IngredientsPropionibacterium shermanii is the historical and commercially persistent name for what modern taxonomy now recognizes as a subspecies of Propionibacterium freudenreichii. According to Scholz and Kilian (2016), Propionibacterium shermanii is a later heterotypic synonym of Propionibacterium freudenreichii van Niel 1928. The name "P. shermanii" was originally published by van Niel in 1928, and for most of the twentieth century it was used interchangeably with the subspecific designation Propionibacterium freudenreichii subsp. shermanii.
The distinction between the two subspecies — Propionibacterium freudenreichii subsp. freudenreichii and subsp. shermanii — has been considered taxonomically irrelevant. The only difference between these subspecies was whether they had the ability to reduce nitrate (subsp. freudenreichii) or ferment lactose (subsp. shermanii). Because these phenotypic traits are not genetically coupled, they had to be classified as separate phenotypes.
To re-evaluate the taxonomy of the family and to elucidate the interspecies relatedness, Scholz and Kilian (2016) compared 162 public whole-genome sequences of strains representing species of the family Propionibacteriaceae. They found substantial discrepancies between the phylogenetic signals of 16S rRNA gene sequence analysis and their high-resolution core-genome analysis. To accommodate these discrepancies, they proposed three novel genera: Acidipropionibacterium gen. nov., Cutibacterium gen. nov., and Pseudopropionibacterium gen. nov.
In current scientific literature, the organism is most accurately designated as Propionibacterium freudenreichii subsp. shermanii, though the name P. shermanii continues to appear in older literature, food science, commercial starter culture labeling, and some supplement contexts. Throughout this article, both the historical name and the current accepted name are used interchangeably, as the science being discussed applies to the same organism.
Propionibacterium freudenreichii is a neutral pH, non-motile, and non-spore-forming gram-positive rod. It is a classical dairy propionibacterium that is distinct from the opportunistic pathogen Propionibacterium acnes, which belongs to the cutaneous propionibacteria. Propionibacteria are pleomorphic rods, often diphtheroid or club-shaped, but may also exist as single cells, as pairs, or branched; these are anaerobic to aerotolerant and generally catalase-positive.
Propionibacterium is a gram-positive, anaerobic, rod-shaped genus of bacteria named for their unique metabolism: they are able to synthesize propionic acid by using unusual transcarboxylase enzymes. The organism exhibits slow growth with a generation time of approximately 5 hours, has low nutritional requirements, and demonstrates tolerance to various environmental stresses, including those in the digestive tract.
P. freudenreichii has a circular chromosome about 2.5 Mb long. It is primarily isolated from dairy sources such as Emmental cheese, and naturally inhabits environments like milk, silage, soil, the rumen of ruminants, and the human colon.
Propionibacterium freudenreichii is a generally recognized as safe (GRAS) bacterium with the ability to produce active vitamin B12 in different plant-based matrices. In contrast to Pseudomonas denitrificans, it is a Generally Recognized As Safe (GRAS) microorganism and has the Qualified Presumption of Safety (QPS) status granted by the EFSA.
Propionibacterium freudenreichii is widely used in the food industry, especially as a starter in the production of Swiss-type cheeses such as Emmental and Maasdam. These bacteria are essential for the development of a nutty and sweet flavor. They also produce CO₂ responsible for the appearance of the holes typical of Swiss cheeses. An estimated one billion living cells of P. freudenreichii are present in one gram of Emmental.
In the context of dietary supplements and functional foods, P. shermanii / P. freudenreichii subsp. shermanii is encountered in several forms:
Propionibacterium freudenreichii was first discovered and isolated in the early 20th century by Eduard von Freudenreich and Sigurd Orla-Jensen. They discovered the bacterium while studying propionic acid fermentation in Emmental cheese. P. freudenreichii was first described more than one century ago in Swiss Emmental cheese by Orla Jensen and von Freudenreich (1906), who showed the relationship between the presence of these bacteria producing propionic acid and the formation of the characteristic round holes (eyes) in cheese.
Propionibacterium freudenreichii was first adopted in the early 20th century as a starter culture in Swiss-type cheese production, particularly for Emmental, to promote consistent ripening, flavor development through propionate and acetate production, and eye formation via carbon dioxide generation. It is widely used as a ripening culture in the manufacture of Swiss-type cheeses.
The subspecies designation shermanii was introduced by van Niel in 1928, reflecting the organism isolated from Emmental and related Swiss-type cheeses that could ferment lactose — a property which became important in the cheesemaking industry for regulating the rate of fermentation.
When Emmental cheese is being produced, P. freudenreichii ferments lactate to form acetate, propionate, and carbon dioxide: (3 C₃H₆O₃ → 2 C₂H₅CO₂⁻ + C₂H₃O₂⁻ + CO₂). The products of this fermentation contribute to the nutty and sweet flavors of the cheese, and the carbon dioxide byproduct is responsible for forming the holes, or "eyes," in the cheese. Cheesemakers control the size of the holes by changing the acidity, temperature, and curing time of the mixture.
Propionibacterium freudenreichii subsp. shermanii seems to be the species that is most resistant to both cold and heat stresses, which may partially explain why it is found mainly in Swiss-type cheeses such as Emmental, where the technology involves hot and cold stages.
The long-standing use of P. freudenreichii subsp. shermanii in Swiss cheese production constitutes what regulators now recognize as a centuries-long record of safe human consumption via fermented dairy foods. Its use in food fermentation dates back over a century, establishing a strong historical precedent for its safety and palatability in human diets.
Formal documentation of P. shermanii as a deliberately applied medicinal agent is limited, as its identity within traditionally consumed fermented dairy foods was not scientifically established until the 20th century. Dairy propionibacteria are Actinobacteria, mainly isolated from dairy environments. Propionibacterium freudenreichii has been used for a long time as a ripening culture in Swiss-type cheese manufacture, and is more and more considered for its potent probiotic effects. The use of fermented whey and cultured dairy products in Central European folk medicine predates the microbiological characterization of their constituent organisms.
Early supplement applications emerged in the late 20th century. It is a long known fact that propionic acid inhibits yeast and molds. Propionic acid is produced by harmless Propionibacterium shermanii or by several species of Propionibacterium by using either glucose, lactose, or lactic acid as a substrate. The Propionibacterium can thus reduce lactate or lactic acid to propionic acid and carbon dioxide, which can retard the growth of yeasts and molds. In addition, propionic acid bacterium can synthesize B-vitamins in the human gastrointestinal tract. These properties were recognized as the basis for early probiotic supplement preparations combining P. shermanii with dietary fiber and other beneficial organisms.
Propionibacteria have a peculiar metabolism, characterised by the formation of propionic acid as main fermentation end-product. They have few nutritional requirements and are able to use a variety of carbon substrates. The principal bioactive metabolites of P. shermanii / P. freudenreichii are:
From the sequence of P. freudenreichii CIRM-BIA1T genome, many pathways were reconstituted, including the Wood–Werkman cycle, enzymes of the respiratory chain, synthesis pathways for all amino acids and many vitamins including vitamin B12. The key feature of the Wood-Werkman cycle in P. freudenreichii is a transcarboxylation reaction without the involvement of free CO₂. The enzyme catalyzing this reaction is a methylmalonyl-CoA carboxytransferase, transferring a carboxyl group from methylmalonyl-CoA to pyruvate to form oxaloacetate and propionyl-CoA. The enzyme involved has been fully characterized and its structure resolved. It is a biotin-dependent carboxytransferase (EC 2.1.3.1) composed of three subunits.
The bifidogenic growth stimulator (BGS) selectively stimulates the growth of Bifidobacteria through the action of its component 1,4-dihydroxy-2-naphthoic acid that is produced by Propionibacterium freudenreichii ET-3 isolated from Swiss cheese. The 1,4-dihydroxy-2-naphthoic acid component has growth stimulatory activity for Bifidobacteria at an extremely low concentration in vitro. This bifidogenic mechanism operates through the NAD(P)H diaphorase/peroxidase redox system in bifidobacteria.
Consumption of P. freudenreichii modulates the gut microbiota, which makes it both probiotic and prebiotic. The probiotic efficacy of propionibacteria was species- and strain-dependent. Two of the strains, namely TL133 and TL1348, altered the faecal microbiota composition, with TL133 also increasing the caecal concentration of acetate, propionate and butyrate.
The mRNA and protein expression levels of MUC2, a main component of intestinal mucus, increased in cells treated with P. freudenreichii culture supernatant. The culture supernatant and live P. freudenreichii reduced the disease activity index (DAI) in rats with DSS-induced colitis. After treatment, the mRNA levels of typical pro-inflammatory cytokines decreased and the inflammatory state was histologically improved.
The anti-inflammatory effect was suggested in IBD patients and confirmed in animal colitis models. Immunomodulatory properties are due to several metabolites as SCFAs and to cell wall components. Surface proteins are involved in adhesion and immunostimulation by P. freudenreichii.
Short-chain fatty acids are known to specifically induce apoptosis of cancer cells. Food grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via the production and release of SCFA (propionate and acetate) acting on mitochondria. As demonstrated for butyrate, the anti-cancerous effect of propionibacterial SCFA consists in inducing apoptosis. The apoptotic intrinsic pathway is activated: SCFAs act on the mitochondria adenine nucleotide translocator (ANT) pore, causing mitochondria depolarization and permeabilisation, leakage of cytochrome C, and caspase activation.
Glycolysis, the Wood-Werkman cycle and the oxidative phosphorylation pathways were down-regulated in the colon environment, but induction of specific carbohydrate catabolisms and alternative pathways were induced to produce NADH, NADPH, ATP and precursors. Genes involved in stress response were down-regulated and genes specifically expressed during cell division were induced, suggesting that P. freudenreichii adapted its metabolism to the conditions encountered in the colon.
The fermentation of several dietary substrates by P. shermanii can improve nutrient bioavailability. P. shermanii generates enzymes during fermentation that aid in the breakdown of complex nutrients, facilitating easier absorption and utilization by the body.
Evidence level: Human studies available; moderate evidence for bifidogenic effect in healthy volunteers.
Propionibacterium freudenreichii stimulated the growth of Bifidobacteria in the colon in healthy volunteers. In addition to their use in cheese technology, dairy propionibacteria have been identified as potential probiotics. However, to have a probiotic effect, propionibacteria have to survive and to remain metabolically active in the digestive tract. Survival and metabolic activity of P. freudenreichii within the gastrointestinal tract of human microbiota-associated rats has been investigated, alongside its influence on intestinal microbiota composition and metabolism.
Twenty-five dairy Propionibacterium strains were screened for their tolerance towards digestive stresses and their ability to produce propionate in a medium mimicking the content of the human colon. Three strains were selected and a daily dose of 2 × 10¹⁰ colony-forming units was fed to groups of human microbiota-associated rats for 20 days before microbiological, biochemical, and molecular investigations were carried out. These strains all reached 8-log values per g faeces, showing their ability to survive in the gastrointestinal tract. Transcriptional activity within the intestine was demonstrated by the presence of P. freudenreichii-specific transcarboxylase mRNA.
Limitation: The animal model used (human microbiota-associated rats) is more informative than standard rodent models but is not equivalent to direct human trials. Human clinical data on microbiota modulation are from small studies.
Evidence level: Preliminary human pilot data; animal and in vitro data supportive but not definitive.
This study investigated the efficacy and safety of BGS in the treatment of ulcerative colitis. Twelve patients with mildly to moderately active ulcerative colitis received orally 4.5 g of BGS daily for 4 weeks in an open-label treatment protocol while baseline anti-inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Concentrations of short-chain fatty acids and the composition of commensal bacteria, including Bifidobacteria, Enterobacteria, and Bacteroides species, were studied in stool samples.
Propionibacterium freudenreichii improved the symptoms of mild to moderate ulcerative colitis in this human pilot study. In animal models, 1,4-dihydroxy-2-naphthoic acid (DHNA), a bifidogenic growth stimulator from Propionibacterium freudenreichii, is thought to have a beneficial effect as a prebiotic, and researchers investigated its in vivo effect on intestinal inflammation. Colitis was induced in mice by treatment with 2.0% DSS for seven days. DHNA (0.6 or 2.0 mg/kg) was given in drinking water prior to (preventive study) or after (therapeutic study) DSS administration.
Some strains are also used as probiotics because they produce bifidogenic compounds, they are resistant to digestive stress, and they may be endowed with anti-inflammatory capabilities and could be used to prevent inflammatory bowel diseases.
Limitation: The human UC pilot study (n=12) was open-label, uncontrolled, and used a whey-derived cell-free preparation (BGS) rather than live bacteria. This severely limits conclusions about efficacy. Controlled clinical trials are needed.
Evidence level: Single small human trial; insufficient to establish a clinical claim.
Propionibacterium freudenreichii relieved constipation in 41 healthy young women. This finding comes from a single small study and has not been replicated in larger controlled trials. The specific preparation, dose, and duration used in this study are not fully characterized in the available published literature.
Evidence level: Well-established at the biosynthetic/microbiological level; human nutritional impact being actively investigated.
Cobalamin, generally known as vitamin B12, is a crucial component required for humans in several physiological processes. It has been produced from sources that are derived from animals, making it difficult for vegetarians and vegans to consume the recommended amount each day. The importance of vitamin B12 in red blood cell production, DNA synthesis, and brain processes has been highlighted.
Propionibacterium shermanii and Pseudomonas denitrificans have demonstrated remarkable potential as fermented sources of vitamin B12. Compared to conventional sources, the bioavailability of vitamin B12 produced by P. denitrificans and P. shermanii is more effective in meeting dietary needs.
In a demonstration of industrial-scale potential, vitamin B12 level reached 357 ± 8 ng/g dry weight after 1 day of pH-controlled fermentation with P. freudenreichii monoculture and remained stable thereafter. In co-fermentation with L. brevis, slightly less vitamin B12 (255 ± 31 ng/g dw) was produced in 1 day. On day 3, vitamin B12 content in pH-controlled co-fermentation increased to 332 ± 44 ng/g dw.
Vitamin B12 is a widely used compound in the feed and food, healthcare, and medical industries that can only be produced by fermentation because of the complexity of its chemical synthesis. Industrial vitamin B12 production with Pseudomonas denitrificans strains has been favored due to their faster growth rate and productivity, displacing other traditionally employed anaerobic strains such as Propionibacterium freudenreichii. However, P. freudenreichii still presents properties that make it an interesting candidate for cobalamin production.
Limitation: Most evidence for vitamin B12 production is derived from in vitro fermentation experiments and food fortification studies. Direct human trials confirming that consuming P. shermanii-fermented foods meaningfully improves cobalamin status are limited.
Evidence level: In vitro and animal data only. No human clinical evidence. Results should be interpreted with extreme caution.
Propionibacterium freudenreichii subsp. shermanii has been shown to possess the ability to induce apoptosis in colorectal and gastric cancer cells in vitro (HT29, Caco2, and HGT-1 cancerous cell lines) and in vivo within human microbiota-associated rats. Propionate and acetate, produced by dairy propionibacteria, were identified as the main actors of this effect.
Several studies have demonstrated that P. freudenreichii exhibits inhibitory effects on various colon carcinoma cell lines, including HT29, HeLa, and CaCo-2 cells. Notably, P. freudenreichii does not display cytotoxicity or inhibit the proliferation of normal colon cells, such as Human Epithelial Intestinal Cells (HIEC).
The pro-apoptotic potential of fermented milk exclusively fermented by P. freudenreichii was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest, phosphatidylserine exposure, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation, and cytochrome c release. Remarkably, this new fermented milk enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy.
An animal experiment was performed using four groups of SD rats: normal control, AOM group, PF group (1 × 10⁹ CFU/mL), and standard drug control (5-fluorouracil, 35 mg/kg). Methylene blue staining of colon tissues showed that the administration of PF significantly reduced the formation of colonic aberrant crypt foci (ACF) compared to the AOM control group.
Clinical studies are lacking, and it is unclear whether these studies will be at all relevant to human cancers.
Evidence level: Murine model only.
Promising results suggest that immunomodulatory probiotic bacteria, in particular, may yield new biotherapeutic or preventive strategies to address the increasing burden of food allergies. Researchers investigated the potential impact of Propionibacterium freudenreichii CIRM-BIA129, a recognized immunomodulatory probiotic bacterium, on food allergy development in a murine model. Preventive effects of this probiotic were evaluated in the context of an induced wheat gliadin allergy. Results were promising in the mouse model, but no human studies have been conducted.
Evidence level: In vitro only.
Propionibacterium freudenreichii binds cadmium and lead efficiently at low concentration ranges commonly observed in foods. This finding is preliminary and limited to in vitro conditions.
Based on the totality of available scientific evidence, P. shermanii / P. freudenreichii subsp. shermanii is associated with the following body systems and health areas:
The following dosages appear in the peer-reviewed and toxicological literature. These are reported descriptively, as they appeared in source studies, and are not recommendations.
No standardized therapeutic dosage for P. shermanii preparations has been established in human clinical guidelines. Robust clinical trials in humans remain limited, and definitive health outcomes have yet to be conclusively demonstrated.
P. freudenreichii is considered "generally recognized as safe" (GRAS) by the US Food and Drug Administration (USFDA), and its safety for human consumption has been evaluated by some studies, with no adverse effects reported. Propionibacterium freudenreichii is an industrially important bacterium granted the Generally Recognized as Safe (GRAS) status, due to its long safe use in food bioprocesses.
Propionibacterium freudenreichii ET-3 culture, a cell-free product of whey fermentation, has been shown to promote the growth of Bifidobacteria through the action of DHNA, and has potential use in the food and supplement industries. Although currently used as a food ingredient in Japan, the safety of this novel ingredient had not been previously evaluated through traditional toxicity testing. In a 4-week oral toxicity study, administration of 6000 mg/kg body weight/day P. freudenreichii ET-3 culture was without compound-related adverse effects on clinical signs, body weights, food consumption, ophthalmology, hematology, clinical chemistry, urinalysis, organ weights, and gross and microscopic findings in male and female Sprague-Dawley rats.
In vitro mutagenicity testing demonstrated that P. freudenreichii ET-3 culture was non-mutagenic in the bacterial reverse mutation assay using a standard battery of bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, and TA1537 and Escherichia coli WP2 uvrA) and non-clastogenic in Chinese hamster lung cells in the mammalian chromosome aberration test. Together, the results of these studies support the safety of P. freudenreichii ET-3 culture for use in foods for human consumption.
In the human clinical safety studies, there were no statistically significant differences between the placebo and active (P. freudenreichii ET-3 culture medium) supplementation periods in any measured parameter. In addition, there were no statistically significant differences between the placebo and active groups at baseline. The clinical safety of P. freudenreichii ET-3 culture medium was reported following short-term intakes of excessively high doses (3 g P. freudenreichii ET-3 culture medium or 283.5 μg of DHNA per day, which is 15 times the recommended intake) and long-term (13-week) ingestion of high doses (0.267 mg P. freudenreichii ET-3 culture medium or 22.5 μg of DHNA, which is three times the recommended intake).
P. freudenreichii has an intrinsic resistance to several antibiotics, including aminoglycosides, first- and second-generation quinolones, oxacillin, metronidazole, kanamycin, and levofloxacin. This resistance is not encoded by bacterial plasmids, and no transferable antibiotic resistance has been recorded. The absence of transferable antibiotic resistance genes is a significant safety feature for probiotic applications, as it means the organism does not pose a risk of spreading resistance to pathogenic bacteria.
P. freudenreichii revealed an immunomodulatory effect confirmed in vivo by the ability to protect mice from induced acute colitis. This effect is, however, highly strain-dependent. This effect is, however, highly strain-dependent, meaning that safety and efficacy findings from one strain or preparation cannot be assumed to apply to all commercially available P. shermanii / P. freudenreichii products.
Propionibacterium freudenreichii is an actinobacterium widely used in dairy industry during the ripening process of Swiss-type cheeses and which presents probiotic properties. P. freudenreichii is reportedly a hardy bacterium, able to survive during the cheese-making process and when subjected to digestive stresses. P. freudenreichii can stay alive and metabolically active for long periods even under stressful conditions like the gastro-intestinal tract environment or in cold conditions.
Propionibacterium freudenreichii is a neutral pH, non-motile, and non-spore-forming gram-positive rod. It is a classical dairy propionibacterium that is distinct from the opportunistic pathogen Propionibacterium acnes, which belongs to the cutaneous propionibacteria. The GRAS status and long history of safe human consumption through Emmental and related cheeses clearly distinguishes this organism from its pathogenic relatives in the genus.
P. shermanii / P. freudenreichii subsp. shermanii is among the better-characterized dairy probiotic organisms at the mechanistic and preclinical level. The probiotic properties of dairy propionibacteria are strain-dependent and include microbiota modulation, apoptosis modulation in colonic cells, and immunomodulation. Some of these probiotic abilities were validated at the clinical level. However, the extent of this clinical validation is limited:
P. freudenreichii can exert health-promoting activities, such as a bifidogenic effect in the human gut and promising immunomodulatory effects. The organism's GRAS and QPS status, combined with a long history of safe consumption in fermented foods and formally negative genotoxicity and toxicology studies, supports its safety for use in dietary supplements. Its efficacy for specific health claims, however, awaits further clinical substantiation.
Health conditions that Propionibacterium shermanii may help support.
Body systems that Propionibacterium shermanii may help support.
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