Pediococcus acidilactici

Pediococcus acidilactici: A Comprehensive Reference

1. Identity and Classification

Taxonomic Identity

Pediococcus acidilactici belongs to the domain Bacteria, phylum Firmicutes (also referred to as Bacillota under recent nomenclature), class Bacilli, order Lactobacillales, and family Lactobacillaceae (historically placed in Pediococcaceae in older literature). It is classified among the homofermentative lactic acid cocci. Pediococcus acidilactici is a species of Gram-positive cocci that is often found in pairs or tetrads. The genus Pediococcus is distinguished by cells that divide in two planes, forming tetrads, unlike the rod-shaped morphology of Lactobacillus.

The scientific classification is: Domain: Bacteria; Phylum: Firmicutes; Class: Bacilli; Order: Lactobacillales; Family: Lactobacillaceae; Genus: Pediococcus; Species: acidilactici. As a living microorganism, no single chemical formula applies; its genomic size is commonly approximately 2.0–2.5 Mbp with a GC content of approximately 40–45%.

Within the genus Pediococcus, P. acidilactici and P. pentosaceus are the two species most relevant to human health and most extensively studied as probiotics. The two species share considerable genetic and phenotypic overlap, but can be reliably distinguished by pheS gene sequencing—a molecular tool used in taxonomic identification studies.

Strain Designations and Common Names

P. acidilactici has strain-specific designations, with catalog numbers varying by strain (e.g., ATCC, DSM, CECT, NCIMB, MTCC). Common probiotic trade names include formulation-specific brand names that contain P. acidilactici. Notable strain names and trade designations include: scientific name Pediococcus acidilactici; common trade names Bactocell, pA1c, and Pediocin producer; feed additive designations CNCM I-4622 and DSM 33758; and strain-specific names P10, SY21, SY22, and PA 1.

Natural Sources

P. acidilactici is naturally found in spontaneously fermented vegetables, meat and dairy fermentations, sourdough, plant surfaces, and animal gastrointestinal tracts. Pediococci are often found in foods from plant fermentation processes such as beer, cider, silage, sauerkraut, and other fermented vegetables. They are also found in other fermented foods such as cheese, as well as in cured meats, raw sausages, and fresh and marinated fish.

Strains of P. acidilactici have been isolated from traditional foods such as Nhang, a traditional Thai-style fermented beef. The bacterium has also been recovered from Bhaati jaanr, an ethnic fermented rice beverage popularly consumed in sub-Himalayan regions, where a strain was isolated based on high butyrate production. MALDI-TOF MS and 16S rRNA gene sequencing confirmed its identity as Pediococcus acidilactici. P. acidilactici is a potential probiotic bacterium isolated from diverse sources; however, strains isolated from milk, especially from raw milk of healthy cows, have not been as thoroughly studied.

Physiological Characteristics

P. acidilactici is a homofermentative bacterium that can grow in a wide range of pH, temperature, and osmotic pressure, therefore being able to colonize the digestive tract. Pediococcus acidilactici grows well on de Man, Rogosa, Sharpe agar at an optimum pH of 6.2, with an overnight incubation at 37 and 45°C. It is also viable at higher temperatures up to 65°C. This species is also acidophilic, and viable at very low pH.

Strains of P. acidilactici are able to metabolize a variety of carbohydrates, including glucose, ribose, xylose, fructose, and galactose to DL-lactate, accompanied by pH reduction as low as 3.6. These organisms are characterized by their ability to ferment carbohydrates primarily into lactic acid, are catalase negative, and are generally recognized as safe.

Common Forms and Preparations

Industrial production uses controlled fermentation, concentration, protective excipients and drying (lyophilization or spray-drying) with GMP seed banks and viability testing. Formulation of P. acidilactici for use as a feed additive employs viable cells as a dry powder or coated granules. For human use, the organism is marketed in capsule, powder, and fermented food forms. While it is possible to administer Pediococcus acidilactici alone, the bacterium is typically administered as part of a product, in particular as a component of a food product, a dietary supplement, or a pharmaceutical formulation.

2. Traditional and Historical Use

Pediococci are lactic acid bacteria that have been used for centuries in the production of traditional fermented foods, and their fermentative abilities were explored by the modern food processing industry in the use of pediococci as starter cultures.

Traditional use was not as isolated pure cultures but as part of mixed fermentation microbiota. Pediococcus-like organisms have been present in traditional fermented foods for centuries (vegetable ferments, sourdough, some meat and dairy fermentations). Their presence contributed to acidification, flavor development, and food preservation.

By the modern era of food science, P. acidilactici had been intentionally deployed as a starter culture in semihard cheese production, sauerkraut fermentation, dry-cured sausages, and even agricultural silage. The Bulletin of the International Dairy Federation (Bourdichon et al., 2018) describes the application of Pediococcus spp. as starter cultures in fermented food products as follows: P. acidilactici in dairy and meat, P. pentosaceus in meat, fish, dairy, beer, wine, fruit, vegetable, and beverages.

A bacteriocin produced by Pediococcus acidilactici has been characterized from Alheira, a fermented sausage traditionally produced in Portugal. Certain species of Pediococcus such as P. acidilactici are used as starter cultures in salami as they ferment glucose, mannose, and fructose into acid (mainly lactic acid) without producing gas.

In recent years, traditional manufactured fermented foods such as cured sausages, cheeses, nham, and sucuk from all over the world have been examined for bacteriocin-producing LABs with bioprotective application in food.

3. Key Constituents and Active Compounds

Pediocins (Bacteriocins)

Bacteriocins of Pediococcus species are designated as pediocins and produced by three species that play an important role in food biopreservation, including P. acidilactici, P. cerevisiae, and P. pentosaceus. They generally belong to the Class IIa bacteriocin family with a small molecular weight (less than 5 kDa); the identified N-terminal region of all pediocins includes a pattern known as the "pediocin box." They show a wide range of antimicrobial activity against other bacteria related to food spoilage and health hazards of food source.

Pediocin, a cationic peptide, is a strong antimicrobial peptide produced in Pediococcus species. It is strongly active against Listeria monocytogenes and induces cell autolysis by forming a protein complex on cytoplasmic membranes. Pediocin PA-1 is a bacteriocin produced by Pediococcus acidilactici PAC1.0. It kills sensitive pediococcal cells and acts on the cytoplasmic membrane. Pediocin and pediocin-like bacteriocins exert a broad spectrum of antimicrobial activity against Gram-positive bacteria, especially against pathogenic bacteria such as Listeria monocytogenes, through formation of pores in the cytoplasmic membrane and cell membrane dysfunction.

Pediocin PA-1 is a potent inhibitor of Listeria monocytogenes (MIC = 6.8 nM), similar in potency to the bacteriocin produced naturally by Pediococcus acidilactici. When subjected to electrospray LC-MS analysis, the protein was found to be highly pure, with a molecular weight of 4,618 Da. High concentrations of the bacteriocin (greater than 50 units/mL) showed good resistance to extremes of pH (1–12) and temperature (up to 121°C).

Lactic Acid and Other Metabolites

P. acidilactici emerged in comparative genomic analysis as the most versatile species in its genus, harboring genes for adhesion, acid-bile tolerance, oxidative stress defense, vitamin biosynthesis, and γ-aminobutyric acid (GABA) metabolism.

Mechanistically, P. acidilactici has been shown to enhance intestinal barrier integrity by upregulating the expression of tight junction proteins, thereby preventing the systemic translocation of endotoxins such as lipopolysaccharides. Furthermore, it actively alters the intestinal metabolome by producing short-chain fatty acids (SCFAs) and metabolizing tryptophan into neuroactive compounds like indole-3-lactic acid (ILA).

CRISPR-Cas Systems and Genomic Features

A genomic study of P. acidilactici HN9 identified a 2,034,522 bp circular chromosome and two circular plasmids. Two CRISPR regions were identified, including a type II-A CRISPR/CRISPR-associated (Cas) system. Modern genomic research has validated its resilience under gastrointestinal conditions and identified unique features such as a functional CRISPR-Cas system in certain strains.

4. Mechanisms of Action

Antimicrobial and Pathogen Exclusion

Pediocin and pediocin-like bacteriocins exert broad-spectrum antimicrobial activity against Gram-positive bacteria through formation of pores in the cytoplasmic membrane and resulting cell membrane dysfunction. The bacteriocin from P. acidilactici inhibited a large number of bacteria, including Staphylococcus aureus, Listeria monocytogenes, Clostridium perfringens, and Bacillus coagulans.

P. acidilactici CCFM18 had sufficiently strong antimicrobial activity to effectively inhibit the growth of indicator bacteria and enhance their intracellular reactive oxygen species (ROS) level. MALDI-TOF imaging mass spectrometry indicated that this strain increased the production of pediocin PA-1 and the penocin A profile during its interaction with indicator bacteria.

Data suggest that pediocin PA-1 functions in a voltage-independent manner but requires a specific protein in the target membrane.

Gut Barrier Enhancement

P. acidilactici has been shown to enhance intestinal barrier integrity by upregulating the expression of tight junction proteins, thereby preventing the systemic translocation of endotoxins such as lipopolysaccharides.

Metabolic and Signaling Pathways

Gene expression analyses demonstrated that the probiotic metabolic syndrome-alleviating activities of P. acidilactici CECT9879 (pA1c) were mediated by modulation of the insulin/IGF-1 signaling pathway (IIS) through the reversion of the glucose-nuclear-localization of daf-16 and the overexpression of ins-6 and daf-16 mediators, increased expression of fatty acid peroxisomal β-oxidation genes, and downregulation of fatty acid biosynthesis key genes.

P. acidilactici FZU106 significantly regulated the mRNA levels of liver genes (including CD36, CYP7A1, SREBP-1c, BSEP, LDLr, and HMGCR) involved in lipid metabolism and bile acid homeostasis.

Functional analysis of gut microbiota following CCFM6432 supplementation indicated reduced activity in the NOD-like receptor signaling pathway, suggesting anti-inflammatory effects induced by the probiotic. Metabolomic profiling identified elevated levels of fecal lactic acid, which correlated with lower Hospital Anxiety and Depression Scale (HADS) scores, thereby linking probiotic metabolism to mood enhancement.

Microbiota Modulation

Intestinal microbiota profiling by high-throughput sequencing demonstrated that P. acidilactici FZU106 intervention increased the proportion of Butyricicoccus, Pediococcus, Rothia, Globicatella, and [Eubacterium]_coprostanoligenes group, and decreased the proportion of potentially undesirable genera including Corynebacterium_1, Psychrobacter, Oscillospira, and others in high-fat diet-fed rats.

5. Scientific Evidence by Area of Use

5.1 Gastrointestinal Survival and Colonization

A study aimed to investigate the probiotic nature of P. acidilactici MTCC5101 by an in vitro assay of bacterial adhesion to intestinal epithelial cells of the human GI tract using Caco-2 cell line. To assess in vivo survival, oral feeding was carried out with 10 healthy volunteers. The effect on wellness was assessed by studying blood biochemical parameters. Survival was assessed using PCR-based detection in fecal samples. The probiotic nature of the strain was strengthened by its adherence to the intestinal epithelial Caco-2 cell line. The oral feeding study showed the strain to be established in the GI tract, surviving for about 2 weeks after feeding.

The in vivo study enrolled 10 healthy volunteers after informed consent. It was a controlled study consisting of parallel 6-week trials, with 4 weeks of intervention and 2 weeks of washout period. Cells at a concentration of 10⁸–10¹⁰ cells/mL were added to fresh buttermilk for oral feeding, administered once a day for 4 weeks continuously.

Evidence strength: This represents a small-scale (n=10), non-placebo-controlled pilot study. Results demonstrate proof of gastrointestinal survivability and colonization potential, but are insufficient to establish clinical efficacy on their own.

5.2 Irritable Bowel Syndrome

A 2024 human clinical trial in patients with diarrhea-predominant or mixed irritable bowel syndrome (IBS) reported that a probiotic formulation including P. acidilactici CECT 7483 reduced IBS severity scores by a mean of 146.6 points (P < 0.0001), with 62.9% of participants achieving ≥50% symptom improvement, alongside enhanced quality of life.

Evidence strength: This was a multi-strain formulation, so the contribution of P. acidilactici CECT 7483 specifically cannot be isolated from the overall formulation effect. Further strain-specific trials are needed.

5.3 Gut Health and Microbiota Composition in Older Adults

A study aimed to evaluate whether supplementation with P. acidilactici PA53, through modulation of the gut microbiota, could improve emotional well-being in healthy older adults. In an 8-week randomized, double-blind, placebo-controlled trial, 75 older adults (aged 55–70) received either a placebo (maltodextrin) or PA53 (maltodextrin plus 30 billion CFU/day). Fecal microbiota (16S rRNA sequencing) and serum biomarkers (ELISA) were assessed at baseline and week 8. Data were analyzed using t-tests or non-parametric tests and PERMANOVA, with p < 0.05 considered statistically significant.

P. acidilactici PA53 emerged as a safe and effective intervention for enhancing digestive function and modulating inflammatory pathways in older adults. Its ability to enrich beneficial microbiota while suppressing pro-inflammatory taxa aligns with mechanistic insights from animal studies. Comparing to Lactobacillus or Bifidobacterium, the unique advantages of Pediococcus (acid resistance and colonization ability) make it more promising in the elderly group. However, previous research focused on animal studies, and research on its probiotic potential in elderly humans was scarce prior to this trial.

Evidence strength: A well-designed RCT with 75 participants and use of validated biomarker and microbiota methods. Limitations include a single trial and a relatively short duration of 8 weeks.

5.4 Mental Health and the Gut-Brain Axis

Accumulating evidence highlights the crucial role of the "gut-brain axis" in brain health. A study assessed the effects of P. acidilactici CCFM6432 on mood, sleep, and gastrointestinal function in patients with depressive disorder. This clinical trial was a randomized, placebo-controlled study (Registration: ChiCTR2300071025). It enrolled 39 adult patients diagnosed with depressive disorder, randomly assigned to either the placebo control group (n=19) or the CCFM6432 intervention group (n=20). The intervention period spanned four weeks.

In comparison to the placebo, treatment with CCFM6432 significantly decreased depression and anxiety scores and ameliorated gastrointestinal symptoms. Microbiota analysis revealed an increase in species richness without notable changes in overall diversity, yet Pediococcus species was found to be more abundant post-treatment. Functional analysis indicated reduced activity in the NOD-like receptor signaling pathway, suggesting anti-inflammatory effects induced by the probiotic. Metabolomic profiling identified elevated levels of fecal lactic acid, which correlated with lower HADS scores. These findings imply that CCFM6432 may improve brain function by modulating gut microbiota and their mediated immune homeostasis, underscoring its potential as an adjunctive treatment for mental disorders.

Building on prior randomized evidence of clinical benefit with CCFM6432, an extended trial investigated peripheral immune and central reward correlates of treatment response. The aim was to evaluate whether add-on CCFM6432 alleviates anhedonia through immune-inflammatory modulation. Adults with major depressive disorder and anhedonia received standard antidepressant therapy plus CCFM6432 or plus placebo for 30 days. The findings provided preliminary clinical support that immune-inflammatory modulation may contribute to the anhedonia-relieving effects of CCFM6432, particularly in reward anticipation. Larger multicenter studies with multimodal endpoints were warranted to confirm these results and elucidate mechanistic pathways.

Evidence strength: Small sample sizes (n=19–20 per group), short intervention periods (4 weeks), and limited to single-center studies. Results are preliminary and promising; larger, longer confirmatory trials are needed.

5.5 Metabolic Syndrome, Obesity, and Lipid Metabolism

A study investigated the ameliorative effects of P. acidilactici FZU106, isolated from the traditional brewing of Hongqu rice wine, on lipid metabolism and intestinal microbiota in high-fat diet (HFD)-induced hyperlipidemic rats. Results showed that FZU106 intervention inhibited the abnormal increase of body weight, ameliorated serum and liver biochemical parameters related to lipid metabolism and oxidative stress. Histopathological evaluation showed that P. acidilactici FZU106 could significantly reduce excessive lipid accumulation in the liver caused by HFD feeding. Furthermore, FZU106 intervention significantly increased short-chain fatty acid (SCFA) levels in HFD-fed rats, which was closely related to changes in intestinal microbial composition and metabolism.

In a model using Caenorhabditis elegans under high-glucose conditions, supplementation with P. acidilactici CECT9879 (pA1c) reduced fat accumulation in nematode growth medium and in high-glucose medium. Moreover, treatment with pA1c counteracted the effect of high glucose by reducing reactive oxygen species by 20%, retarding the aging process, and extending nematode median survival by more than 2 days in comparison with untreated control worms.

Evidence strength: These findings are restricted to animal and invertebrate models. Human RCT evidence on metabolic parameters remains limited for this species.

5.6 Type 2 Diabetes — Preclinical Evidence and Metformin Synergy

A preclinical study aimed to assess the antidiabetic properties of P. acidilactici pA1c in a murine model of high-fat diet-induced type 2 diabetes. C57BL/6 mice were given HFD enriched with either probiotic (1 × 10¹⁰ CFU/day) or placebo for 12 weeks. Measurements included body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile.

These findings indicated that pA1c improved HFD-induced T2D-derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, the study proposed that pA1c may be a promising new dietary management strategy to improve metabolic disorders in prediabetes and T2D. The authors acknowledged that this was a preliminary, proof-of-concept investigation, and the application of pA1c in a future clinical trial would help elucidate whether the benefits observed in this animal model are transferable to pre-diabetic and diabetic patients.

Pediococcus acidilactici pA1c® has been shown in preclinical research to potentiate metformin efficacy.

Evidence strength: Evidence is currently limited to animal (rodent) and invertebrate models. No human RCTs specifically examining glycemic outcomes with P. acidilactici as monotherapy have been published as of this writing.

5.7 Heavy Metal Detoxification

A 2022 randomized, double-blind trial in 152 workers exposed to occupational heavy metals found that 12 weeks of yogurt containing P. acidilactici GR-1 reduced blood copper levels by 34.45% (from 1246 to 817 μg/L, P < 0.0001) and nickel by 38.34% (from 4.855 to 2.994 μg/L, P < 0.0001), primarily through increased fecal excretion and elevated SCFA levels.

Evidence strength: A moderately sized RCT (n=152) with objective biomarker outcomes. The probiotic was delivered within yogurt rather than as an isolated supplement, and the strain GR-1 is not interchangeable with other P. acidilactici strains. Replication is needed.

5.8 Vaginal Health

In one clinical trial, 95 women (39 with bacterial vaginosis, 45 with vulvovaginal candidiasis, and 11 with both infections) were randomized to receive a vaginal capsule containing L. gasseri LN40, L. fermentum LN99, L. casei rhamnosus LN113, and P. acidilactici LN23 (10⁸–10¹⁰ CFU), or placebo for 5 days after conventional treatment. Probiotic strains were present in vaginal cultures 2 to 3 days after administration (53% colonized after one menstruation). Ninety-three percent of women in the probiotic group were cured after 2 to 3 days compared with 83% in the placebo group (78% vs. 71% after first menstruation). The probiotic group also had significantly less malodorous discharge.

Evidence strength: This was a multi-strain preparation administered vaginally; the contribution of P. acidilactici LN23 specifically cannot be separated from the other strains. Results are preliminary.

5.9 Inflammatory Bowel Disease (Preclinical)

Researchers investigated the anti-inflammatory effect of P. acidilactici SK2, a novel wild-type potential probiotic strain isolated from the human gastrointestinal tract, in the dextran sodium sulfate (DSS)-induced murine model of ulcerative colitis. Mice received dietary supplementation containing P. acidilactici SK2 cells at a daily dose of 10⁹ CFU and were subjected to DSS administration.

Evidence strength: Animal model only; no human clinical evidence for IBD is currently available.

5.10 Food Safety and Biopreservation

Pediocin may be effective in controlling Listeria in milk and during fermentation of turkey summer sausage. Both P. acidilactici and P. pentosaceus may control the growth of Yersinia enterocolitica serotype O:3 and O:8 in fermenting meat. Due to the sensitivity of these compounds to proteolytic degradation, binding to food compounds, and variation in the solubility of this bacteriocin, direct application of pediocin has been limited, especially in low concentration or during long-term storage at improper temperatures.

6. Body Systems and Health Areas

• Gastrointestinal system: As a homofermentative bacterium that can grow in a wide range of pH, temperature, and osmotic pressure, P. acidilactici is capable of colonizing the digestive tract. It is associated with probiotic modulation of the gut microbiome, pathogen exclusion, and intestinal barrier integrity.
• Immune system: P. acidilactici has drawn attention for its unique functional properties; it can produce bacteriocins, has immunomodulatory effects, and is capable of inhibiting pathogenic bacteria.
• Central nervous system / Gut-brain axis: Recent advances have further elucidated the specific mechanisms by which P. acidilactici modulates the gut-brain axis. Furthermore, it actively alters the intestinal metabolome by producing SCFAs and metabolizing tryptophan into neuroactive compounds like indole-3-lactic acid (ILA).
• Metabolic system: Findings support the possibility that P. acidilactici FZU106 has the potential to reduce the disturbance of lipid metabolism by regulating intestinal microflora and liver gene expression profiles.
• Female genitourinary system: Evidence from a multi-strain clinical trial suggests a role in restoring vaginal flora following treatment for bacterial vaginosis and vulvovaginal candidiasis (see Section 5.8).
• Detoxification/excretion: Preliminary human evidence (strain GR-1) suggests a role in reducing blood levels of occupational heavy metals via increased fecal excretion.

7. Dosage Forms and Doses Reported in Studies

Human Studies

• P. acidilactici PA53 was administered at 30 billion CFU/day (in maltodextrin) in an 8-week RCT enrolling 75 older adults (aged 55–70).
• In a 4-week randomized, placebo-controlled trial of P. acidilactici CCFM6432 in 39 patients with depressive disorder, the intervention and placebo groups each consisted of approximately 19–20 participants. The study was registered as ChiCTR2300071025.
• Healthy volunteers in a pilot study were randomly assigned two capsules of placebo or Pediococcus probiotics at 4 billion CFU daily for three months.
• An in vivo oral feeding study administered cells at an average dosage of 10⁸–10¹⁰ cells/mL/day to 10 healthy subjects in 1 mL buttermilk base, once a day for 4 weeks continuously.
• A vaginal capsule containing P. acidilactici LN23 and three other strains at a combined dose of 10⁸–10¹⁰ CFU was administered for 5 days post-conventional treatment in 95 women.
• Common supplemental human doses for probiotic preparations containing P. acidilactici range from 1 × 10⁸ to 1 × 10¹¹ CFU per day, depending on formulation and target population, and are very strain-specific.

Animal Studies (for Reference)

• C57BL/6 mice in a 12-week antidiabetic study were given 1 × 10¹⁰ CFU/day of pA1c, enriched in a high-fat diet.
• Mice in a colitis model received dietary supplementation containing P. acidilactici SK2 cells at a daily dose of 10⁹ CFU.
• Authorized dosages for zootechnical feed additive use are a minimum of 1 × 10⁹ CFU/kg feed or 5 × 10⁸ CFU/L water for poultry; 1 × 10⁹ CFU/kg feed for all porcine species, avian species, fish, and crustaceans.

8. Safety Considerations

Regulatory Status

Pediococcus acidilactici has been included on the European Food Safety Authority's (EFSA) list of Qualified Presumption of Safety (QPS) biological agents since the establishment of the QPS process in 2007, allowing its use in food and feed applications without case-by-case safety assessments for qualified strains. Specific strains, such as CNCM I-4622, have been authorized as a feed additive under EU Regulation (EC) No 1831/2003 for use in animal nutrition, including aquaculture, following EFSA safety evaluations.

In the United States, the FDA has granted Generally Recognized as Safe (GRAS) status to multiple strains of P. acidilactici for applications including antimicrobial control in meat products and as a probiotic ingredient in foods. Internationally, the Codex Alimentarius Commission recognizes lactic acid bacteria, including Pediococcus species, as safe starter cultures for fermented milk products under standards such as CXS 243-2003.

Opportunistic Infection Risk

From a medical point of view, pediococci are opportunistically pathogenic and can be associated with human infections when patients are debilitated as a result of trauma or underlying disease. Pediococci are recognized as potential human pathogens that may cause septic and gouty arthritis, especially in debilitated persons. Pediococcus acidilactici has caused septicemia in reported clinical cases, and P. pentosaceus has caused bacteremia in infants.

Antibiotic Resistance

Some strains of pediococci have acquired resistance towards antibiotics such as erythromycin, chloramphenicol, and aminoglycosides, indicating a potential for antibiotic resistance gene transfer. P. acidilactici HM3020 was inducibly resistant to macrolide, lincosamide, and streptogramin B-type (MLS) antibiotics. Resistance was due to a determinant homologous to ermAM and carried by a nontransferable 46-kb plasmid, pVM20.

P. acidilactici exhibits intrinsic resistance to certain antibiotics such as vancomycin, which is an inherent characteristic of the genus and not transferable. A 2025 safety assessment of strains SY21 and SY22 confirmed that antibiotic resistance exceeding EFSA cut-off values (kanamycin and clindamycin) was intrinsic, with no transferable resistance genes detected via whole-genome sequencing.

The importance of integrating genomic and phenotypic approaches in probiotic safety evaluations has been underscored by research. The presence of plasmid-borne antimicrobial resistance genes in certain strains advises caution in their use, impacting probiotic selection and regulatory compliance in agriculture.

The antibiotics most active against clinical Pediococcus isolates in susceptibility studies include penicillin G, imipenem, gentamicin, netilmicin, erythromycin, clindamycin, rifampin, chloramphenicol, daptomycin, and ramoplanin.

Hemolytic Activity and Virulence Factors

High-quality probiotic strains are non-hemolytic (gamma hemolytic). Strains P10 and SY21/SY22 show no lysis of red blood cells. Multiple whole-genome sequencing studies have confirmed the absence of transmissible antibiotic resistance genes and virulence factors in well-characterized strains, and regulatory bodies including EFSA have assigned QPS consideration to the species.

Strain Specificity as a Safety Consideration

Evidence for benefits is strain-specific: many industrial and animal studies show robust effects for growth, pathogen suppression, and food safety; human clinical evidence is emerging but heterogeneous. An exact identification of strains associated with infection, or of strains chosen for development of starter cultures or probiotics, is required and needs to be based on sound taxonomy.

Clinical trials including the 12-week human RCT on strain GR-1 reported no significant adverse events.

References

• Wikipedia — Pediococcus acidilactici
• PMC — Genomic Insight into Pediococcus acidilactici HN9, a Potential Probiotic Strain Isolated from the Traditional Thai-Style Fermented Beef Nhang
• PMC — Beneficial Features of Pediococcus: From Starter Cultures and Inhibitory Activities to Probiotic Benefits
• Springer — Probiotic and Functional Characterization of Pediococcus acidilactici Isolated from Bhaati Jaanr, Traditional Fermented Rice Porridge
• PMC — Draft Genome Sequencing of Pediococcus acidilactici Strains Isolated from Cow's Milk
• PMC — Comparative Genomic Analysis of the Pediococcus Genus Reveals Functional Diversity for Fermentation and Probiotic Applications
• PMC — Imaging Mass Spectrometry and Genome Mining Reveal Antimicrobial Peptides of Novel Pediococcus acidilactici CCFM18
• PMC — Pediocin PA-1, a Bacteriocin from Pediococcus acidilactici PAC1.0, Forms Hydrophilic Pores in the Cytoplasmic Membrane of Target Cells
• PMC — Synthesis, Antimicrobial Activity and Conformational Analysis of the Class IIa Bacteriocin Pediocin PA-1 and Analogs Thereof
• PMC — Antibacterial Activity of Pediocin and Pediocin-Producing Bacteria Against Listeria monocytogenes in Meat Products
• PMC — In Vitro and In Vivo Survival and Colonic Adhesion of Pediococcus acidilactici MTCC5101 in Human Gut
• PMC — Evaluation of the Clinical Efficacy of Pediococcus acidilactici CCFM6432 in Alleviating Depression
• PubMed — Pediococcus acidilactici PA53 Improves Emotional Well-Being and Gut Health while Modulating Microbiota Composition in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial
• PMC — Pediococcus acidilactici FZU106 Alleviates High-Fat Diet-Induced Lipid Metabolism Disorder in Association with the Modulation of Intestinal Microbiota in Hyperlipidemic Rats
• PMC — Pediococcus acidilactici CECT9879 (pA1c) Counteracts the Effect of a High-Glucose Exposure in C. elegans by Affecting the Insulin Signaling Pathway (IIS)
• PMC — Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice
• PMC — Pediococcus acidilactici pA1c® Improves the Beneficial Effects of Metformin Treatment in Type 2 Diabetes by Controlling Glycaemia and Modulating Intestinal Microbiota
• PubMed — Pediococcus acidilactici CECT 9879 (pA1c®) and Heat Inactivated pA1c® Ameliorate Gestational Diabetes Mellitus in Mice
• PMC — Pediococcus Acidilactici NRRL B-50517 as a Safe Probiotic for Regulation of Weight Related Pro-inflammatory Cytokines: A Double-blind Placebo-controlled Pilot Study
• PMC — Antimicrobial Susceptibility of Pediococcus spp. and Genetic Basis of Macrolide Resistance in Pediococcus acidilactici HM3020
• PMC — Integrative Genomic Characterization of Five Pediococcus acidilactici Strains Reveals Differing Probiotic Safety Profiles
• PMC — Lactiplantibacillus paraplantarum BPF2 and Pediococcus acidilactici ST6, Two Bacteriocinogenic Isolated Strains from Andalusian Spontaneous Fermented Sausages
• PMC — Evaluation of Pediococcus acidilactici AS185 as an Adjunct Culture in Probiotic Cheddar Cheese Manufacture
• PMC — Pediococcus acidilactici P25 Protected Caenorhabditis elegans against Enterotoxigenic Escherichia coli K88 Infection and Transcriptomic Analysis of Its Potential Mechanisms
• ScienceDirect — Dietary Supplementation with a Novel Wild-Type Pediococcus acidilactici Strain Suppresses Inflammation and Modulates the Gut Microbiome in a Mouse Model of Colitis
• Wiley — Bacteriocins: Properties and Potential Use as Antimicrobials
• Frontiers in Microbiology — Impact of Pediococcus acidilactici GLP06 Supplementation on Gut Microbes and Metabolites in Adult Beagles: A Comparative Analysis
• ResearchGate — Pediococcus acidilactici CCFM6432 Alleviates Anhedonia in Major Depression through Immune-Inflammatory Modulation: An Extended Trial Analysis