.15, p = 0.017) compared with control. There was also a trend of decreasing stool frequency after Bacillus clausii administration.

A more recent systematic review and meta-analysis focused specifically on the Enterogermina® preparation (O/C, SIN, N/R, and T strains), identifying 11 randomized and three non-randomized controlled trials. The duration of diarrhea was reduced by 0.6 Hedge's g, the number of stools by 0.34 Hedge's g, and the duration of hospital stay by 0.27 Hedge's g (p < 0.05 for all three parameters). Several other parameters also appeared improved. Adverse events were absent or similarly present in the B. clausii and control groups. The authors concluded that the B. clausii preparation is an effective and well-tolerated treatment of acute gastroenteritis in children; however, more high-quality randomized controlled trials are needed, particularly in comparison to other probiotics.

A large-scale, open-label study (CODDLE) in Filipino children confirmed clinical utility. In more than half of the per-protocol population (1,535/2,916; 52.6%), diarrhea was resolved within the first 3 days of treatment with Bacillus clausii. There was no significant difference in mean diarrhea duration between patients with antibiotic-associated (3.3 ± 1.3 days) or viral diarrhea (3.4 ± 1.3 days). Bacillus clausii significantly reduced the mean number of stools per day, from 5.2 ± 2.0 stools at baseline to 1.2 ± 0.6 stools at study end (p < 0.001). The proportion of patients with loose stools decreased from 81.6% at baseline to 9.2% at end of treatment.

Limitation: Several probiotics have become guideline-recommended treatments for acute gastroenteritis in children, but no recommendation was made for Bacillus clausii preparations on the basis of too limited data at the time of those guidelines.

5.2 Acute Diarrhea in Adults

In a prospective Phase II clinical trial of Bacillus clausii in 27 adult patients with acute diarrhea, the mean duration of diarrhea decreased from 34.81 ± 4.69 minutes at baseline to 9.26 ± 3.05 minutes per day after 10 days of Bacillus clausii therapy (p < 0.0001). The mean frequency of defecation decreased from 6.96 ± 1.05 to 1.78 ± 0.50 times per day (p < 0.0001), abdominal pain decreased significantly, and stool consistency improved from watery to soft. No significant change in safety parameters was observed.

Limitation: This adult trial was small (n = 27) and uncontrolled. Larger, placebo-controlled adult trials are lacking.

5.3 Antibiotic-Associated Diarrhea (AAD)

Dysbiosis and antibiotic-associated diarrhea (AAD) are significant concerns in clinical settings. Probiotics such as Bacillus clausii (O/C, N/R, SIN, T), a spore-forming bacterium resistant to gastrointestinal conditions and most commonly used antibiotics, emerge as a promising approach for preventing AAD in children and adults during antibiotic therapy.

A 2025 systematic review included a total of four studies (two randomized controlled trials, one meta-analysis of RCTs, and one expert consensus). Several authors of that review declared conflicts of interest, including honoraria from Sanofi (manufacturer of Enterogermina®), and one author was a Sanofi employee, while funding for the medical writing was provided by Opella, a Sanofi company — a limitation that should be considered when weighing this review's conclusions.

In an early pediatric study, in 35 children (aged 3–24 months) with extraintestinal disease, treatment with antibiotics for respiratory or urinary infections was stopped because of diarrhea in 2/8 subjects receiving only antibiotics, and the number of stools per day increased in most of these subjects; in contrast, the daily number of stools, and their appearance, was normal in children (n = 11) who also received B. clausii (O/C, N/R, SIN and T; 4 × 10⁹ CFU/day for 5 days).

Limitation: The body of evidence for AAD specifically remains small. A systematic review of published trials evaluating probiotic use for the prevention or treatment of various diseases concluded that the degree of dysbiosis improvement is dependent on the enrolled population and timing of microbiological assays, and that the claim for correcting dysbiosis is poorly supported for most probiotic strains and requires further research.

5.4 Helicobacter pylori Eradication Therapy

Antibiotic treatment can alter the gut microbiome and cause short-term gastrointestinal adverse effects. A randomized, double-blind, single-center, Phase IIIB study assessed the efficacy of lyophilized capsules containing 2 × 10⁹ spores of Bacillus clausii (Enterogermina®; Sanofi Synthelabo) in reducing adverse effects associated with Helicobacter pylori eradication therapy in Italy, enrolling 130 adult outpatients with H. pylori infection assigned to receive one Enterogermina® capsule or placebo three times daily for 2 weeks. The incidence of diarrhea in week 1 was 29% in the B. clausii group and 48% in the placebo group [relative risk (RR) 0.61; 95% CI 0.39–0.97; p = 0.03]. No differences were noted in other GI symptoms during the first 7 days; however, epigastric pain was significantly lower at week 2 with the probiotic compared with placebo (p = 0.037). B. clausii was well tolerated, with only patient-reported skin rash intensity being greater at week 2 than with placebo (p = 0.008).

According to World Gastroenterology Organization guidelines, data suggest that probiotics as adjuvant therapy may be helpful in H. pylori eradication (level 1b evidence), but data are insufficient to support probiotic monotherapy as an effective eradication strategy.

5.5 Small Intestinal Bacterial Overgrowth (SIBO)

The use of B. clausii for SIBO decontamination was assessed in 40 adults with chronic bloating, flatulence, abdominal discomfort or pain, and diarrhea plus an abnormal hydrogen glucose breath test, which is indicative of the presence of SIBO. Participants received Bacillus clausii therapy three times daily for a month. There was 47% decontamination with the probiotic use. One patient reported constipation as an adverse effect.

Limitation: This was a single small trial (n = 40) without a placebo group; the evidence for SIBO is preliminary and insufficient to draw definitive conclusions.

5.6 Recurrent Respiratory Infections in Children

A pilot study assessed the efficacy and safety of 3-month treatment with Bacillus clausii in the prevention of recurrent respiratory infections (RRI) in children. Eighty children with RRI were studied: 40 were randomly treated with B. clausii for 3 months and followed up for a further 3 months; 40 were included in the control group. Children treated with B. clausii had shorter duration of respiratory infection in comparison with the control group both during the treatment phase (mean 11.7 days vs. 14.37; p = 0.037) and the follow-up period (mean 6.6 days vs. 10.92; p = 0.049). This effect was evident also in allergic children during the follow-up.

In a pilot study of children aged three to six years, the administration of B. clausii (O/C, SIN, N/R, T) over a three-month period has been shown to significantly reduce the number and duration of respiratory infections in comparison to the control group, over the study and follow-up periods.

Limitation: Very few studies have investigated the effect of A. clausii on respiratory infections or established the therapeutic efficacy against ailments related to allergic rhinitis. The available studies are small pilot trials and should be considered preliminary.

5.7 Allergic Rhinitis

B. clausii was found safe and effective at a dose of 6 billion CFU/day for 3 weeks in children with allergic rhinitis. In children with allergic rhinitis, administration of B. clausii (O/C, SIN, N/R, T) results in a significant decrease in IL-4 levels and a significant increase in IFN-γ, IL-12, TGF-β, and IL-10 levels. Probiotics have been shown to have clinical management potential in allergic rhinitis through immunomodulation.

Limitation: Evidence in this area is limited to pilot studies with small sample sizes. No large-scale, multi-center RCTs have been published specifically for this indication.

5.8 Prevention of Late-Onset Sepsis in Preterm Neonates

Prophylactic administration of B. clausii to reduce the risk of late-onset sepsis in preterm infants was assessed in a double-blind, randomized, placebo-controlled trial in 244 preterm neonates. B. clausii has been used safely for up to 6 weeks in preterm infants (less than 34 weeks' gestational age) in this clinical study.

B. clausii probiotics have been used safely for several decades and have been shown to improve outcomes in acute pediatric diarrhea, rotavirus infections, necrotizing enterocolitis and late-onset sepsis, H. pylori treatment, and respiratory tract infections and allergic rhinitis.

5.9 Protein Absorption and Amino Acids

The effect of the UBBC-07 strain on protein absorption had not previously been investigated; researchers hypothesized that Bacillus clausii supplementation may enhance protein absorption by promoting gut health, increasing digestive enzyme activity, and modulating gut microbiota, thereby leading to increased bioavailability of essential amino acids (EAAs) and their utilization. A double-blind, randomized, controlled trial assessed the impact of Bacillus clausii UBBC-07 consumed in combination with whey protein on circulating EAAs and muscle strength in those involved in sports. Seventy healthy subjects between 18 and 28 years of age who were involved in regular exercise were included in the study. This area of investigation is very early-stage, and no firm conclusions can be drawn from a single trial.

6. Body Systems Associated

• Gastrointestinal system: The primary and most extensively studied area. Includes acute and antibiotic-associated diarrhea, SIBO, gut microbiome restoration, and reduction of H. pylori therapy-associated GI adverse effects.
• Immune system: It is classified as a probiotic microorganism that maintains a symbiotic relationship with the host organism. Immunomodulatory activity through cytokine regulation (IFN-γ, IL-4, IL-10, IL-12, TGF-β) has been demonstrated in both in vitro and clinical settings.
• Respiratory system: It is currently being studied in relation to respiratory infections and some gastrointestinal disorders.
• Musculoskeletal/Nutritional: Early clinical evidence suggests a possible role in enhancing amino acid bioavailability in athletes when combined with whey protein supplementation.

7. Dosages Reported in Studies

The following dosages are drawn directly from clinical studies and product information; they are not recommendations.

• In the Helicobacter pylori RCT, patients received one Enterogermina® capsule (containing 2 × 10⁹ spores of polyantibiotic-resistant B. clausii) three times daily (for a total of 6 × 10⁹ CFU per day) for 2 weeks.
• In a preterm neonates study, B. clausii (Enterogermina 2 × 10⁹ spores per 5 mL oral suspension) was administered at 2 mL every 8 hours mixed with enteral feeds (delivering 2.4 × 10⁹ spores per day) until postnatal age of 6 weeks, discharge, death, or occurrence of late-onset sepsis, whichever occurred first.
• In a SIBO decontamination study, B. clausii (Enterogermina) 1 vial (2 × 10⁹ spores) was given orally 3 times daily for 1 month.
• In a respiratory infections study in children aged 3 to 6 years, B. clausii (Enterogermina) 1 vial (2 × 10⁹ spores per 5 mL oral suspension) was given orally twice daily for 90 days.
• In the CODDLE large-scale open-label study, eligible subjects were treated with one to two vials of Bacillus clausii (Erceflora®) per day for 5 to 7 days depending on the age of the child and severity of diarrhea, with each 5 mL vial containing 2 billion spores.
• In a persistent diarrhea study in young children, a high dosage of approximately 10 billion CFU daily as recommended by the World Gastroenterology Organization for supportive treatment was selected.
• In a pediatric antibiotic-associated diarrhea study, children received B. clausii (O/C, N/R, SIN and T) at 4 × 10⁹ CFU/day for 5 days.
• The Enterogermina® product information lists dosages of: adults — 2–3 vials per day or 2–3 capsules per day; children — 1–2 vials per day or 1–2 capsules per day; infants — 1–2 vials per day.

8. Safety Considerations and Interactions

General Tolerability

Systematic review findings suggest that treatment with Bacillus clausii is well tolerated, without causing serious adverse events in the general population studied in clinical trials. A. clausii AO1125 showed no pathogenicity, cytotoxicity, or hemolytic activity and was well-tolerated in clinical settings, with mild, transient abdominal gas; the absence of important adverse effects and clinical parameters in the normal range of all patients indicate that this probiotic strain could be used in dietary supplements.

Bacteremia and Sepsis (Serious Adverse Events)

Several cases of B. clausii bacteremia, at least one of which was fatal, have been reported in infants and adults subsequent to B. clausii probiotic use. Cases of bacteremia, septicemia, and sepsis have been reported in immunocompromised or critically ill patients and in preterm neonates since the introduction of Enterogermina into the market. In some critically ill patients, the outcome was fatal. Enterogermina should be avoided in these groups of patients.

In most cases, related adverse events are few and not life-threatening. However, cases of bacteremia associated with the use of these substances have been described, mainly in the pediatric population in which their prescription is more common. Cases of bacteremia and sepsis have also been documented in immunocompetent and immunocompromised adult patients following the use of probiotics. In reported cases, patients who received probiotics with Bacillus clausii spores during their stay in the intensive care unit subsequently developed sepsis and blood-culture-documented bacteremia.

The use of probiotics as concomitant treatment in patients with some degree of immunosuppression should be administered with caution, considering the presence of risk criteria for complications such as malnutrition or intestinal epithelial damage due to severe diarrhea, since they predispose to the development of bacteremia and/or sepsis.

Antibiotic Resistance Gene Transfer

B. clausii has intrinsic resistance genes to different classes of antibiotics, such as cephalosporins, macrolides, and aminoglycosides, which could pose a problem in the future since bacteria can share resistance genes. Widespread use of probiotic bacteria in conjunction with antibiotic use can over time establish a reservoir of antibiotic resistant genes in probiotic bacteria. While intrinsic antibiotic resistance can be a desirable trait as probiotics help restore host gut microflora during a course of antibiotics, the transfer of resistant genes to humans offers serious clinical threats. However, analysis of B. clausii UBBC07 revealed that the antibiotic resistance genes are present in chromosomal DNA which is intrinsic and not transferable, at least for that particular strain — though strain-to-strain variation in resistance gene location has been documented across commercial preparations.

Anaphylaxis with Incorrect Administration Route

Incorrect use of the medicinal product has caused serious anaphylactic reactions such as anaphylactic shock. This medicine is for oral use only. Do not inject or administer by other routes; incorrect use of the medicinal product has resulted in severe anaphylactic reactions such as anaphylactic shock.

Drug Interactions

Antibiotics may diminish the therapeutic effect of B. clausii. Consider therapy modification. To mitigate this interaction, during antibiotic therapy, it is advisable to administer the preparation in the interval between one antibiotic administration and the other. No formal interaction studies have been performed.

Pregnancy and Special Populations

B. clausii can be used during pregnancy and lactation, and in breastfeeding infants according to available product information, though Enterogermina® should be used during pregnancy and breastfeeding only if the potential benefits outweigh the potential risks. In 2014, the Food and Drug Administration issued a warning that advises practitioners of the potential risks of using dietary supplements containing live bacteria or yeast in immunocompromised patients (e.g., premature infants).

Regulatory Safety Acknowledgements

Probiotics must meet certain characteristics, such as absence or very low virulence, and be classified as "generally safe" by the FDA and as "qualified presumption of safety" by EFSA. The EFSA presumes that Bacillus clausii (O/C, N/R, SIN, and T) contained in Enterogermina® is safe and has been added to the Qualified Presumption of Safety (QPS) list.

References

• Genetic and phenotypic assessments for the safety of probiotic Bacillus clausii 088AE — PMC/NCBI
• Alkalihalobacillus clausii — Wikipedia
• Robust and safe: Unveiling Bacillus clausii OHRC1's potential as a versatile probiotic — ScienceDirect
• Alkalihalobacillus clausii spores lessen antibiotic-induced intestinal injury — ScienceDirect
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• Supplementation With Bacillus clausii UBBC-07 Enhances Circulating Essential Amino Acids in Young Adults: A Double-Blind, Randomized, Controlled Trial — PMC/NCBI
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