Proteins from P. freudenreichii related to its immunomodulatory properties.
Propionibacterium freudenreichii is a Gram-positive dairy probiotic bacterial species that has been used as a ripening starter in the production of Swiss-type cheese for a long time. It has been exploited for the optimization of cheese production, including ripening capacities and aroma compounds production, but also for the production of vitamin B12 and organic acids. Furthermore, it has emerged in the probiotics landscape owing to several beneficial traits, including tolerance to stress in the gastrointestinal tract, adhesion to host cells, anti-pathogenic activity, anticancer potential and immunomodulatory properties. These beneficial properties have been confirmed with in vitro and in vivo investigations, using several omics approaches that allowed the identification of important molecular actors, such as surface proteins, short-chain fatty acids and bifidogenic factors. The diversity within the species was shown to be an important aspect to take into consideration, since many of these properties were strain-dependent. New studies should dive further into the molecular mechanisms related to the beneficial properties of this species and of its products, while considering the complexities of strain diversity and the interactions with the host and its microbiota. This chapter reviews current knowledge on the possible impact of P. freudenreichii on human health.
- Propionibacterium freudenreichii
- food microbiology
The denomination “probiotics” comprises living microorganisms, including bacteria and yeasts, with health-promoting properties and suitable for safe consumption, as confirmed by their dietary uses for thousands of years of human history [1, 2, 3]. Lactic acid bacteria and bifidobacteria comprise traditional probiotic bacteria species, widely documented and commercialized [3, 4]. However, different species have emerged in the probiotics landscape, such as the dairy species
2. Technological importance
This bacterium is also well recognized to encompass a pathway for vitamin B12 (cobalamin) synthesis [8, 9]. Vitamin B12 is a water-soluble vitamin, which plays a key role in the functioning of the brain, of the nervous system and in the production of blood . It is also a co-factor of methylmalonyl-CoA mutase, which catalyzes a crucial step in the fermentative route to produce propionate . Therefore, the growth conditions of
The production of vitamin B12, organic acids, trehalose and other metabolites, together with the safe use as cheese ripening starter and probiotic characteristics, make this bacterium attractive for several biotechnological and industrial applications [5, 6, 29, 30]. A wide range of genetic and environmental optimizations have been conducted to improve these properties [6, 29]. Moreover, some optimizations of the growth and processing conditions allowed the improvement of resistance towards storage and towards several industrial processes, such as freeze-drying and spray-drying [30, 31, 32, 33].
3. Strain variability
The interesting properties of this bacterium, such as health-promoting features, and participation to industrial vitamin B12 and cheese production, were shown to be strain-dependent, suggesting the need for analysis that account for that variability . As an example, some strains presented differences in nitrogen and sugar degradation, which had a genetic origin, probably resulting from horizontal transfers, duplications, transpositions and other mutations . This strain diversity was confirmed at the genomic level by another study and attributed to transposable elements, in such a way that genome plasticity enabled bacterial adaptation to several environments .
In view of this strain-related variability, there have been efforts to specify criteria for the selection of probiotic strains. These criteria include tolerance to stresses encountered within the gastrointestinal tract, adhesion to host cells, anti-pathogenic activity, anticancer potential, immunomodulatory properties, industrial requirements and molecular characterization using omics methodologies . Mounting evidence shows that
4. Stress tolerance
Regarding stress tolerance and adaptation to the gastrointestinal tract (GIT), some
Moreover, this resistance was also evidenced
Other aspects of
Another important feature of
5. Adhesion properties
Adhesion to host cells is another important feature of probiotics, which favors their local beneficial action. Early studies revealed the ability of several probiotic bacteria, including
6. Anti-pathogenic activity
There are also several evidences of an anti-pathogenic activity in this species.
In line with the synergies observed in terms of adhesion, probiotic combinations were proposed to improve anti-pathogenic activity, such as a combination of
7. Anticancer potential
Promising results, in the context of intestinal carcinogenesis, were also reported in this species. A pioneer study showed that
8. Modulation of microbiota composition
Regarding the modulation of microbiota composition, consumption of dairy propionibacteria was shown to enhance intestinal populations of bifidobacteria in humans [67, 68]. In line with this, the stimulation of bifidogenic growth was observed in cell-free filtrate and cellular methanol extract derived from
The bifidogenic growth stimulator derived from
9. Immunomodulatory properties
There is mounting evidence, both
The roles of
Regarding the bacterial factors involved in immunomodulation, evidence points out mainly to surface proteins (Table 1). The strain
|CIRM-BIA129 (ITG P20)||Ensemble of surface proteins||proteomic, |||
|GroL2||60 kDa chaperonin 2||CDP49125||genomic, proteomic|||
|HsdM3||Type I restriction-modification system DNA methylase||CDP48267||genomic, transcriptomic, mutant studies |||
|Lacl1||Arabinose operon repressor||CDP47860||transcriptomic|||
|MerA||Pyridine nucleotide-disulphide oxidoreductase||CDP48574||genomic, proteomic|||
|Pep||Hypothetical protein||CDP48241||genomic, mutant studies |||
|PFCIRM129_04790||Hypothetical protein||CDP48736||genomic, transcriptomic|||
|PFCIRM129_10930||Hypothetical protein||CDP48242||genomic, transcriptomic|||
|SlpB||Surface layer protein B||CDP48273||genomic, transcriptomic, proteomic, mutant studies |||
|mutant studies |||
|mutant studies |||
|SlpE||Surface protein with SLH domain||CDP48858||genomic, transcriptomic, proteomic, mutant studies |||
|SlpF||Surface protein with SLH domain||CDP49687||proteomic, mutant studies |||
|CIRM-BIA 121||Acn||Aconitase, Aconitate hydratase||CEG89374||transcriptomic|||
|Eno1||Enolase 1||CEG91483||proteomic, mutant studies |||
|HtrA4||Serine protease||CEG91080||genomic, transcriptomic, proteomic, mutant studies |||
|PFCIRM121_08235||Hypothetical protein/unknown function||CEG91253||genomic, mutant studies |||
|SlpC1||Surface layer protein C||CEG91216||genomic, transcriptomic|||
|UF1||LspA||Large surface layer protein A||n.a.||proteomic, |||
|DlaT||Dihydrolipoamide acetyltransferase||n.a.||proteomic, mutant studies |||
In addition to surface proteins, DHNA was also associated to immunomodulation. Beside its bifidogenic properties, DHNA inhibited the production of proinflammatory cytokines in intestinal macrophages of IL-10(−/−) mice treated with piroxicam . Moreover, DHNA was also described as an activator of aryl hydrocarbon receptor (AhR), which is involved in the detoxification of xenobiotics and inflammation regulation [87, 88].
10. Functional foods
Importantly, the immunomodulatory properties of
11. Safety assessments
The long history of safe production of fermented food, such as Emmental cheese, and the bacterium status of “generally recognized as safe” (GRAS) and “qualified presumption of safety” (QPS) assure the safety of
Moreover, several clinical trials tested multispecies probiotic supplementation containing propionibacteria. A complex formula that included
Importantly, probiotics supplementation is not recommended in cases of immunosuppression, such as during anticancer treatment . Moreover, their beneficial effects and safety are conditioned to a complex interplay between peculiarities of the host and of the probiotic strain or strains, which both encourages further research and suggests caution in some of its applications .
12. Postbiotics and beyond
As previously detailed,
In the case of
Postbiotics hold promising perspectives for developing novel probiotic-derived products with enhanced safety and functionality . Moreover, yield and cargo loading optimization are promising for modulating their properties, enhancing their beneficial effect and biotechnological applications . Finally, clinical trials should be conducted in the near future to assure the suitability of postbiotics and probiotics for therapy and prophylaxis, since they might exert a great impact in human health [93, 107, 109].
Overall, research on
We are thankful to Houyem Rabah, who kindly supplied a photography of an Emmental cheese. We are also thankful to the financial support from INRAE (Rennes, France) and Institut Agro (Rennes, France). VRR was supported by the International Cooperation Program CAPES/COFECUB at the Federal University of Minas Gerais funded by CAPES – the Brazilian Federal Agency for the Support and Evaluation of Graduate Education of the Brazilian Ministry of Education (number 99999.000058/2017-2103).
Conflict of interest
The authors declare no conflict of interest.
Ozen M, Dinleyici EC. The history of probiotics: The untold story. Benef Microbes 2015; 6: 159-165.
Gasbarrini G, Bonvicini F, Gramenzi A. Probiotics History. J Clin Gastroenterol 2016; 50: S116–S119.
de Melo Pereira GV, de Oliveira Coelho B, Magalhães Júnior AI, et al. How to select a probiotic? A review and update of methods and criteria. Biotechnology Advances 2018; 36: 2060-2076.
Douillard FP, de Vos WM. Biotechnology of health-promoting bacteria. Biotechnology Advances; 37. Epub ahead of print 1 November 2019. DOI: 10.1016/j.biotechadv.2019.03.008.
Rabah H, Rosa do Carmo F, Jan G. Dairy Propionibacteria: Versatile Probiotics. Microorganisms2017; 5: 24.
Piwowarek K, Lipińska E, Hać-Szymańczuk E, et al. Propionibacterium spp.-source of propionic acid, vitamin B12, and other metabolites important for the industry. Appl Microbiol Biotechnol 2018; 102: 515-538.
Scholz CFP, Kilian M. The natural history of cutaneous propionibacteria, and reclassification of selected species within the genus Propionibacterium to the proposed novel genera Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov. Int J Syst Evol Microbiol 2016; 66: 4422-4432.
Falentin H, Deutsch SM, Jan G, et al. The complete genome of propionibacterium freudenreichii CIRM-BIA1T, a hardy actinobacterium with food and probiotic applications. PLoS One; 5. Epub ahead of print 2010. DOI: 10.1371/journal.pone.0011748.
Thierry A, Deutsch SM, Falentin H, et al. New insights into physiology and metabolism of Propionibacterium freudenreichii. International Journal of Food Microbiology 2011; 149: 19-27.
Von Freudenreichii E, Orla-Jensen O. Uber die in Emmentalerkäse stattfindene Propionsäure-gärung. Zentralbl Bakteriol 1906; 17: 529-546.
Colliou N, Ge Y, Sahay B, et al. Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation. J Clin Invest 2017; 127: 3970-3986.
Ojala T, Laine PKS, Ahlroos T, et al. Functional genomics provides insights into the role of Propionibacterium freudenreichii ssp. shermanii JS in cheese ripening. Int J Food Microbiol 2017; 241: 39-48.
Loux V, Mariadassou M, Almeida S, et al. Mutations and genomic islands can explain the strain dependency of sugar utilization in 21 strains of Propionibacterium freudenreichii. BMC Genomics 2015; 16: 296.
Deborde C, Boyaval P. Interactions between Pyruvate and Lactate Metabolism in Propionibacterium freudenreichii subsp.shermanii: In Vivo 13C Nuclear Magnetic Resonance Studies. Appl Environ Microbiol 2000; 66: 2012-2020.
Gagnaire V, Jardin J, Rabah H, et al. Emmental Cheese Environment Enhances Propionibacterium freudenreichii Stress Tolerance. PLoS One 2015; 10: e0135780.
Poonam, Pophaly SD, Tomar SK, et al. Multifaceted attributes of dairy propionibacteria: A review. World Journal of Microbiology and Biotechnology 2012; 28: 3081-3095.
Abeijón Mukdsi MC, Falentin H, Maillard MB, et al. The Secreted Esterase of Propionibacterium freudenreichii Has a Major Role in Cheese Lipolysis. Appl Environ Microbiol 2014; 80: 751-756.
Rabah H, do Carmo FLR, Carvalho RD de O, et al. Beneficial propionibacteria within a probiotic emmental cheese: Impact on dextran sodium sulphate-induced colitis in mice. Microorganisms; 8. Epub ahead of print 1 March 2020. DOI: 10.3390/microorganisms8030380.
Rabah H, Ferret-Bernard S, Huang S, et al. The Cheese Matrix Modulates the Immunomodulatory Properties of Propionibacterium freudenreichii CIRM-BIA 129 in Healthy Piglets. Front Microbiol 2018; 9: 2584.
Plé C, Breton J, Richoux R, et al. Combining selected immunomodulatory Propionibacterium freudenreichii and Lactobacillus delbrueckii strains: Reverse engineering development of an anti-inflammatory cheese. Mol Nutr Food Res 2016; 60: 935-948.
Calderón-Ospina CA, Nava-Mesa MO. B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neurosci Ther 2020; 26: 5-13.
Takahashi-Iñiguez T, García-Hernandez E, Arreguín-Espinosa R, et al. Role of Vitamin B12 on methylmalonyl-CoA mutase activity. Journal of Zhejiang University: Science B 2012; 13: 423-437.
Chamlagain B, Sugito TA, Deptula P, et al. In situ production of active vitamin B12 in cereal matrices using Propionibacterium freudenreichii. Food Sci Nutr 2018; 6: 67-76.
Wang P, Shen C, Li L, et al. Simultaneous production of propionic acid and vitamin B12 from corn stalk hydrolysates by Propionibacterium freudenreichii in an expanded bed adsorption bioreactor. Prep Biochem Biotechnol 2020; 50: 763-767.
Hajfarajollah H, Mokhtarani B, Mortaheb H, et al. Vitamin B12 biosynthesis over waste frying sunflower oil as a cost effective and renewable substrate. J Food Sci Technol 2015; 52: 3273-3282.
Yu Y, Zhu X, Shen Y, et al. Enhancing the vitamin B12 production and growth of Propionibacterium freudenreichii in tofu wastewater via a light-induced vitamin B12 riboswitch. Appl Microbiol Biotechnol 2015; 99: 10481-10488.
Assis DA de, Matte C, Aschidamini B, et al. Biosynthesis of vitamin B12 by Propionibacterium freudenreichii subsp. shermanii ATCC 13673 using liquid acid protein residue of soybean as culture medium. Biotechnol Prog. Epub ahead of print 2020. DOI: 10.1002/btpr.3011.
Wang Z, Ammar EM, Zhang A, et al. Engineering Propionibacterium freudenreichii subsp. Shermanii for enhanced propionic acid fermentation: Effects of overexpressing propionyl-CoA: Succinate CoA transferase. Metab Eng 2015; 27: 46-56.
Pillai V V, Prakash G, Lali AM. Growth engineering of Propionibacterium freudenreichii shermanii for organic acids and other value-added products formation. Prep Biochem Biotechnol 2018; 48: 6-12.
Gaucher F, Bonnassie S, Rabah H, et al. Review: Adaptation of Beneficial Propionibacteria, Lactobacilli, and Bifidobacteria Improves Tolerance Toward Technological and Digestive Stresses. Front Microbiol; 10. Epub ahead of print 24 April 2019. DOI: 10.3389/fmicb.2019.00841.
Gaucher F, Gagnaire V, Rabah H, et al. Taking advantage of bacterial adaptation in order to optimize industrial production of dry propionibacterium freudenreichii. Microorganisms; 7. Epub ahead of print 1 October 2019. DOI: 10.3390/microorganisms7100477.
Gaucher F, Rabah H, Kponouglo K, et al. Intracellular osmoprotectant concentrations determine Propionibacterium freudenreichii survival during drying. Appl Microbiol Biotechnol 2020; 104: 3145-3156.
Gaucher F, Kponouglo K, Rabah H, et al. Propionibacterium freudenreichii CIRM-BIA 129 Osmoadaptation Coupled to Acid-Adaptation Increases Its Viability During Freeze-Drying. Front Microbiol; 10. Epub ahead of print 9 October 2019. DOI: 10.3389/fmicb.2019.02324.
Deptula P, Laine PK, Roberts RJ, et al. De novo assembly of genomes from long sequence reads reveals uncharted territories of Propionibacterium freudenreichii. BMC Genomics; 18. Epub ahead of print 2017. DOI: 10.1186/s12864-017-4165-9.
Jan G, Leverrier P, Pichereau V, et al. Changes in Protein Synthesis and Morphology during Acid Adaptation of Propionibacterium freudenreichii. Appl Environ Microbiol 2001; 67: 2029-2036.
Leverrier P, Dimova D, Pichereau V, et al. Susceptibility and adaptive response to bile salts in Propionibacterium freudenreichii: Physiological and proteomic anlysis. Appl Environ Microbiol 2003; 69: 3809-3818.
Leverrier P, Vissers JPC, Rouault A, et al. Mass spectrometry proteomic analysis of stress adaptation reveals both common and distinct response pathways in Propionibacterium freudenreichii. Arch Microbiol 2004; 181: 215-230.
Huang Y, Adams MC. In vitro assessment of the upper gastrointestinal tolerance of potential probiotic dairy propionibacteria. Int J Food Microbiol 2004; 91: 253-260.
Hervé C, Fondrevez M, Chéron A, et al. Transcarboxylase mRNA: A marker which evidences P. freudenreichii survival and metabolic activity during its transit in the human gut. Int J Food Microbiol 2007; 113: 303-314.
Lan A, Bruneau A, Philippe C, et al. Survival and metabolic activity of selected strains of Propionibacterium freudenreichii in the gastrointestinal tract of human microbiota-associated rats. Br J Nutr 2007; 97: 714-724.
Saraoui T, Parayre S, Guernec G, et al. A unique in vivo experimental approach reveals metabolic adaptation of the probiotic Propionibacterium freudenreichii to the colon environment. BMC Genomics; 14. Epub ahead of print 23 December 2013. DOI: 10.1186/1471-2164-14-911.
Rabah H, Ménard O, Gaucher F, et al. Cheese matrix protects the immunomodulatory surface protein SlpB of Propionibacterium freudenreichii during in vitro digestion. Food Res Int 2018; 106: 712-721.
Cousin FJ, Jouan-Lanhouet S, Dimanche-Boitrel MT, et al. Milk fermented by propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells. PLoS One; 7. Epub ahead of print 19 March 2012. DOI: 10.1371/journal.pone.0031892.
Aburjaile FF, Rohmer M, Parrinello H, et al. Adaptation of Propionibacterium freudenreichii to long-term survival under gradual nutritional shortage. BMC Genomics; 17. Epub ahead of print 8 December 2016. DOI: 10.1186/s12864-016-3367-x.
Aburjaile FF, Madec MN, Parayre S, et al. The long-term survival of Propionibacterium freudenreichii in a context of nutrient shortage. J Appl Microbiol 2016; 120: 432-440.
Cardoso FS, Castro RF, Borges N, et al. Biochemical and genetic characterization of the pathways for trehalose metabolism in Propionibacterium freudenreichii, and their role in stress response. Microbiology 2007; 153: 270-280.
Dalmasso M, Aubert J, Even S, et al. Accumulation of intracellular glycogen and trehalose by Propionibacterium freudenreichii under conditions mimicking cheese ripening in the cold. Appl Environ Microbiol 2012; 78: 6357-6364.
Huang S, Rabah H, Jardin J, et al. Hyperconcentrated Sweet Whey, a New Culture Medium That Enhances Propionibacterium freudenreichii Stress Tolerance. Appl Environ Microbiol 2016; 82: 4641-4651.
Tuomola EM, Ouwehand AC, Salminen SJ. Human ileostomy glycoproteins as a model for small intestinal mucus to investigate adhesion of probiotics. Lett Appl Microbiol 1999; 28: 159-163.
Ouwehand AC, Tölkkö S, Kulmala J, et al. Adhesion of inactivated probiotic strains to intestinal mucus. Lett Appl Microbiol 2000; 31: 82-86.
Campaniello D, Bevilacqua A, Sinigaglia M, et al. Screening of Propionibacterium spp. for potential probiotic properties. Anaerobe 2015; 34: 169-173.
do Carmo FLR, Rabah H, Huang S, et al. Propionibacterium freudenreichii surface protein SlpB is involved in adhesion to intestinal HT-29 cells. Front Microbiol 2017; 8: 1-11.
do Carmo FLR, Silva WM, Tavares GC, et al. Mutation of the surface layer protein SlpB has pleiotropic effects in the probiotic propionibacterium freudenreichii CIRM-BIA 129. Front Microbiol 2018; 9: 1807.
Collado MC, Meriluoto J, Salminen S. Development of new probiotics by strain combinations: Is it possible to improve the adhesion to intestinal mucus? J Dairy Sci 2007; 90: 2710-2716.
Vesterlund S, Karp M, Salminen S, et al. Staphylococcus aureus adheres to human intestinal mucus but can be displaced by certain lactic acid bacteria. Microbiology 2006; 152: 1819-1826.
Hajfarajollah H, Mokhtarani B, Noghabi KA. Newly Antibacterial and Antiadhesive Lipopeptide Biosurfactant Secreted by a Probiotic Strain, Propionibacterium Freudenreichii. Appl Biochem Biotechnol 2014; 174: 2725-2740.
Nair DVT, Kollanoor-Johny A. Effect of Propionibacterium freudenreichii on Salmonella multiplication, motility, and association with avian epithelial cells. Poult Sci 2017; 96: 1376-1386.
Nair DVTT, Kollanoor Johny A. Characterizing the Antimicrobial Function of a Dairy-Originated Probiotic, Propionibacterium freudenreichii, Against Multidrug-Resistant Salmonella entericaSerovar Heidelberg in Turkey Poults. Front Microbiol; 9. Epub ahead of print 12 July 2018. DOI: 10.3389/fmicb.2018.01475.
Foligné B, Deutsch S-M, Breton J, et al. Promising Immunomodulatory Effects of Selected Strains of Dairy Propionibacteria as Evidenced In Vitro and In Vivo. Appl Environ Microbiol 2010; 76: 8259-8264.
Collado MC, Jalonen L, Meriluoto J, et al. Protection mechanism of probiotic combination against human pathogens: in vitro adhesion to human intestinal mucus. Asia Pac J Clin Nutr 2006; 15: 570-575.
Myllyluoma E, Ahonen AM, Korpela R, et al. Effects of multispecies probiotic combination on Helicobacter pylori infection in vitro. Clin Vaccine Immunol; 15. Epub ahead of print September 2008. DOI: 10.1128/CVI.00080-08.
Jan G, Belzacq A-SS, Haouzi D, et al. Propionibacteria induce apoptosis of colorectal carcinoma cells via short-chain fatty acids acting on mitochondria. Cell Death Differ 2002; 9: 179-188.
Lan A, Lagadic-Gossmann D, Lemaire C, et al. Acidic extracellular pH shifts colorectal cancer cell death from apoptosis to necrosis upon exposure to propionate and acetate, major end-products of the human probiotic propionibacteria. Apoptosis 2007; 12: 573-591.
Lan A, Bruneau A, Bensaada M, et al. Increased induction of apoptosis by Propionibacterium freudenreichii TL133 in colonic mucosal crypts of human microbiota-associated rats treated with 1,2-dimethylhydrazine. Br J Nutr 2008; 100: 1251-1259.
Cousin FJ, Jouan-Lanhouet S, Théret N, et al. The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer. Oncotarget 2016; 7: 7161-7178.
Casanova MR, Azevedo-Silva J, Rodrigues LR, et al. Colorectal Cancer Cells Increase the Production of Short Chain Fatty Acids by Propionibacterium freudenreichii Impacting on Cancer Cells Survival. Front Nutr 2018; 5: 44.
Bouglé D, Roland N, Lebeurrier F. Effect of Propionibacteria Supplementation on Fecal Bifidobacteria and Segmental Colonic Transit Time in Healthy Human Subjects. Scand J Gastroenterol 1999; 34: 144-148.
Hojo K, Yoda N, Tsuchita H, et al. Effect of Ingested Culture of Propionibacterium freudenreichii ET-3 on Fecal Microflora and Stool Frequency in Healthy Females. Biosci Microflora 2002; 21: 115-120.
Kaneko T, Mori H, Iwata M, et al. Growth Stimulator for Bifidobacteria Produced by Propionibacterium freudenreichii and Several Intestinal Bacteria. J Dairy Sci 1994; 77: 393-404.
Mori H, Sato Y, Taketomo N, et al. Isolation and Structural Identification of Bifidogenic Growth Stimulator Produced by Propionibacterium freudenreichii. J Dairy Sci 1997; 80: 1959-1964.
Isawa K, Hojo K, Yoda N, et al. Isolation and identification of a new bifidogenic growth stimulator produced by propionibacterium freudenreichii ET-3. Biosci Biotechnol Biochem 2002; 66: 679-681.
Okada Y, Tsuzuki Y, Miyazaki J, et al. Propionibacterium freudenreichii component 1.4-dihydroxy-2-naphthoic acid (DHNA) attenuates dextran sodium sulphate induced colitis by modulation of bacterial flora and lymphocyte homing. Gut 2006; 55: 681-688.
Suzuki A, Mitsuyama K, Koga H, et al. Bifidogenic growth stimulator for the treatment of active ulcerative colitis: a pilot study. Nutrition 2006; 22: 76-81.
Furuichi K, Hojo K ichi, Katakura Y, et al. Aerobic culture of Propionibacterium freudenreichii ET-3 can increase production ratio of 1,4-dihydroxy-2-naphthoic acid to menaquinone. J Biosci Bioeng 2006; 101: 464-470.
Kouya T, Misawa K, Horiuchi M, et al. Production of extracellular bifidogenic growth stimulator by anaerobic and aerobic cultivations of several propionibacterial strains. J Biosci Bioeng 2007; 103: 464-471.
Foligné B, Breton J, Mater D, et al. Tracking the microbiome functionality: Focus on Propionibacterium species. Gut 2013; 62: 1227-1228.
Deutsch S-MM, Mariadassou M, Nicolas P, et al. Identification of proteins involved in the anti-inflammatory properties of Propionibacterium freudenreichii by means of a multi-strain study. Sci Rep; 7. Epub ahead of print 2017. DOI: 10.1038/srep46409.
Frohnmeyer E, Deptula P, Nyman TA, et al. Secretome profiling of Propionibacterium freudenreichii reveals highly variable responses even among the closely related strains. Microb Biotechnol 2018; 11: 510-526.
Ma S, Yeom J, Lim Y-HH. Dairy Propionibacterium freudenreichii ameliorates acute colitis by stimulating MUC2 expression in intestinal goblet cell in a DSS-induced colitis rat model. Sci Rep 2020; 10: 5523.
Colliou N, Ge Y, Gong M, et al. Regulation of Th17 cells by P. UF1 against systemic Listeria monocytogenes infection. Gut Microbes 2018; 9: 279-287.
Ge Y, Gong M, Colliou N, et al. Neonatal intestinal immune regulation by the commensal bacterium, P. UF1. Mucosal Immunol 2019; 12: 434-444.
Le Maréchal C, Peton V, Plé C, et al. Surface proteins of Propionibacterium freudenreichii are involved in its anti-inflammatory properties. J Proteomics 2015; 113: 447-461.
do Carmo FLR, Rabah H, Cordeiro BF, et al. Probiotic Propionibacterium freudenreichii requires SlpB protein to mitigate mucositis induced by chemotherapy. Oncotarget 2019; 10: 7198-7219.
Ge Y, Gong M, Zadeh M, et al. Regulating colonic dendritic cells by commensal glycosylated large surface layer protein A to sustain gut homeostasis against pathogenic inflammation. Mucosal Immunol 2020; 13: 34-46.
Rodovalho V de R, Luz BSR da, Rabah H, et al. Extracellular Vesicles Produced by the Probiotic Propionibacterium freudenreichii CIRM-BIA 129 Mitigate Inflammation by Modulating the NF-κB Pathway. Front Microbiol 2020; 11: 1544.
Okada Y, Tsuzuki Y, Narimatsu K, et al. 1,4-Dihydroxy-2-naphthoic acid from Propionibacterium freudenreichii reduces inflammation in interleukin-10-deficient mice with colitis by suppressing macrophage-derived proinflammatory cytokines. J Leukoc Biol 2013; 94: 473-480.
Fukumoto S, Toshimitsu T, Matsuoka S, et al. Identification of a probiotic bacteria-derived activator of the aryl hydrocarbon receptor that inhibits colitis. Immunol Cell Biol 2014; 92: 460-465.
Cheng Y, Jin UH, Davidson LA, et al. Microbial-derived 1,4-Dihydroxy-2-naphthoic acid and related compounds as aryl hydrocarbon receptor agonists/antagonists: Structure-activity relationships and receptor modeling. Toxicol Sci 2017; 155: 458-473.
Plé C, Richoux R, Jardin J, et al. Single-strain starter experimental cheese reveals anti-inflammatory effect of Propionibacterium freudenreichii CIRM BIA 129 in TNBS-colitis model. J Funct Foods 2015; 18: 575-585.
Foligné B, Parayre S, Cheddani R, et al. Immunomodulation properties of multi-species fermented milks. Food Microbiol 2016; 53: 60-69.
Moslemi M, Mazaheri Nezhad Fard R, Hosseini SM, et al. Incorporation of Propionibacteria in Fermented Milks as a Probiotic. Crit Rev Food Sci Nutr 2016; 56: 1290-1312.
Cousin FJ, Foligné B, Deutsch SM, et al. Assessment of the probiotic potential of a dairy product fermented by propionibacterium freudenreichii in piglets. J Agric Food Chem 2012; 60: 7917-7927.
Dudek-Wicher R, Junka A, Paleczny J, et al. Clinical Trials of Probiotic Strains in Selected Disease Entities. Int J Microbiol; 2020. Epub ahead of print 2020. DOI: 10.1155/2020/8854119.
Uchida M, Tsuboi H, Takahashi Arita M, et al. Safety of high doses of Propionibacterium freudenreichii ET-3 culture in healthy adult subjects. Regul Toxicol Pharmacol 2011; 60: 262-267.
Jan G, Leverrier P, Proudy I, et al. Survival and beneficial effects of propionibacteria in the human gut: in vivo and in vitro investigations. Lait 2002; 82: 131-144.
Kukkonen K, Savilahti E, Haahtela T, et al. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2007; 119: 192-198.
Kukkonen K, Savilahti E, Haahtela T, et al. Long-term safety and impact on infection rates of postnatal probiotic and prebiotic (synbiotic) treatment: Randomized, double-blind, placebo-controlled trial. Pediatrics 2008; 122: 8-12.
Kuitunen M, Kukkonen K, Juntunen-Backman K, et al. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol 2009; 123: 335-341.
Korpela K, Salonen A, Vepsäläinen O, et al. Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants. Microbiome; 6. Epub ahead of print 16 October 2018. DOI: 10.1186/s40168-018-0567-4.
Kallio S, Kukkonen AK, Savilahti E, et al. Perinatal probiotic intervention prevented allergic disease in a Caesarean-delivered subgroup at 13-year follow-up. Clin Exp Allergy 2018; 49: 506-515.
Tapiovaara L, Lehtoranta L, Poussa T, et al. Absence of adverse events in healthy individuals using probiotics - analysis of six randomised studies by one study group. Benef Microbes 2016; 7: 161-169.
Żółkiewicz J, Marzec A, Ruszczyński M, et al. Postbiotics—A Step Beyond Pre- and Probiotics. Nutrients 2020; 12: 2189.
Nataraj BH, Ali SA, Behare P V., et al. Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods. Microb Cell Fact 2020; 19: 168.
Tsilingiri K, Rescigno M. Postbiotics: what else? Benef Microbes 2013; 4: 101-107.
Rohde M. The Gram-Positive Bacterial Cell Wall. Gram-Positive Pathog 2019; 3-18.
Briaud P, Carroll RK. Extracellular Vesicle Biogenesis and Functions in Gram-Positive Bacteria. Infect Immun 2020; 88: 1-37.
Molina-Tijeras JA, Gálvez J, Rodríguez-Cabezas ME. The Immunomodulatory Properties of Extracellular Vesicles Derived from Probiotics: A Novel Approach for the Management of Gastrointestinal Diseases. Nutrients 2019; 11: 1038.
Liu Y, Alexeeva S, Defourny KA, et al. Tiny but mighty: bacterial membrane vesicles in food biotechnological applications. Curr Opin Biotechnol 2018; 49: 179-184.
Rad AH, Abbasi A, Kafil HS, et al. Potential Pharmaceutical and Food Applications of Postbiotics: A review. Curr Pharm Biotechnol; 21. Epub ahead of print 17 May 2020. DOI: 10.2174/1389201021666200516154833.