Lactobacillus bulgaricus GLB44: Difference between revisions

Lactobacillus bulgaricus GLB44
Scientific classification
Domain:	Bacteria
Phylum:	Bacillota
Class:	Bacilli
Order:	Lactobacillales
Family:	Lactobacillaceae
Genus:	Lactobacillus
Species:	L. delbrueckii
Subspecies:	L. d. bulgaricus

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Lactobacillus delbrueckii subsp. bulgaricus is a bacterial subspecies traditionally isolated from European yogurts.^[1] Lactobacillus bulgaricus GLB44 differs from other L. bulgaricus strains, because it was isolated from the leaves of Galanthus nivalis (common snowdrop) in Bulgaria.^[1]

General information

GLB44 is derived from the leaves of the snowdrop flower; it is the only known strain of this subspecies that has a vegan origin (not from yogurt) and it is a probiotic.^[1]

The snowdrop flower is found in European mountainous regions, and blooms between January and May, when temperatures can fall below freezing in the region.^[2]^[3] Thus, GLB44 is also naturally capable of surviving in below-freezing temperatures, allowing GLB44 to survive in plant-based aliments stored at refrigerator temperatures.

GLB44 differs from other probiotics such as L. plantarum 299v or L. rhamnosus GG which are originally extracted from the human mouth.^[4] Others like Bifidobacterium are extracted from the feaces of newborns,^[5] while others, such as some strains of L. brevis, come from the human vaginal canal.^[6] GLB44 does not have any interference with mammalian organs, only flowers, leaves and juices.^[7] This is important for multiple reasons such as the fact that there is some scientific evidence that probiotics growing in the human mouth naturally could accelerate tooth decay.^[8]

While many probiotics have major allergens in the growth solution, GLB44 has no major allergens as part of its growth medium.^[4]^[9] For example, the growth medium for L. plantarum 299v includes barley, which contains a small amount of gluten,^[4] and L. rhamnosus GG has a small amount of casein.^[9] The fact that GLB44 is grown in vegetable juice means GLB44 does not contain any of the seven major allergens for which the U.S. Food and Drug Administration requires additional labelling: lactose, gluten, soya, peanuts, tree nuts, fish, or crustacean shellfish.^[10]

Another major difference is the safety track record of L. bulgaricus, which is now over 109 years since it was scientifically isolated.^[7] There are certain similarities between L. bulgaricus GLB44 and some other probiotics. For example, L. bulgaricus, L. rhamnosus GG and L. plantarum 299v all have scientific records of their ability to pass successfully through the gastrointestinal tract.^[4]^[11]^[12]

History

The first L. bulgaricus was discovered more than a century ago, the result of a study into the unusual longevity of mountain villagers in Bulgaria (thus called L. bulgaricus) by Dr. Stamen Grigorov in 1905.^[1] In 1912, the New York Times wrote an overview article about the new discovery and the use of fermented yogurts with L. bulgaricus in Bulgaria titled “Metchnikoff Confirmed in His Theory of Long Life,” highlighting villager Vasilka, age 126, as the longest living person in the world.^[13] In Bulgarian communities there were 3,000 centenarians from a population of 3 million – six times higher than the number of centenarians per capita in the United States today.^[15] In the article the author described the discovery as follows: "In Bulgaria, the home of this bacillus, the majority of the natives live to age considerably in excess of what is recognized as the term of life among Western nations, an inquiry has shown that in the Eastern part of Southern Europe, among a population of about 3,000,000, there were more than 3,000 centenarians found performing duties which would not be assigned to a man of 65 years of age elsewhere. It is quite common to find among the peasants who live to such a large extent upon soured milk individuals of 110 and 120 years of age."

There is a complex interplay between the probiotic bacteria and the body's immune system in the large intestine, where bacteria stimulate the body's own immune system to inhibit the pathogenic bacteria.^[16] In a controlled study, 61 elderly volunteers, after 6 months of a daily dose of L. bulgaricus, responded to the intake of probiotic with an increase in the percentage of NK cells, an improvement in the parameters defining the immune risk profile (IRP), and an increase in the T cell subsets that are less differentiated. The probiotic group also showed decreased concentrations of the pro-inflammatory cytokine IL-8 but increased antimicrobial peptide hBD-2.^[16]

Safety of use

Due to more than a century of safe use, the FDA has granted L. bulgaricus a "grandfather" status, with an automatic GRAS status (generally recognized as safe).^[17] Moreover, the Code of Federal Regulations mandates that in the US, for a product to be called yogurt, it must contain two specific strains of lactic acid bacteria: Lactobacillus bulgaricus and Streptococcus thermophilus, as regulated by the FDA.^[18]

L. bulgaricus GLB44 is a safe product, without limitations of the quantity consumed. It is also recommendable for the elderly^[19] as it helps reduce infections such as the common cold, as well as for young children (i.e., when they suffer from acute diarrhea^[20]). Harvard Women's Health Watch, published by Harvard Medical School, recommends a GLB44 dose range of between 1 and 10 billion colony forming units (CFU) per day, the amount contained in a capsule or two several days a week.^[21]

GLB44 is not a bacterium that can live naturally in the human mouth, as presented by the Human Oral Microbiome Database.^[22] A study conducted by the University of Texas uncovered that while a bacterium called S. mutans is the biggest culprit for tooth decay, various lactobacilli are also associated with the progression of lesions.^[23] GLB44 does not increase the risk of tooth decay due to its inability to live in the human mouth,^[22] an advantage versus other probiotics that contain any of the following lactobacilli that live naturally in the human mouth and could contribute to the tooth decay: L. acidophilus,^[22] L. brevis,^[22] L. casei,^[22] L. fermentum,^[22] L. gasseri,^[22] L. paracasei,^[22] L plantarum,^[22] L. reuteri,^[22] L. rhamnosus,^[22] L. salivarius.^[22]

L. bulgaricus GLB44 and the definition of probiotics

The U.S. Food and Drug Administration (FDA) has presented on their website the following guideline: “Guidance for Industry on Complementary and Alternative Medicine Products and Their Regulation by the Food and Drug Administration”^[24] In this article, the definition of "Probiotics" is twofold: 1) live microbial food supplements that beneficially affect the host by improving its intestinal microbial; 2) live microorganisms which, when consumed in adequate amounts of food, confer a health benefit on the host.

Another guideline presented on the FDA website, "Guidelines for Evaluation of Probiotics in Food",^[25] has outlined more specific criteria for the definition of effective probiotic based on the following criteria:

Resistance to gastric acidity
Bile acid resistance
Adherence to mucus and/or human epithelial cells and cell lines
Antimicrobial activity against potentially pathogenic bacteria
Ability to reduce pathogen adhesion to surfaces
Bile salt hydrolase activity

The authors of this guideline specifically outline L. bulgaricus as an example of an effective probiotic with suitable scientific substantiation of health benefits.^[25]

Resistance to gastric acid and bile acid are scientifically presented in the following studies where L. bulgaricus successfully passes through the human intestinal tract, maintaining its viability: “Survival of Yogurt Bacteria in the Human Gut”^[11] and “Lactobacillus delbrueckii subsp. bulgaricus Collection to select a strain able to survive to the human intestinal tract.”.^[26] Adherence to mucus and human epithelial cells and cell lines and the ability to reduce pathogen adhesion to surfaces is scientifically proven by the research "Influence of Gastrointestinal System Conditions on Adhesion of exopolysaccharide-producing Lactobacillus delbrueckii subsp. bulgaricus strains to Caco-2 Cells"^[27]

There are also numerous studies that outline the antimicrobial activity of L. bulgaricus against potentially pathogenic bacteria such as E. Coli,^[21] Salmonella sp.,^[21] S. aureus,^[21] V. cholera,^[21] B. subtilis,^[21] C. difficile^[20] and others.

References

^ ^a ^b ^c ^d Michaylova, M; Minkova, S; Kimura, K; Sasaki, T; Isawa, K (April 2007). "Isolation and characterization of Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus from plants in Bulgaria". FEMS Microbiology Letters. 269 (1): 160–9. doi:10.1111/j.1574-6968.2007.00631.x. PMID 17257163.
^ ^a ^b "Galanthus alpinus [Sosn. ]". citesbulbs.myspecies.info. Retrieved 2023-03-11.
^ Peev D, Vladimirov V (2013). "Galanthus nivalis". Red Data Book of the Republic of Bulgaria. Institute of Biodiversity and Ecosystem Research – Bulgarian Academy of Science Electronic Database.
^ ^a ^b ^c ^d Goran Moulin (2010) Lactobacillus plantarum 299v as available on the manufacturer website: "Archived copy" (PDF). Archived from the original (PDF) on 2010-08-20. Retrieved 2014-06-03.{{cite web}}: CS1 maint: archived copy as title (link)
^ Bezirtzoglou, E; Romond, C (1990). "Occurrence of Bifidobacterium in the feces of newborns delivered by cesarean section". Biology of the Neonate. 58 (5): 247–51. doi:10.1159/000243275. PMID 2076442.
^ Antonio, MA; Hawes, SE; Hillier, SL (December 1999). "The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species". The Journal of Infectious Diseases. 180 (6): 1950–6. doi:10.1086/315109. PMID 10558952.
^ ^a ^b GLB44 patent pending status as reported on the branded product website: www.proviotic.com
^ Schwendicke, F; Dörfer, C; Kneist, S; Meyer-Lueckel, H; Paris, S (2014). "Cariogenic effects of probiotic Lactobacillus rhamnosus GG in a dental biofilm model". Caries Research. 48 (3): 186–92. doi:10.1159/000355907. PMID 24480927. S2CID 11641425.
^ ^a ^b Mark Hyman (2014) "The Health Living Store" as available on the website: http://store.drhyman.com/Store/Show/ListAlphabetically/378/Culturelle-with-Lactobacillus-GG
^ "Food Facts" (PDF). (June 2010). The US Food and Drug Administration Center for Food Safety. Retrieved 30 May 2014., Website Content: https://www.fda.gov/downloads/Food/ResourcesForYou/Consumers/UCM220117.pdf
^ ^a ^b Elli, M; Callegari, ML; Ferrari, S; Bessi, E; Cattivelli, D; Soldi, S; Morelli, L; Goupil Feuillerat, N; Antoine, JM (July 2006). "Survival of yogurt bacteria in the human gut". Applied and Environmental Microbiology. 72 (7): 5113–7. Bibcode:2006ApEnM..72.5113E. doi:10.1128/AEM.02950-05. PMC 1489325. PMID 16820518.
^ Conway, PL; Gorbach, SL; Goldin, BR (January 1987). "Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells". Journal of Dairy Science. 70 (1): 1–12. doi:10.3168/jds.S0022-0302(87)79974-3. PMID 3106442.
^ ^a ^b "Metchnikoff Confirmed In His Theory Of Long Life" (PDF). The New York Times. January 21, 1912. Retrieved 30 May 2014.
^ Douglas, Loudon M. (1911). The Bacillus of Long Life (1911 revised ed.). New York: The Knickerbocker Press.
^ Meyer, J (December 2012). "Centenarians: 2010, Special Census Report" (PDF). U.S. Census Bureau. U.S. Department of Commerce Economics and Statistics Administration.
^ ^a ^b Moro-García, MA; Alonso-Arias, R; Baltadjieva, M; Fernández Benítez, C; Fernández Barrial, MA; Díaz Ruisánchez, E; Alonso Santos, R; Alvarez Sánchez, M; Saavedra Miján, J; López-Larrea, C (August 2013). "Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects". Age. 35 (4): 1311–26. doi:10.1007/s11357-012-9434-6. PMC 3705123. PMID 22645023.
^ "CRN List of Dietary Ingredients "Grandfathered" under DSHEA" (PDF). Council for Responsible Nutrition (1998). National Nutritional Foods Association. Retrieved 31 May 2014.
^ "Title 21--Food And Drugs Chapter I--Food And Drug Administration Department Of Health And Human Services Subchapter B--Food For Human Consumption Part 131 Milk And Cream". FDA Website (21CFR131). US Food and Drug Administration (2013). Retrieved 31 May 2014.
^ Makino, S; Ikegami, S; Kume, A; Horiuchi, H; Sasaki, H; Orii, N (October 2010). "Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1". The British Journal of Nutrition. 104 (7): 998–1006. doi:10.1017/S000711451000173X. PMID 20487575.
^ ^a ^b Banerjee, Pratik; Merkel, Glenn J; Bhunia, Arun K (2009). "Lactobacillus delbrueckii ssp. bulgaricus B-30892 can inhibit cytotoxic effects and adhesion of pathogenic Clostridium difficile to Caco-2 cells". Gut Pathogens. 1 (1): 8. doi:10.1186/1757-4749-1-8. PMC 2680912. PMID 19397787.
^ ^a ^b ^c ^d ^e ^f Harvard Women's Health Watch (2005). "Benefit of Probiotics: Should you take a daily dose of bacteria?". from Harvard University Website. Retrieved 26 May 2014.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Chen T, Dewhirst F, Izard J, Paster J, Tanner A, Wade W (2014) "Human Oral Microbiome Database" available on the electronic website: www.homd.org
^ Loesche, Walter J. (1996). "Microbiology of Dental Decay and Periodontal Disease". In Baron, Samuel (ed.). Medical Microbiology (4th ed.). Galveston: University of Texas Medical Branch at Galveston. ISBN 9780963117212. PMID 21413316.
^ US Food and Drug Administration (2006). "Guidance for Industry on Complementary and Alternative Medicine Products and Their Regulation by the Food and Drug Administration" (PDF). U.S. Department of Health and Human Services Food and Drug Administration. FDA.
^ ^a ^b Food and Agriculture Organization of the United Nations, World Health Organization (2002) "Guidelines for the Evaluation of Probiotics" available on the FDA website: https://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-rpt0282-tab-03-ref-19-joint-faowho-vol219.pdf
^ Vázquez, C; Botella-Carretero, JI; García-Albiach, R; Pozuelo, MJ; Rodríguez-Baños, M; Baquero, F; Baltadjieva, MA; del Campo, R (Jul–Aug 2013). "Screening in a Lactobacillus delbrueckii subsp. bulgaricus collection to select a strain able to survive to the human intestinal tract". Nutricion Hospitalaria. 28 (4): 1227–35. doi:10.3305/nh.2013.28.4.6540. ISSN 0212-1611. PMID 23889646.
^ Darilmaz, D; AslımII B; SuludereII Z; Akca G (2011). "Influence of gastrointestinal system conditions on adhesion of exopolysaccharide-producing Lactobacillus delbrueckii subsp. bulgaricus strains to caco-2 cells". Braz. Arch. Biol. Technol. 54, n.5 (5): 917–26. doi:10.1590/S1516-89132011000500009. ISSN 1516-8913.

[Source1-1] Michaylova, M; Minkova, S; Kimura, K; Sasaki, T; Isawa, K (April 2007). "Isolation and characterization of Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus from plants in Bulgaria". FEMS Microbiology Letters. 269 (1): 160–9. doi:10.1111/j.1574-6968.2007.00631.x. PMID 17257163.

[Source33-2] "Galanthus alpinus [Sosn. ]". citesbulbs.myspecies.info. Retrieved 2023-03-11.

[Source2-3] Peev D, Vladimirov V (2013). "Galanthus nivalis". Red Data Book of the Republic of Bulgaria. Institute of Biodiversity and Ecosystem Research – Bulgarian Academy of Science Electronic Database.

[Source38-4] Goran Moulin (2010) Lactobacillus plantarum 299v as available on the manufacturer website: "Archived copy" (PDF). Archived from the original (PDF) on 2010-08-20. Retrieved 2014-06-03.{{cite web}}: CS1 maint: archived copy as title (link)

[Source45-5] Bezirtzoglou, E; Romond, C (1990). "Occurrence of Bifidobacterium in the feces of newborns delivered by cesarean section". Biology of the Neonate. 58 (5): 247–51. doi:10.1159/000243275. PMID 2076442.

[Source46-6] Antonio, MA; Hawes, SE; Hillier, SL (December 1999). "The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species". The Journal of Infectious Diseases. 180 (6): 1950–6. doi:10.1086/315109. PMID 10558952.

[Source37-7] GLB44 patent pending status as reported on the branded product website: www.proviotic.com

[Source42-8] Schwendicke, F; Dörfer, C; Kneist, S; Meyer-Lueckel, H; Paris, S (2014). "Cariogenic effects of probiotic Lactobacillus rhamnosus GG in a dental biofilm model". Caries Research. 48 (3): 186–92. doi:10.1159/000355907. PMID 24480927. S2CID 11641425.

[Source39-9] Mark Hyman (2014) "The Health Living Store" as available on the website: http://store.drhyman.com/Store/Show/ListAlphabetically/378/Culturelle-with-Lactobacillus-GG

[Source7-10] "Food Facts" (PDF). (June 2010). The US Food and Drug Administration Center for Food Safety. Retrieved 30 May 2014., Website Content: https://www.fda.gov/downloads/Food/ResourcesForYou/Consumers/UCM220117.pdf

[Source27-11] Elli, M; Callegari, ML; Ferrari, S; Bessi, E; Cattivelli, D; Soldi, S; Morelli, L; Goupil Feuillerat, N; Antoine, JM (July 2006). "Survival of yogurt bacteria in the human gut". Applied and Environmental Microbiology. 72 (7): 5113–7. Bibcode:2006ApEnM..72.5113E. doi:10.1128/AEM.02950-05. PMC 1489325. PMID 16820518.

[Source41-12] Conway, PL; Gorbach, SL; Goldin, BR (January 1987). "Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells". Journal of Dairy Science. 70 (1): 1–12. doi:10.3168/jds.S0022-0302(87)79974-3. PMID 3106442.

[Source8-13] "Metchnikoff Confirmed In His Theory Of Long Life" (PDF). The New York Times. January 21, 1912. Retrieved 30 May 2014.

[Source34-14] Douglas, Loudon M. (1911). The Bacillus of Long Life (1911 revised ed.). New York: The Knickerbocker Press.

[Source9-15] Meyer, J (December 2012). "Centenarians: 2010, Special Census Report" (PDF). U.S. Census Bureau. U.S. Department of Commerce Economics and Statistics Administration.

[Source44-16] Moro-García, MA; Alonso-Arias, R; Baltadjieva, M; Fernández Benítez, C; Fernández Barrial, MA; Díaz Ruisánchez, E; Alonso Santos, R; Alvarez Sánchez, M; Saavedra Miján, J; López-Larrea, C (August 2013). "Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects". Age. 35 (4): 1311–26. doi:10.1007/s11357-012-9434-6. PMC 3705123. PMID 22645023.

[Source20-17] "CRN List of Dietary Ingredients "Grandfathered" under DSHEA" (PDF). Council for Responsible Nutrition (1998). National Nutritional Foods Association. Retrieved 31 May 2014.

[Source21-18] "Title 21--Food And Drugs Chapter I--Food And Drug Administration Department Of Health And Human Services Subchapter B--Food For Human Consumption Part 131 Milk And Cream". FDA Website (21CFR131). US Food and Drug Administration (2013). Retrieved 31 May 2014.

[Source122-19] Makino, S; Ikegami, S; Kume, A; Horiuchi, H; Sasaki, H; Orii, N (October 2010). "Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1". The British Journal of Nutrition. 104 (7): 998–1006. doi:10.1017/S000711451000173X. PMID 20487575.

[Source19-20] Banerjee, Pratik; Merkel, Glenn J; Bhunia, Arun K (2009). "Lactobacillus delbrueckii ssp. bulgaricus B-30892 can inhibit cytotoxic effects and adhesion of pathogenic Clostridium difficile to Caco-2 cells". Gut Pathogens. 1 (1): 8. doi:10.1186/1757-4749-1-8. PMC 2680912. PMID 19397787.

[Source242-21] ^ ^a ^b ^c ^d ^e ^f Harvard Women's Health Watch (2005). "Benefit of Probiotics: Should you take a daily dose of bacteria?". from Harvard University Website. Retrieved 26 May 2014.

[Source31-22] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Chen T, Dewhirst F, Izard J, Paster J, Tanner A, Wade W (2014) "Human Oral Microbiome Database" available on the electronic website: www.homd.org

[Source32-23] Loesche, Walter J. (1996). "Microbiology of Dental Decay and Periodontal Disease". In Baron, Samuel (ed.). Medical Microbiology (4th ed.). Galveston: University of Texas Medical Branch at Galveston. ISBN 9780963117212. PMID 21413316.

[Source25-24] US Food and Drug Administration (2006). "Guidance for Industry on Complementary and Alternative Medicine Products and Their Regulation by the Food and Drug Administration" (PDF). U.S. Department of Health and Human Services Food and Drug Administration. FDA.

[Source26-25] Food and Agriculture Organization of the United Nations, World Health Organization (2002) "Guidelines for the Evaluation of Probiotics" available on the FDA website: https://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-rpt0282-tab-03-ref-19-joint-faowho-vol219.pdf

[Source28-26] Vázquez, C; Botella-Carretero, JI; García-Albiach, R; Pozuelo, MJ; Rodríguez-Baños, M; Baquero, F; Baltadjieva, MA; del Campo, R (Jul–Aug 2013). "Screening in a Lactobacillus delbrueckii subsp. bulgaricus collection to select a strain able to survive to the human intestinal tract". Nutricion Hospitalaria. 28 (4): 1227–35. doi:10.3305/nh.2013.28.4.6540. ISSN 0212-1611. PMID 23889646.

[Source29-27] Darilmaz, D; AslımII B; SuludereII Z; Akca G (2011). "Influence of gastrointestinal system conditions on adhesion of exopolysaccharide-producing Lactobacillus delbrueckii subsp. bulgaricus strains to caco-2 cells". Braz. Arch. Biol. Technol. 54, n.5 (5): 917–26. doi:10.1590/S1516-89132011000500009. ISSN 1516-8913.

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@@ Line 1: / Line 1: @@
 {{Short description|Subspecies of bacterium}}
 {{DISPLAYTITLE:''Lactobacillus bulgaricus'' GLB44}}
-{{multiple issues|{{advert|date=October 2022}}}}
+{{advert|date=October 2022}}
-[[Lactobacillus delbrueckii subsp. bulgaricus|''Lactobacillus delbrueckii'' subsp. ''bulgaricus'']] is a bacterial subspecies traditionally isolated from European [[yogurt]]s.<ref name="Source1">{{cite journal |last1=Michaylova |first1=M |last2=Minkova |first2=S |last3=Kimura |first3=K |last4=Sasaki |first4=T |last5=Isawa |first5=K |name-list-style=vanc |date=April 2007 |title=Isolation and characterization of ''Lactobacillus delbrueckii'' ssp. ''bulgaricus'' and ''Streptococcus thermophilus'' from plants in Bulgaria |journal=FEMS Microbiology Letters |volume=269 |issue=1 |pages=160–9 |doi=10.1111/j.1574-6968.2007.00631.x |pmid=17257163 |doi-access=free}}</ref> '''''Lactobacillus bulgaricus''''' '''GLB44''' differs from the rest of the ''L. bulgaricus'' [[Strain (biology)|strains]] as it was isolated from the leaves of ''[[Galanthus nivalis]]'' (snowdrop flower) in [[Bulgaria]].<ref name="Source1" /> {{Taxobox
+[[Lactobacillus delbrueckii subsp. bulgaricus|''Lactobacillus delbrueckii'' subsp. ''bulgaricus'']] is a bacterial subspecies traditionally isolated from European [[yogurt]]s.<ref name="Source1">{{cite journal |last1=Michaylova |first1=M |last2=Minkova |first2=S |last3=Kimura |first3=K |last4=Sasaki |first4=T |last5=Isawa |first5=K |date=April 2007 |title=Isolation and characterization of ''Lactobacillus delbrueckii'' ssp. ''bulgaricus'' and ''Streptococcus thermophilus'' from plants in Bulgaria |journal=FEMS Microbiology Letters |volume=269 |issue=1 |pages=160–9 |doi=10.1111/j.1574-6968.2007.00631.x |pmid=17257163 |doi-access=free}}</ref> '''''Lactobacillus bulgaricus''''' '''GLB44''' differs from other ''L. bulgaricus'' [[Strain (biology)|strains]], because it was isolated from the leaves of ''[[Galanthus nivalis]]'' (common snowdrop) in [[Bulgaria]].<ref name="Source1" />
+{{Taxobox
 | name = ''Lactobacillus bulgaricus'' '''GLB44'''
 | image = Microscopic_Image_Lactobacillus_bulgaricus_GLB44.jpg
@@ Line 14: / Line 17: @@
 | subspecies = '''''L. d. bulgaricus'''''
 }}
-== General information: GLB44 ==
-GLB44 is derived from the leaves of the snowdrop flower; it is the only known strain of this subspecies that has vegan origin (not from yogurt) available as a commercial [[probiotic]].<ref name="Source110" /> Probiotics are health promoting bacteria which, when consumed in adequate amounts, confer a benefit on the host,<ref name="Source242">{{cite web |last=Harvard Women's Health Watch |year=2005 |title=Benefit of Probiotics: Should you take a daily dose of bacteria? |url=http://www.health.harvard.edu/press_releases/Benefit_of_Probiotics_Should_you_take_a_daily_dose_of_bacteria |access-date=26 May 2014 |publisher=from Harvard University Website}}</ref> normally associated with positive effects on the digestive<ref name="Source132">{{cite journal |last1=Wollowski |first1=I |last2=Rechkemmer |first2=G |last3=Pool-Zobel |first3=BL |name-list-style=vanc |date=February 2001 |title=Protective role of probiotics and prebiotics in colon cancer |journal=The American Journal of Clinical Nutrition |volume=73 |issue=2 Suppl |pages=451S–455S |doi=10.1093/ajcn/73.2.451s |pmid=11157356 |doi-access=free}}</ref> and immune systems,<ref name="Source122">{{cite journal |last1=Makino |first1=S |last2=Ikegami |first2=S |last3=Kume |first3=A |last4=Horiuchi |first4=H |last5=Sasaki |first5=H |last6=Orii |first6=N |name-list-style=vanc |date=October 2010 |title=Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with ''Lactobacillus delbrueckii'' ssp. ''bulgaricus'' OLL1073R-1 |journal=The British Journal of Nutrition |volume=104 |issue=7 |pages=998–1006 |doi=10.1017/S000711451000173X |pmid=20487575 |doi-access=free}}</ref> and are usually prescribed during or after antibiotic treatment<ref name="Source47">{{cite journal |last1=Beniwal |first1=RS |last2=Arena |first2=VC |last3=Thomas |first3=L |last4=Narla |first4=S |last5=Imperiale |first5=TF |last6=Chaudhry |first6=RA |last7=Ahmad |first7=UA |name-list-style=vanc |date=October 2003 |title=A randomized trial of yogurt for prevention of antibiotic-associated diarrhea |journal=Digestive Diseases and Sciences |volume=48 |issue=10 |pages=2077–82 |doi=10.1023/A:1026155328638 |pmid=14627358 |s2cid=23021761}}</ref> to alleviate the symptoms of [[antibiotic-associated diarrhea]].<ref name="Source47" /> Probiotics are also associated with decreasing of the risk of traveler's diarrhea.<ref name="Source48">{{cite book |author=Black, F |title=Travel Medicine Proceedings of the First Conference on International Travel Medicine, Zürich, Switzerland, 5-8 April 1988 |author2=Anderson, P |author3=Orskov, J |author4=Gaarslev K |author5=Laulund, S |date=1989 |publisher=Springer Berlin Heidelberg |isbn=978-3-642-73772-5 |location=Berlin, Heidelberg |pages=333–5 |chapter=Prophylactic Efficacy of Lactobacilli on Traveler's Diarrhea |doi=10.1007/978-3-642-73772-5_70}}</ref>
+== General information ==
-The snowdrop flower, found in European mountainous regions, flowers between January and May in nature, when the temperatures can fall below freezing in this region.<ref name="Source33">{{Cite web |title=Galanthus alpinus [Sosn. ] |url=https://citesbulbs.myspecies.info/category/galanthus-wild-species/galanthus-alpinus |access-date=2023-03-11 |website=citesbulbs.myspecies.info}}</ref><ref name="Source2">{{cite web |year=2013 |title=''Galanthus nivalis'' |url=http://e-ecodb.bas.bg/rdb/en/vol1/Galnival.html |work=Red Data Book of the Republic of Bulgaria |publisher=Institute of Biodiversity and Ecosystem Research – Bulgarian Academy of Science Electronic Database |vauthors=Peev D, Vladimirov V}}</ref> Thus, GLB44 is capable of surviving in freezing temperatures. These characteristics of its natural habitat allows for GLB44 to survive and remain unaffected in foods that are plant based and stored in refrigerator temperatures.
+GLB44 is derived from the leaves of the [[Galanthus|snowdrop]] flower; it is the only known strain of this subspecies that has a vegan origin (not from yogurt) and it is a [[probiotic]].<ref name="Source1" />
+The [[Galanthus|snowdrop]] flower is found in European mountainous regions, and blooms between January and May, when temperatures can fall below freezing in the region.<ref name="Source33">{{Cite web |title=Galanthus alpinus [Sosn. ] |url=https://citesbulbs.myspecies.info/category/galanthus-wild-species/galanthus-alpinus |access-date=2023-03-11 |website=citesbulbs.myspecies.info}}</ref><ref name="Source2">{{cite web |year=2013 |title=''Galanthus nivalis'' |url=http://e-ecodb.bas.bg/rdb/en/vol1/Galnival.html |work=Red Data Book of the Republic of Bulgaria |publisher=Institute of Biodiversity and Ecosystem Research – Bulgarian Academy of Science Electronic Database |vauthors=Peev D, Vladimirov V}}</ref> Thus, GLB44 is also naturally capable of surviving in below-freezing temperatures, allowing GLB44 to survive in plant-based aliments stored at refrigerator temperatures.[[File:Sneeuwklokken (Galanthus nivalis) onder struikgewas. Locatie, Natuurterrein De Famberhorst 03.jpg|thumb|right|''[[Galanthus nivalis]]'' flowers]]
-GLB44 has inhibitory qualities against other bacteria such as ''E. Coli'' and ''Salmonella'' spp.<ref name="Source3">{{cite web|last=Onderdonk A, Professor of Pathology at Harvard Medical School|title=Scientific Test Result: www.glb44.org|url=http://glb44.org/|work=Clinical Microbiology Laboratory Brigham and Women's Hospital}}</ref> A research study was completed by [[Harvard Medical School]] professor at [[Brigham and Women's Hospital]], [http://researchfaculty.brighamandwomens.org/BRIProfile.aspx?id=655 Andrew B. Onderdonk, PhD].<ref name="Source36">Professional information for Professor Andrew Onderdonk is available on Channing Laboratory at Harvard Medical School website: {{cite web |url=http://www.channing.harvard.edu/onderdonk.htm |title=Channing Laboratory - Andrew B. Onderdonk, PhD |access-date=2014-06-03 |url-status=dead |archive-url=https://web.archive.org/web/20120623040848/http://www.channing.harvard.edu/onderdonk.htm |archive-date=2012-06-23 }}</ref> Onderdonk's study revealed GLB44's strength and effectiveness against bacterial pathogens.<ref name="Source3" /> GLB44 has patent pending status in the US for its pathogenic inhibitory qualities in vegan foods.
+[[File:Distribution of the galanthus species.png|thumb|right|The largest area in green, numbered "1" shows the ''[[Galanthus nivalis]]'' species distribution<ref name=Source33 />]]GLB44 differs from other [[Probiotic|probiotics]] such as ''[[Lactobacillus plantarum|L. plantarum]]'' 299v or ''[[Lactobacillus rhamnosus|L. rhamnosus GG]]'' which are originally extracted from the human mouth.<ref name=Source38>Goran Moulin (2010) ''Lactobacillus plantarum'' 299v as available on the manufacturer website: {{cite web |url=http://probi.se/files/2009/07/LP299v-10.pdf |title=Archived copy |access-date=2014-06-03 |url-status=dead |archive-url=https://web.archive.org/web/20100820160304/http://probi.se/files/2009/07/LP299v-10.pdf |archive-date=2010-08-20 }}</ref> Others like ''[[Bifidobacterium]]'' are extracted from the feaces of newborns,<ref name=Source45>{{cite journal |last1=Bezirtzoglou |first1=E |last2=Romond |first2=C |title=Occurrence of ''Bifidobacterium'' in the feces of newborns delivered by cesarean section |journal=Biology of the Neonate |volume=58 |issue=5 |pages=247–51 |year=1990 |pmid=2076442 |doi=10.1159/000243275}}</ref> while others, such as some strains of ''[[Lactobacillus brevis|L. brevis]]'', come from the human vaginal canal.<ref name=Source46>{{cite journal |last1=Antonio |first1=MA |last2=Hawes |first2=SE |last3=Hillier |first3=SL |title=The identification of vaginal ''Lactobacillus'' species and the demographic and microbiologic characteristics of women colonized by these species |journal=The Journal of Infectious Diseases |volume=180 |issue=6 |pages=1950–6 |date=December 1999 |pmid=10558952 |doi=10.1086/315109|doi-access=free }}</ref> [http://www.glb44.org GLB44] does not have any interference with mammalian organs, only flowers, leaves and juices.<ref name=Source37>GLB44 patent pending status as reported on the branded product website: www.proviotic.com</ref> This is important for multiple reasons such as the fact that there is some scientific evidence that probiotics growing in the human mouth naturally could accelerate [[tooth decay]].<ref name=Source42>{{cite journal |last1=Schwendicke |first1=F |last2=Dörfer |first2=C |last3=Kneist |first3=S |last4=Meyer-Lueckel |first4=H |last5=Paris |first5=S |title=Cariogenic effects of probiotic ''Lactobacillus rhamnosus'' GG in a dental biofilm model |journal=Caries Research |volume=48 |issue=3 |pages=186–92 |year=2014 |pmid=24480927 |doi=10.1159/000355907|s2cid=11641425 }}</ref>
-[[File:Sneeuwklokken (Galanthus nivalis) onder struikgewas. Locatie, Natuurterrein De Famberhorst 03.jpg|thumb|right|''Galanthus nivalis'' flowers]]
-[[File:Distribution of the galanthus species.png|thumb|right|The largest area in green, numbered "1" shows the ''Galanthus nivalis'' species distribution<ref name=Source33 />]]
-All other commercially available strains of ''L. bulgaricus'' are isolated from traditional yogurts and are grown in milk.<ref name=Source4>{{cite journal |last1=Miteva |first1=V |last2=Stefanova |first2=T |last3=Budakov |first3=I |last4=Ivanova |first4=I |last5=Mitev |first5=V |last6=Gancheva |first6=A |last7=Ljubenov |first7=M |name-list-style=vanc |title=Characterization of bacteriocins produced by strains from traditional Bulgarian dairy products |journal=Systematic and Applied Microbiology |volume=21 |issue=1 |pages=151–61 |date=March 1998 |pmid=9741120 |doi=10.1016/S0723-2020(98)80019-2}}</ref> Distinctly from the other ''L. bulgaricus'', GLB44 grows very well in vegetable juices, given its natural plant habitat.<ref name=Source3 /> Since all probiotics carry some of the organic matter in which they are grown, GLB44 carries traces of vegetable juice. GLB44 is currently grown in the [[European Union]], in vegetable juice sourced from European farms that are [[GMO]] free.<ref name=Source5>GMO Free Europe Conference (2012) Electronic Database: http://www.gmo-free-regions.org/gmo-free-regions/bulgaria.html</ref>
+While many probiotics have major [[allergen]]s in the growth solution, GLB44 has no major allergens as part of its growth medium.<ref name=Source38 /><ref name=Source39>Mark Hyman (2014) "The Health Living Store" as available on the website: http://store.drhyman.com/Store/Show/ListAlphabetically/378/Culturelle-with-Lactobacillus-GG</ref> For example, the growth medium for ''L. plantarum'' 299v includes [[barley]], which contains a small amount of [[gluten]],<ref name=Source38 /> and ''L. rhamnosus'' GG has a small amount of [[casein]].<ref name=Source39 /> The fact that GLB44 is grown in vegetable juice means GLB44 does not contain any of the seven major [[allergens]] for which the U.S. [[Food and Drug Administration]] requires additional labelling: [[lactose]], [[gluten]], [[Soya bean|soya]], peanuts, [[tree nuts]], fish, or crustacean [[shellfish]].<ref name=Source7>{{cite web|title=Food Facts|url=https://www.fda.gov/downloads/Food/ResourcesForYou/Consumers/UCM220117.pdf|work=(June 2010)|publisher=The US Food and Drug Administration Center for Food Safety|access-date=30 May 2014}}, Website Content: https://www.fda.gov/downloads/Food/ResourcesForYou/Consumers/UCM220117.pdf</ref>
-GLB44 differs from other probiotics such as ''[[Lactobacillus plantarum|L. plantarum]]'' 299v or ''[[Lactobacillus rhamnosus|L. rhamnosus GG]]'' which are originally extracted from the human mouth.<ref name=Source38>Goran Moulin (2010) ''Lactobacillus plantarum'' 299v as available on the manufacturer website: {{cite web |url=http://probi.se/files/2009/07/LP299v-10.pdf |title=Archived copy |access-date=2014-06-03 |url-status=dead |archive-url=https://web.archive.org/web/20100820160304/http://probi.se/files/2009/07/LP299v-10.pdf |archive-date=2010-08-20 }}</ref> Others like ''[[Bifidobacterium]]'' are extracted from the feces of newborns,<ref name=Source45>{{cite journal |last1=Bezirtzoglou |first1=E |last2=Romond |first2=C |name-list-style=vanc |title=Occurrence of ''Bifidobacterium'' in the feces of newborns delivered by cesarean section |journal=Biology of the Neonate |volume=58 |issue=5 |pages=247–51 |year=1990 |pmid=2076442 |doi=10.1159/000243275}}</ref> while others such as some strains of ''[[Lactobacillus brevis|L. brevis]]'' come from the human vaginal canal.<ref name=Source46>{{cite journal |last1=Antonio |first1=MA |last2=Hawes |first2=SE |last3=Hillier |first3=SL |name-list-style=vanc |title=The identification of vaginal ''Lactobacillus'' species and the demographic and microbiologic characteristics of women colonized by these species |journal=The Journal of Infectious Diseases |volume=180 |issue=6 |pages=1950–6 |date=December 1999 |pmid=10558952 |doi=10.1086/315109|doi-access=free }}</ref> [http://www.glb44.org GLB44] does not have any interference with mammalian organs, only flowers, leaves and juices.<ref name=Source37>GLB44 patent pending status as reported on the branded product website: www.proviotic.com</ref> This is important for multiple reasons such as the fact that there is some scientific evidence that if a probiotic grows in the human mouth naturally it could accelerate tooth decay.<ref name=Source42>{{cite journal |last1=Schwendicke |first1=F |last2=Dörfer |first2=C |last3=Kneist |first3=S |last4=Meyer-Lueckel |first4=H |last5=Paris |first5=S |name-list-style=vanc |title=Cariogenic effects of probiotic ''Lactobacillus rhamnosus'' GG in a dental biofilm model |journal=Caries Research |volume=48 |issue=3 |pages=186–92 |year=2014 |pmid=24480927 |doi=10.1159/000355907|s2cid=11641425 }}</ref>
+Another major difference is the safety track record of ''L. bulgaricus,'' which is now over 109 years since it was scientifically isolated.<ref name=Source37 /> There are certain similarities between ''L. bulgaricus'' GLB44 and some other probiotics. For example, ''L. bulgaricus'', ''L. rhamnosus'' GG and ''L. plantarum'' 299v all have scientific records of their ability to pass successfully through the gastrointestinal tract.<ref name=Source38 /><ref name=Source27>{{cite journal |last1=Elli |first1=M |last2=Callegari |first2=ML |last3=Ferrari |first3=S |last4=Bessi |first4=E |last5=Cattivelli |first5=D |last6=Soldi |first6=S |last7=Morelli |first7=L |last8=Goupil Feuillerat |first8=N |last9=Antoine |first9=JM |title=Survival of yogurt bacteria in the human gut |journal=Applied and Environmental Microbiology |volume=72 |issue=7 |pages=5113–7 |date=July 2006 |pmid=16820518 |pmc=1489325 |doi=10.1128/AEM.02950-05|bibcode=2006ApEnM..72.5113E }}</ref><ref name=Source41>{{cite journal |last1=Conway |first1=PL |last2=Gorbach |first2=SL |last3=Goldin |first3=BR |author-link2=Sherwood Gorbach |title=Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells |journal=Journal of Dairy Science |volume=70 |issue=1 |pages=1–12 |date=January 1987 |pmid=3106442 |doi=10.3168/jds.S0022-0302(87)79974-3|doi-access=free }}</ref>
-Also while many probiotics have major allergens in the growth solution, GLB44 has no major allergens as part of its growth medium.<ref name=Source38 /><ref name=Source39>Mark Hyman (2014) "The Health Living Store" as available on the website: http://store.drhyman.com/Store/Show/ListAlphabetically/378/Culturelle-with-Lactobacillus-GG</ref> For example, the growth medium for ''L. plantarum'' 299v includes [[barley]] that has small content of [[gluten]],<ref name=Source38 /> and ''L. rhamnosus'' GG has small content of [[casein]].<ref name=Source39 /> The fact that GLB44 is grown in vegetable juice means GLB44 does not contain any of the seven major [[allergens]] for which the U.S. [[Food and Drug Administration]] requires additional labelling: [[lactose]], [[gluten]], [[Soya bean|soya]], peanuts, [[tree nuts]], fish or crustacean [[shellfish]].<ref name=Source7>{{cite web|title=Food Facts|url=https://www.fda.gov/downloads/Food/ResourcesForYou/Consumers/UCM220117.pdf|work=(June 2010)|publisher=The US Food and Drug Administration Center for Food Safety|access-date=30 May 2014}}, Website Content: https://www.fda.gov/downloads/Food/ResourcesForYou/Consumers/UCM220117.pdf</ref>
+== History ==
-It is estimated that 30 to 50 million Americans have some degree of [[lactose intolerance]]. Certain populations are more affected than others, including 75% of African American, Jewish, Mexican and Native American, and 90% of Asian population.<ref name=Source6>WebMD medical reference website content: http://www.webmd.com/digestive-disorders/digestive-diseases-lactose-intolerance</ref> Thus, having probiotic bacteria such as GLB44 without any lactose is especially important for the lactose sensitive population.
+[[File:NYT article Photo Baba Vailka 1912.jpg|thumb|right|Living in a mountain village of Bulgaria with her son who was 101 years old, Vasilka's age was not unusual for her community, which, of note, consumed yogurt containing ''L. bulgaricus'' as a dietary staple.<ref name=Source8 /><ref name=Source34>{{cite book|last1=Douglas|first1=Loudon M.|title=The Bacillus of Long Life|date=1911|publisher=The Knickerbocker Press|location=New York|edition=1911 revised|url=http://www.gutenberg.org/files/31691/31691-h/31691-h.htm}}</ref>]]
+The first ''L. bulgaricus'' was discovered more than a century ago, the result of a study into the unusual longevity of mountain villagers in [[Bulgaria]] (thus called ''L. bulgaricus'') by [[Stamen Grigorov|Dr. Stamen Grigorov]] in 1905.<ref name=Source1 /> In 1912, the [[New York Times]] wrote an overview article about the new discovery and the use of [[fermented]] yogurts with ''L. bulgaricus'' in Bulgaria titled “[[Élie Metchnikoff|Metchnikoff]] Confirmed in His Theory of Long Life,” highlighting villager Vasilka, age 126, as the longest living person in the world.<ref name=Source8>{{cite news|title=Metchnikoff Confirmed In His Theory Of Long Life|url=https://timesmachine.nytimes.com/timesmachine/1912/01/21/100347411.pdf|access-date=30 May 2014|newspaper=The New York Times|date=January 21, 1912}}</ref> In Bulgarian communities there were 3,000 [[centenarians]] from a population of 3 million – six times higher than the number of centenarians per capita in the [[United States]] today.<ref name=Source9>{{cite web|last=Meyer|first=J|title=Centenarians: 2010, Special Census Report|url=https://www.census.gov/prod/cen2010/reports/c2010sr-03.pdf|work=U.S. Census Bureau|publisher=U.S. Department of Commerce Economics and Statistics Administration|date=December 2012}}</ref> [https://timesmachine.nytimes.com/timesmachine/1912/01/21/100347411.pdf In the article] the author described the discovery as follows: "In Bulgaria, the home of this bacillus, the majority of the natives live to age considerably in excess of what is recognized as the term of life among Western nations, an inquiry has shown that in the Eastern part of Southern Europe, among a population of about 3,000,000, there were more than 3,000 centenarians found performing duties which would not be assigned to a man of 65 years of age elsewhere. It is quite common to find among the peasants who live to such a large extent upon soured milk individuals of 110 and 120 years of age."
+There is a complex interplay between the probiotic bacteria and the body's immune system in the large intestine, where bacteria stimulate the body's own [[immune system]] to inhibit the pathogenic bacteria.<ref name=Source44>{{cite journal |last1=Moro-García |first1=MA |last2=Alonso-Arias |first2=R |last3=Baltadjieva |first3=M |last4=Fernández Benítez |first4=C |last5=Fernández Barrial |first5=MA |last6=Díaz Ruisánchez |first6=E |last7=Alonso Santos |first7=R |last8=Alvarez Sánchez |first8=M |last9=Saavedra Miján |first9=J |last10=López-Larrea |first10=C |title=Oral supplementation with ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' 8481 enhances systemic immunity in elderly subjects |journal=Age |volume=35 |issue=4 |pages=1311–26 |date=August 2013 |pmid=22645023 |pmc=3705123 |doi=10.1007/s11357-012-9434-6}}</ref> In a controlled study, 61 elderly volunteers, after 6 months of a daily dose of ''L. bulgaricus'', responded to the intake of probiotic with an increase in the percentage of [[NK cells]], an improvement in the parameters defining the immune risk profile (IRP), and an increase in the [[T cell]] subsets that are less differentiated. The probiotic group also showed decreased concentrations of the [[Proinflammatory cytokine|pro-inflammatory cytokine]] IL-8 but increased [[antimicrobial peptide]] hBD-2.<ref name=Source44 />
-Another major difference is the safety track record of ''L. bulgaricus'' is now over 109 years since it was scientifically isolated.<ref name=Source37 /> Even well-established probiotics such as ''L. rhamnosus'' and ''L. plantarum'' 299v have only a fraction of the safety record with 31 years and 21 years, respectively.<ref name=Source38 /><ref name=Source40>Patent Search (2014) on the website: http://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=4839281&KC=&FT=E&locale=en_EP</ref> On the other hand, there are certain similarities between ''L. bulgaricus'' GLB44 and some of the other probiotics. For example, ''L. bulgaricus'', ''L. rhamnosus'' GG and ''L. plantarum'' 299v all have scientific records of their ability to pass successfully through the gastrointestinal tract.<ref name=Source38 /><ref name=Source27>{{cite journal |last1=Elli |first1=M |last2=Callegari |first2=ML |last3=Ferrari |first3=S |last4=Bessi |first4=E |last5=Cattivelli |first5=D |last6=Soldi |first6=S |last7=Morelli |first7=L |last8=Goupil Feuillerat |first8=N |last9=Antoine |first9=JM |name-list-style=vanc |title=Survival of yogurt bacteria in the human gut |journal=Applied and Environmental Microbiology |volume=72 |issue=7 |pages=5113–7 |date=July 2006 |pmid=16820518 |pmc=1489325 |doi=10.1128/AEM.02950-05|bibcode=2006ApEnM..72.5113E }}</ref><ref name=Source41>{{cite journal |last1=Conway |first1=PL |last2=Gorbach |first2=SL |last3=Goldin |first3=BR |author-link2=Sherwood Gorbach |name-list-style=vanc |title=Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells |journal=Journal of Dairy Science |volume=70 |issue=1 |pages=1–12 |date=January 1987 |pmid=3106442 |doi=10.3168/jds.S0022-0302(87)79974-3|doi-access=free }}</ref> Also, they all have records of being able to inhibit to a degree [[pathogenic bacteria]].<ref name=Source3 /><ref name=Source38 /><ref name=Source41 />
-Finally, all three example probiotics in this comparison have all research tests performed by reputed academic professionals, for the case of GLB44, the research was performed by a [[Harvard Medical School]]<ref name=Source3 /> professor, for the case of ''L. rhamnosus'' GG by two [[Tufts University]] professors,<ref name=Source41 /> and for ''L. plantarum'' 299v by a professor at [[Lund University]].<ref name=Source38 /> All three probiotics have commercial brand names in the United States.
-== History of discovery: the bacillus of long life ==
-[[File:NYT article Photo Baba Vailka 1912.jpg|thumb|right|Living in a mountain village of Bulgaria with her son who was 101 years old, baba Vasilka's age was not unusual for her community, which, of note, consumed yogurt containing ''L. bulgaricus'' as a dietary staple.<ref name=Source8 /><ref name=Source34>{{cite book|last1=Douglas|first1=Loudon M.|title=The Bacillus of Long Life|date=1911|publisher=The Knickerbocker Press|location=New York|edition=1911 revised|url=http://www.gutenberg.org/files/31691/31691-h/31691-h.htm}}</ref>]]
-The first ''L. bulgaricus'' was discovered more than a century ago, the result of a study into the unusual longevity of mountain villagers in [[Bulgaria]] (thus called ''L. bulgaricus'') by [[Stamen Grigorov|Dr. Stamen Grigorov]] in 1905.<ref name=Source1 /> In 1912, the [[New York Times]] wrote an overview article about the new discovery and the use of [[fermented]] yogurts with ''L. bulgaricus'' in Bulgaria titled “[[Élie Metchnikoff|Metchnikoff]] Confirmed in His Theory of Long Life,” highlighting villager baba Vasilka, age 126, as the longest living person in the world.<ref name=Source8>{{cite news|title=Metchnikoff Confirmed In His Theory Of Long Life|url=https://timesmachine.nytimes.com/timesmachine/1912/01/21/100347411.pdf|access-date=30 May 2014|newspaper=The New York Times|date=January 21, 1912}}</ref> In fact, in these Bulgarian communities there were 3,000 [[centenarians]] from a population of 3 million – six times higher than the number of centenarians per capita in the [[United States]] today.<ref name=Source9>{{cite web|last=Meyer|first=J|title=Centenarians: 2010, Special Census Report|url=https://www.census.gov/prod/cen2010/reports/c2010sr-03.pdf|work=U.S. Census Bureau|publisher=U.S. Department of Commerce Economics and Statistics Administration|date=December 2012}}</ref> [https://timesmachine.nytimes.com/timesmachine/1912/01/21/100347411.pdf In the article] the author described the discovery as follows: "In Bulgaria, the home of this bacillus, the majority of the natives live to age considerably in excess of what is recognized as the term of life among Western nations, an inquiry has shown that in the Eastern part of Southern Europe, among a population of about 3,000,000, there were more than 3,000 centenarians found performing duties which would not be assigned to a man of 65 years of age elsewhere. It is quite common to find among the peasants who live to such a large extent upon soured milk individuals of 110 and 120 years of age."
-There is a complex interplay between the probiotic bacteria and the body's immune system in the large intestine, where the good bacteria stimulate the body's own [[immune system]] to inhibit the pathogenic bacteria.<ref name=Source44>{{cite journal |last1=Moro-García |first1=MA |last2=Alonso-Arias |first2=R |last3=Baltadjieva |first3=M |last4=Fernández Benítez |first4=C |last5=Fernández Barrial |first5=MA |last6=Díaz Ruisánchez |first6=E |last7=Alonso Santos |first7=R |last8=Alvarez Sánchez |first8=M |last9=Saavedra Miján |first9=J |last10=López-Larrea |first10=C |name-list-style=vanc |title=Oral supplementation with ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' 8481 enhances systemic immunity in elderly subjects |journal=Age |volume=35 |issue=4 |pages=1311–26 |date=August 2013 |pmid=22645023 |pmc=3705123 |doi=10.1007/s11357-012-9434-6}}</ref> For example, in a controlled study, 61 elderly volunteers, after 6 months of a daily dose of ''L. bulgaricus'', responded to the intake of probiotic with an increase in the percentage of [[NK cells]], an improvement in the parameters defining the immune risk profile (IRP), and an increase in the [[T cell]] subsets that are less differentiated. The probiotic group also showed decreased concentrations of the [[Proinflammatory cytokine|pro-inflammatory cytokine]] IL-8 but increased [[antimicrobial peptide]] hBD-2.<ref name=Source44 />
-== GLB44 studies at Brigham and Women’s Hospital ==
-Dr. Andrew Onderdonk, a [[Pathology]] Professor at [[Harvard Medical School]] and a [http://www.brighamandwomens.org/Departments_and_Services/pathology/services/clinicallabs/default.aspx Director of the Clinical Microbiology Laboratory at Brigham and Women’s hospital] has published one of his research tests on the following website: [http://www.glb44.org www.glb44.org], where GLB44 is tested against bacterial pathogens such as ''Salmonella'' sp. and ''E. Coli''. In his study, both ''Salmonella'' sp. and ''E. Coli'' are inhibited when mixed with GLB44 in [[vegetable juice]].<ref name=Source3 /> The study confirms that GLB44 is a specific [[Strain (biology)|strain]] of the ''L. bulgaricus'' subspecies, and that its inhibitory power surpasses other ''L. bulgaricus'' strains.<ref name=Source3 />
-== Scientific studies on effects ==
-These studies do not involve significant human trials sufficient for the U.S. [[Food and Drug Administration]] to allow representative [[Health claims on food labels|health claims]],<ref name=Source35>{{cite web|last=FDA (2013)|title=Label Claims for Conventional Foods and Dietary Supplements|url=https://www.fda.gov/food/ingredientspackaginglabeling/labelingnutrition/ucm111447.htm|work=FDA website|access-date=31 May 2014}}</ref> nevertheless, these studies, performed in reputable academic institutions, provide an insight on some of the properties of this bacteria:
-#The scientific study "''In Vitro'' Cholesterol Uptake by ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' Isolates" performed at the [[University of Warsaw]] proved that ''L. bulgaricus'' has the ability to uptake cholesterol from its environment.<ref name=Source10>{{cite journal|last=Ziarno|first=M.|title=In Vitro Cholesterol Uptake by ''Lactobacillus Delbrueckii'' Subsp. ''Bulgaricus'' Isolates |journal=Acta Sci. Pol., Technol. Aliment|date=2009|volume=8|issue=2|pages=21–32|url=http://www.food.actapol.net/pub/2_2_2009.pdf|access-date=31 May 2014|issn=1644-0730}}</ref>
-#''[[Helicobacter pylori]]'' bacterial infection is associated with [[chronic gastritis]], [[peptic ulcer disease]], and [[gastric cancer]]. The scientific study "Anti-''Helicobacter pylori'' activity of ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' strains" performed by the [[Medical University of Sofia]] concluded that all tested ''L. bulgaricus'' strains inhibited a number of ''H. pylori'' strains.<ref name=Source11>{{cite journal |last1=Boyanova |first=L. |last2=Stephanova-Kondratenko |first2=M. |last3=Mitov |first3=I. |title=Anti-''Helicobacter pylori'' activity of ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' strains: preliminary report |journal=Letters in Applied Microbiology |date=May 2009 |volume=48 |issue=5 |pages=579–84 |doi=10.1111/j.1472-765X.2009.02571.x|pmid=19291217 |s2cid=12637299 }}</ref>
-#In 2010, the ''[[British Journal of Nutrition]]'' reported a study that included fifty-seven elderly individuals (mean age 74) and eighty-five healthy individuals (mean age 67), who consumed ''L. bulgaricus'' every day over 12-week period. The result of the study clearly showed that people who consumed ''L. bulgaricus'' daily had 2.6 times lower incidence of catching a cold.<ref name="Source122" /> The study concluded that the consumption of yogurt fermented with ''L. bulgaricus'' augmented natural killer cell activity and reduced the risk of catching the common cold in elderly individuals.
-#The Federal Research Centre for Nutrition in Germany reported that consuming ''L. bulgaricus'' on regular basis is associated with anticarcinogenic effects, one mechanism of which is the detoxification of [[genotoxins]] in the gut.<ref name="Source132" /> This mechanism was shown experimentally in animals with use of the rat colon [[carcinogen]], with endpoints that ranging from [[tumorigenesis]] to induction of [[DNA]] damage.<ref name="Source132" />
-#The ''[[Journal of Dairy Science]]'' reports that ''L. bulgaricus'' can act as a suppressant of [[allergic inflammation]].<ref name=Source14>{{cite journal |first1=Hiroshi |last1=Kano |first2=Junko |last2=Kita |first3=Seiya |last3=Makino |first4=Shuji |last4=Ikegami |first5=Hiroyuki |last5=Itoh |date=June 2013 |title=Oral administration of ''Lactobacillus delbrueckii'' subspecies ''bulgaricus'' OLL1073R-1 suppresses inflammation by decreasing interleukin-6 responses in a murine model of atopic dermatitis |journal=Journal of Dairy Science |volume=96 |issue=6 |pages=3525–34 |pmid=23548305 |doi=10.3168/jds.2012-6514|doi-access=free }}</ref> Allergic inflammation is an important pathophysiological feature of several disabilities or medical conditions including [[allergic asthma]], [[atopic dermatitis]], [[allergic rhinitis]] and several ocular allergic diseases.<ref name=Source15>{{cite journal |last1=Fireman |first1=Philip |year=2003 |title=Understanding asthma pathophysiology |journal=Allergy and Asthma Proceedings |volume=24 |issue=2 |pages=79–83 |pmid=12776439 |url=http://openurl.ingenta.com/content/nlm?genre=article&issn=1088-5412&volume=24&issue=2&spage=79&aulast=Fireman}}</ref><ref name=Source16>{{cite journal |last1=Leung |first1=Donald Y. M. |date=March 1998 |title=Molecular basis of allergic diseases |journal=Molecular Genetics and Metabolism |volume=63 |issue=3 |pages=157–67 |pmid=9608537 |doi=10.1006/mgme.1998.2682}}</ref><ref name=Source17>{{cite journal |last1=Hansen |first1=Inga |last2=Klimek |first2=Ludger |last3=Mösges |first3=Ralph |last4=Hörmann |first4=Karl |date=June 2004 |title=Mediators of inflammation in the early and the late phase of allergic rhinitis |journal=Current Opinion in Allergy and Clinical Immunology |volume=4 |issue=3 |pages=159–63 |pmid=15126935 |doi=10.1097/00130832-200406000-00004|s2cid=46719364 }}</ref><ref name=Source18>{{cite journal |last1=Katelaris |first1=CH |name-list-style=vanc |title=Ocular allergy: implications for the clinical immunologist |journal=Annals of Allergy, Asthma & Immunology |volume=90 |issue=6 Suppl 3 |pages=23–7 |date=June 2003 |pmid=12839109 |doi=10.1016/S1081-1206(10)61656-0}}</ref>
-#''[[Clostridium difficile (bacteria)|Clostridium difficile]]'' is the most common cause of [[Antibiotic-associated diarrhea]], and the resulting [[Clostridium difficile colitis|C. difficile mediated infection]] (CDI) is potentially deadly.<ref name=Source19>{{cite journal |first1=Pratik |last1=Banerjee |first2=Glenn J |last2=Merkel |first3=Arun K |last3=Bhunia |year=2009 |title=''Lactobacillus delbrueckii'' ssp. ''bulgaricus'' B-30892 can inhibit cytotoxic effects and adhesion of pathogenic ''Clostridium difficile'' to Caco-2 cells |journal=Gut Pathogens |volume=1 |issue=1 |pages=8 |pmid=19397787 |pmc=2680912 |doi=10.1186/1757-4749-1-8}}</ref> ''C. difficile'' associated diarrhea ([[CDAD]]) is manifested by severe inflammation and [[colitis]], mostly due to the release of two [[exotoxins]] by ''C. difficile'' that cause destruction of [[epithelial cells]] in the intestine.<ref name=Source19 /> The study “''Lactobacillus delbrueckii'' ssp. ''bulgaricus'' B-30892 can inhibit [[cytotoxic]] effects and adhesion of pathogenic Clostridium difficile to [[Caco-2|Caco-2 cells]] “demonstrates that ''L. bulgaricus'' can reduce the colonization of ''C. difficile'' cells in colorectal cells, and thus prevent Antibiotic Associated Diarrhea.
 == Safety of use ==
-Due to more than a century of safe use, the FDA has granted ''L. bulgaricus'' a "grandfather" status, with an automatic [[GRAS]] status ([[Generally Recognized as Safe]]).<ref name=Source20>{{cite web|title=CRN List of Dietary Ingredients "Grandfathered" under DSHEA|url=https://www.fda.gov/ohrms/dockets/dockets/05p0305/05p-0305-cr00001-04-Council-For-Responsible-Nutrition-vol1.pdf|work=Council for Responsible Nutrition (1998)|publisher=National Nutritional Foods Association|access-date=31 May 2014}}</ref> Moreover, the [[Code of Federal Regulations]] mandates that in the US, for a product to be called [[yogurt]], it must contain two specific strains of [[lactic acid bacteria]]: ''Lactobacillus bulgaricus'' and ''Streptococcus thermophilus'', as regulated by the FDA.<ref name=Source21>{{cite web|title=Title 21--Food And Drugs Chapter I--Food And Drug Administration Department Of Health And Human Services Subchapter B--Food For Human Consumption Part 131 Milk And Cream|url=http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=131&showFR=1&subpartNode=21:2.0.1.1.21.2|work=FDA Website (21CFR131)|publisher=US Food and Drug Administration (2013)|access-date=31 May 2014}}</ref>
+Due to more than a century of safe use, the [[Food and Drug Administration|FDA]] has granted ''L. bulgaricus'' a "[[Grandfather clause|grandfather]]" status, with an automatic [[GRAS]] status ([[generally recognized as safe]]).<ref name=Source20>{{cite web|title=CRN List of Dietary Ingredients "Grandfathered" under DSHEA|url=https://www.fda.gov/ohrms/dockets/dockets/05p0305/05p-0305-cr00001-04-Council-For-Responsible-Nutrition-vol1.pdf|work=Council for Responsible Nutrition (1998)|publisher=National Nutritional Foods Association|access-date=31 May 2014}}</ref> Moreover, the [[Code of Federal Regulations]] mandates that in the US, for a product to be called [[yogurt]], it must contain two specific strains of [[lactic acid bacteria]]: ''Lactobacillus bulgaricus'' and ''Streptococcus thermophilus'', as regulated by the FDA.<ref name=Source21>{{cite web|title=Title 21--Food And Drugs Chapter I--Food And Drug Administration Department Of Health And Human Services Subchapter B--Food For Human Consumption Part 131 Milk And Cream|url=http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=131&showFR=1&subpartNode=21:2.0.1.1.21.2|work=FDA Website (21CFR131)|publisher=US Food and Drug Administration (2013)|access-date=31 May 2014}}</ref>
+''L. bulgaricus'' GLB44 is a safe product, without limitations of the quantity consumed. It is also recommendable for the elderly<ref name="Source122">{{cite journal |last1=Makino |first1=S |last2=Ikegami |first2=S |last3=Kume |first3=A |last4=Horiuchi |first4=H |last5=Sasaki |first5=H |last6=Orii |first6=N |date=October 2010 |title=Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with ''Lactobacillus delbrueckii'' ssp. ''bulgaricus'' OLL1073R-1 |journal=The British Journal of Nutrition |volume=104 |issue=7 |pages=998–1006 |doi=10.1017/S000711451000173X |pmid=20487575 |doi-access=free}}</ref> as it helps reduce infections such as the common cold, as well as for young children (i.e., when they suffer from acute diarrhea<ref name="Source19">{{cite journal |last1=Banerjee |first1=Pratik |last2=Merkel |first2=Glenn J |last3=Bhunia |first3=Arun K |year=2009 |title=''Lactobacillus delbrueckii'' ssp. ''bulgaricus'' B-30892 can inhibit cytotoxic effects and adhesion of pathogenic ''Clostridium difficile'' to Caco-2 cells |journal=Gut Pathogens |volume=1 |issue=1 |pages=8 |doi=10.1186/1757-4749-1-8 |pmc=2680912 |pmid=19397787 |doi-access=free}}</ref>). ''Harvard Women's Health Watch'', published by Harvard Medical School, recommends a GLB44 dose range of between 1 and 10 billion colony forming units (CFU) per day, the amount contained in a capsule or two several days a week.<ref name="Source242">{{cite web |last=Harvard Women's Health Watch |year=2005 |title=Benefit of Probiotics: Should you take a daily dose of bacteria? |url=http://www.health.harvard.edu/press_releases/Benefit_of_Probiotics_Should_you_take_a_daily_dose_of_bacteria |access-date=26 May 2014 |publisher=from Harvard University Website}}</ref>
-Even as a direct supplement, ''L. bulgaricus'' has a track record of safe use for more than 60 years in the United States. For example, the supplement [[Lactinex]] with a different strain of ''L. bulgaricus'' has been marketed as a commercial product in the US market since 1952.<ref name=Source22>United States Patent and Trademark Office (2014) Lactinex Search at USPTO website: http://tmsearch.uspto.gov/{{vs|date=November 2014}}</ref>
+GLB44 is not a bacterium that can live naturally in the human mouth, as presented by the Human Oral Microbiome Database.<ref name=Source31>Chen T, Dewhirst F, Izard J, Paster J, Tanner A, Wade W (2014) "Human Oral Microbiome Database" available on the electronic website: www.homd.org</ref> A study conducted by the [[University of Texas]] uncovered that while a bacterium called ''S. mutans'' is the biggest culprit for tooth decay, various lactobacilli are also associated with the progression of [[lesions]].<ref name=Source32>{{cite book |last=Loesche |first=Walter J. |title=Medical Microbiology |date=1996 |publisher=University of Texas Medical Branch at Galveston |location=Galveston |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK8259/ |edition=4th |editor1-last=Baron |editor1-first=Samuel |chapter=Microbiology of Dental Decay and Periodontal Disease|pmid=21413316 |isbn=9780963117212 }}</ref> GLB44 does not increase the risk of tooth decay due to its inability to live in the human mouth,<ref name=Source31 /> an advantage versus other probiotics that contain any of the following lactobacilli that live naturally in the human mouth and could contribute to the tooth decay: ''L. acidophilus'',<ref name=Source31 /> ''L. brevis'',<ref name=Source31 /> ''L. casei'',<ref name=Source31 /> ''L. fermentum'',<ref name=Source31 /> ''L. gasseri'',<ref name=Source31 /> ''L. paracasei'',<ref name=Source31 /> ''L plantarum'',<ref name=Source31 /> ''L. reuteri'',<ref name=Source31 /> ''L. rhamnosus'',<ref name=Source31 /> ''L. salivarius.''<ref name=Source31 />
-For the last 100 years there has been not a case of overdose on probiotics,<ref name=Source23>{{cite journal |first1=Gregor |last1=Reid |first2=Jana |last2=Jass |first3=M. Tom |last3=Sebulsky |first4=John K. |last4=McCormick |date=October 2003 |title=Potential Uses of Probiotics in Clinical Practice |journal=Clinical Microbiology Reviews |volume=16 |issue=4 |pages=658–72 |pmid=14557292 |pmc=207122 |doi=10.1128/CMR.16.4.658-672.2003}}</ref> which substantiates ''L. bulgaricus'' GLB44 as an extremely safe product, without limitations of the quantity consumed. It is also recommendable for the elderly<ref name="Source122" /> as it helps reduce infections such as the common cold, as well as for young children (i.e., when they suffer from acute diarrhea<ref name=Source19 />). [http://www.health.harvard.edu/newsletters/Harvard_Womens_Health_Watch ''Harvard Women's Health Watch''], published by Harvard Medical School, recommends a GLB44 dose range of between 1 and 10 billion colony forming units (CFU) per day, the amount contained in a capsule or two several days a week.<ref name="Source24">{{cite web |last=Harvard Women's Health Watch |year=2005 |title=Benefit of Probiotics: Should you take a daily dose of bacteria? |url=http://www.health.harvard.edu/press_releases/Benefit_of_Probiotics_Should_you_take_a_daily_dose_of_bacteria |access-date=26 May 2014 |publisher=from Harvard University Website}}</ref>
-GLB44 is not a bacterium that can live naturally in the human mouth, as presented by the [http://www.homd.org/ Human Oral Microbiome Database].<ref name=Source31>Chen T, Dewhirst F, Izard J, Paster J, Tanner A, Wade W (2014) "Human Oral Microbiome Database" available on the electronic website: www.homd.org</ref> A study conducted by the [[University of Texas]] uncovered that while a bacterium called ''S. mutans'' is the biggest culprit for tooth decay, various lactobacilli are also associated with the progression of [[lesions]].<ref name=Source32>{{cite book |last=Loesche |first=Walter J. |title=Medical Microbiology |date=1996 |publisher=University of Texas Medical Branch at Galveston |location=Galveston |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK8259/ |edition=4th |editor1-last=Baron |editor1-first=Samuel |chapter=Microbiology of Dental Decay and Periodontal Disease|pmid=21413316 |isbn=9780963117212 }}</ref> GLB44 does not increase the risk of tooth decay due to its inability to live in the human mouth,<ref name=Source31 /> an advantage versus other probiotics that contain any of the following lactobacilli that live naturally in the human mouth and could contribute to the tooth decay: ''L. acidophilus'',<ref name=Source31 /> ''L. brevis'',<ref name=Source31 /> ''L. casei'',<ref name=Source31 /> ''L. fermentum'',<ref name=Source31 /> ''L. gasseri'',<ref name=Source31 /> ''L. paracasei'',<ref name=Source31 /> ''L plantarum'',<ref name=Source31 /> ''L. reuteri'',<ref name=Source31 /> ''L. rhamnosus'',<ref name=Source31 /> ''L. salivarius''<ref name=Source31 />
 == ''L. bulgaricus'' GLB44 and the definition of probiotics ==
-The U.S. [[Food and Drug Administration]] (FDA) has presented on their website the following guideline: “Guidance for Industry on Complementary and Alternative Medicine Products and Their Regulation by the Food and Drug Administration”<ref name=Source25>{{cite web|title=Guidance for Industry on Complementary and Alternative Medicine Products and Their Regulation by the Food and Drug Administration|url=https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm145405.pdf|work=U.S. Department of Health and Human Services Food and Drug Administration|publisher=FDA |author=US Food and Drug Administration|year=2006}}</ref> In this article, the definition of "Probiotics" is twofold: 1) live [[microbial]] [[food supplements]] that beneficially affect the host by improving its intestinal microbial; 2) live microorganisms which, when consumed in adequate amounts of food, confer a health benefit on the host.
+The U.S. [[Food and Drug Administration]] ([[Food and Drug Administration|FDA]]) has presented on their website the following guideline: “Guidance for Industry on Complementary and Alternative Medicine Products and Their Regulation by the Food and Drug Administration”<ref name=Source25>{{cite web|title=Guidance for Industry on Complementary and Alternative Medicine Products and Their Regulation by the Food and Drug Administration|url=https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm145405.pdf|work=U.S. Department of Health and Human Services Food and Drug Administration|publisher=FDA |author=US Food and Drug Administration|year=2006}}</ref> In this article, the definition of "Probiotics" is twofold: 1) live [[microbial]] [[food supplements]] that beneficially affect the host by improving its intestinal microbial; 2) live microorganisms which, when consumed in adequate amounts of food, confer a health benefit on the host.
-Another guideline presented on the FDA website "Guidelines for Evaluation of Probiotics in Food"<ref name=Source26>Food and Agriculture Organization of the United Nations, World Health Organization (2002) "Guidelines for the Evaluation of Probiotics" available on the FDA website: https://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-rpt0282-tab-03-ref-19-joint-faowho-vol219.pdf</ref> has outlined more specific criteria for the definition of effective probiotic based on the following criteria:
+Another guideline presented on the [[Food and Drug Administration|FDA]] website, "Guidelines for Evaluation of Probiotics in Food",<ref name=Source26>Food and Agriculture Organization of the United Nations, World Health Organization (2002) "Guidelines for the Evaluation of Probiotics" available on the FDA website: https://www.fda.gov/ohrms/dockets/dockets/95s0316/95s-0316-rpt0282-tab-03-ref-19-joint-faowho-vol219.pdf</ref> has outlined more specific criteria for the definition of effective probiotic based on the following criteria:
 * Resistance to gastric acidity
 * [[Bile acid]] resistance
@@ Line 72: / Line 51: @@
 * Ability to reduce [[pathogen]] adhesion to surfaces
 * [[Bile salt]] hydrolase activity
-Of note, the authors of this guideline specifically outline ''L. bulgaricus'' as an example of an effective probiotic with suitable scientific substantiation of health benefits.<ref name=Source26 />
+The authors of this guideline specifically outline ''L. bulgaricus'' as an example of an effective probiotic with suitable scientific substantiation of health benefits.<ref name=Source26 />
-Resistance to gastric acid and bile acid are scientifically presented in the following studies where ''L. bulgaricus'' successfully passes through the human intestinal tract, maintaining its viability: “Survival of Yogurt Bacteria in the Human Gut”<ref name=Source27 /> and “''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' Collection to select a strain able to survive to the human intestinal tract.”.<ref name=Source28>{{cite journal|last=Vázquez|first=C|author2=Botella-Carretero, JI |author3=García-Albiach, R |author4=Pozuelo, MJ |author5=Rodríguez-Baños, M |author6=Baquero, F |author7=Baltadjieva, MA |author8= del Campo, R |title=Screening in a ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' collection to select a strain able to survive to the human intestinal tract.|journal=Nutricion Hospitalaria|date=Jul–Aug 2013|volume=28|issue=4|pages=1227–35|doi=10.3305/nh.2013.28.4.6540|pmid=23889646|issn=0212-1611|postscript=• CODEN NUHOEQ S.V.R. 318 http://www.nutricionhospitalaria.com/pdf/6540.pdf}}</ref> Adherence to mucus and human epithelial cells and cell lines and the ability to reduce pathogen adhesion to surfaces is scientifically proven by the research "Influence of Gastrointestinal System Conditions on Adhesion of exopolysaccharide-producing ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' strains to [[Caco-2]] Cells"<ref name=Source29>{{cite journal|last=Darilmaz|first=D|author2=AslımII B |author3=SuludereII Z |author4=Akca G |title=Influence of gastrointestinal system conditions on adhesion of exopolysaccharide-producing ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' strains to caco-2 cells|journal=Braz. Arch. Biol. Technol.|date=2011|volume=54, n.5|issue=5|pages=917–26|doi=10.1590/S1516-89132011000500009|issn=1516-8913|doi-access=free}}</ref>
+Resistance to gastric acid and bile acid are scientifically presented in the following studies where ''L. bulgaricus'' successfully passes through the human intestinal tract, maintaining its viability: “Survival of Yogurt Bacteria in the Human Gut”<ref name=Source27 /> and “''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' Collection to select a strain able to survive to the human intestinal tract.”.<ref name=Source28>{{cite journal|last=Vázquez|first=C|author2=Botella-Carretero, JI |author3=García-Albiach, R |author4=Pozuelo, MJ |author5=Rodríguez-Baños, M |author6=Baquero, F |author7=Baltadjieva, MA |author8= del Campo, R |title=Screening in a ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' collection to select a strain able to survive to the human intestinal tract.|journal=Nutricion Hospitalaria|date=Jul–Aug 2013|volume=28|issue=4|pages=1227–35|doi=10.3305/nh.2013.28.4.6540|pmid=23889646|issn=0212-1611}}</ref> Adherence to mucus and human epithelial cells and cell lines and the ability to reduce pathogen adhesion to surfaces is scientifically proven by the research "Influence of Gastrointestinal System Conditions on Adhesion of exopolysaccharide-producing ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' strains to [[Caco-2]] Cells"<ref name=Source29>{{cite journal|last=Darilmaz|first=D|author2=AslımII B |author3=SuludereII Z |author4=Akca G |title=Influence of gastrointestinal system conditions on adhesion of exopolysaccharide-producing ''Lactobacillus delbrueckii'' subsp. ''bulgaricus'' strains to caco-2 cells|journal=Braz. Arch. Biol. Technol.|date=2011|volume=54, n.5|issue=5|pages=917–26|doi=10.1590/S1516-89132011000500009|issn=1516-8913|doi-access=free}}</ref>
-There are also numerous studies that outline the antimicrobial activity of ''L. bulgaricus'' against potentially pathogenic bacteria such as ''E. Coli'',<ref name=Source24 /> ''Salmonella'' sp.,<ref name=Source24 /> ''S. aureus'',<ref name=Source24 /> ''V. cholera'',<ref name=Source24 /> ''B. subtilis'',<ref name=Source24 /> ''C. difficile''<ref name=Source19 /> and others.
+There are also numerous studies that outline the antimicrobial activity of ''L. bulgaricus'' against potentially pathogenic bacteria such as ''E. Coli'',<ref name="Source242"/> ''Salmonella'' sp.,<ref name="Source242"/> ''S. aureus'',<ref name="Source242"/> ''V. cholera'',<ref name="Source242"/> ''B. subtilis'',<ref name="Source242"/> ''C. difficile''<ref name=Source19 /> and others.
-Thus, the ''L. bulgaricus'' meets all the criteria of the FDA probiotic guideline, with scientific evidence supporting the [[Strain (biology)|strain]] as the clearest example of a safe and effective probiotic food supplement.
 ==References==