In vitro and clinical studies have associated the effectiveness of the Lactobacillus rhamnosus, LGG®, Lactobacillus paracasei, L. CASEI 431® and Bifidobacterium, BB-12® strains (hereafter referred to by use of the trademarks LGG®, L. CASEI 431® and BB-12®) with healthy immune responses. Randomized, double-blinded, placebo-controlled trials suggest that the strains (alone or in combination) may have significant effects on endpoints such as promoting the immune response, and reducing incidence, duration and severity of respiratory tract infections and flu-like symptoms in children and adults.1, 2, 3, 4, 5
Probiotics may help support immune defense
How to help support respiratory tract health:
|Strain:||Lactobacillus rhamnosus, LGG®1|
|Potency:||1 billion CFU/day1|
How to help support respiratory tract health:
|Strain:||Bifidobacterium, BB-12® & Lactobacillus rhamnosus, LGG®2|
|Potency:||1 billion CFU/day, of each strain2|
How to help promote healthy immune response:
|Strain:||Lactobacillus paracasei, L. CASEI 431®3, 4, 5|
|Potency:||1 billion CFU/day3, 4, 5|
|Duration:||2 weeks prior to and during periods with increased exposure, such as influenza season3, 4, 5|
How to help promote healthy immune response:
|Potency:||1 billion CFU/day3|
|Duration:||2 weeks prior to and during periods with increased exposure, such as influenza season3|
Both innate immune responses (such as type 1 interferon [IFN] responses) and adaptive immune responses (such as type 1 T helper cell [Th1] responses) are critical for host defense against bacterial and viral infections.6, 7
Respiratory and flu-like symptoms
Respiratory and flu-like sickness is a wide-ranging category and includes a fever of at least 100°F (37.8°C) and a cough or sore throat. A 2018 study reported that over the previous five years, the average number of symptomatic cases in the US has been 33 million/year.8 Respiratory and flu-like sickness poses a substantial burden on families and societies due to the costs associated with doctor consultations, medicine prescriptions and loss of productivity.9
Since effective antiviral therapies are not available for most respiratory and flu-like sickness, other therapies are needed to help support defense against respiratory tract infections and to decrease symptom load. Therapies supporting proper immune function could serve this purpose.
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The immune response to viruses and bacteria may be promoted with probiotics
The Chr. Hansen L. CASEI 431®, BB-12® and LGG® strains have all been extensively studied in vitro. Data suggest that the strains help trigger a Th1-mediated immune response, both by stimulating INF-γ to induce the maturation of Th1 cells, and by stimulating secretion of proteins such as IL-12, IL-2 and IL-6 cytokines. These are needed for further inducing the production of antibodies that are required to fight invading pathogens.10, 11, 12, 13, 14, 15, 16
Probiotics have in clinical studies been suggested to promote a healthy immune response
Randomized, double-blinded, placebo-controlled studies have investigated the immune modulating effects of the LGG®, L. CASEI 431® and BB-12® strains in children and adults. A widely used model for testing the ability of the immune system to respond to a challenge, such as a viral or bacterial infection, is the vaccine model. In such a model, attenuated viruses are used to challenge the immune system. An integral part of the specific immune response, for example towards viruses and bacteria, is the production of antibodies. Using healthy test participants, measuring the quantity and speed at which the body produces antibodies in plasma and saliva following a vaccine challenge is identified as a highly suitable method of investigating potential ways to promote a healthy immune response.17 By implementing the vaccine model, studies that have supplemented participants with the LGG®, L. CASEI 431® and/or BB-12® strains prior to a vaccine challenge, have demonstrated significant increases in the immune response to the vaccine challenge compared to placebo.3, 4, 5, 18 In addition, the strains have been associated with lower incidence of respiratory and flu-like sickness.2, 19, 20, 21, 22, 23
LGG® and the immune response
Daily intake of LGG® at 1 billion CFU over a 3 month period1 or for the length of a hospital stay19 was associated with a significant reduction in the number of children with upper respiratory tract infections,1 the number of respiratory tract infections lasting longer than three days,1,19 the duration of respiratory symptoms,1 and the number of gastrointestinal infections lasting more than two days.19 Children supplemented with LGG® also had significantly fewer days away from daycare due to illness, compared to the placebo group.1
In a healthy adult population, intake of 10 billion CFU/day of the LGG® strain prior to a vaccine challenge led to an increase in vaccine specific antibodies.18 29% more participants attained a level of specific antibodies that is associated with increased protection than those in the placebo group. This suggests a stronger immune response and increased number of antibodies available to fight the simulated vaccine challenge.18
BB-12® may support immune function
In a randomized, double-blinded, placebo-controlled vaccine model, 1 billion CFU/day of the BB-12® strain were consumed two weeks before a vaccine challenge, and for four weeks after.3 During this time a significant increase in vaccine specific antibodies were found in the BB-12® group compared to the placebo group. This suggests the BB-12® strain is able to improve immune function and augment the systemic response to a bacterial or viral challenge.3
When consumed together, the LGG® and BB-12® strains (each at 1 billion CFU/day) have been associated with fewer days with upper respiratory tract infection symptoms.2 Following a 12-week intervention period in a study of college students, those who received the two-strain combination had 33% fewer days with symptoms and rated their symptoms as significantly less severe, compared to those receiving placebo.2
L. CASEI 431® and the clinical support
Several studies have associated the L. CASEI 431® strain with healthy immune response to vaccine challenges. Three randomized, double-blinded, placebo-controlled studies administered the L. CASEI 431® strain to healthy adults prior to a vaccine challenge. The potency was 1 billion CFU/day in two of the studies3, 4 and 10 billion CFU/day in the third study.5 In all three studies, the group taking the L. CASEI 431® strain had an improved immune response and an increase in vaccine specific antibodies compared to the placebo group.3, 4, 5
One of the largest randomized, clinical probiotic studies to be conducted investigated the effect of the L. CASEI 431® strain on immune response to a vaccine challenge and incidence of upper respiratory tract infections among healthy adults. n=1104 volunteers received 1 billion CFU/day of the strain for 42 days. Following the intervention, the duration of upper respiratory tract infections was significantly reduced in the L. CASEI 431® group compared to placebo. No differences were seen in the number of vaccine specific antibodies.23
LGG®, L. CASEI® and BB-12® may play an important role in immune response support
In preclinical investigations, the LGG®, L. CASEI® and BB-12® probiotic strains have all been associated with capacity to promote a healthy immune response to a challenge. The probiotic strains were associated with a promotion of several steps in the Th1 response required for the formation of specific pathogen-fighting antibodies. This effect on immune function has been supported in clinical studies in which the probiotic strains, some alone and some in combination, have been associated with a reduction in the incidence, duration and severity of respiratory and flu-like sickness.
Read what to look for when choosing a probiotic.
L. CASEI®, LGG® and BB-12® are registered trademarks of Chr. Hansen A/S.
The article is provided for informational purposes regarding probiotics and is not meant to suggest that any substance referenced in the article is intended to diagnose, cure, mitigate, treat, or prevent any disease.
The probiotic strain Lactobacillus paracasei, L. CASEI 431® has demonstrated improvements to immune health in high-quality, human clinical studies.
L. CASEI 431® is a trademark of Chr. Hansen A/S
Lactobacillus rhamnosus, LGG® is the world’s most documented probiotic strain. The LGG® strain has proven benefits across all ages and numerous health areas, including gastrointestinal, immune and oral health.
LGG® is a registered trademark of Chr. Hansen A/S
The probiotic strain Bifidobacterium, BB-12® is the world’s most documented probiotic bifidobacterium. It has been extensively studied and has been associated with improved outcomes across various health areas.
BB-12® is a trademark of Chr. Hansen A/S
1. Hojsak I, et al. Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2010;29(3):312-6. (PubMed)
2. Smith TJ, et al. Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections. The British journal of nutrition. 2013;109(11):1999-2007. (PubMed)
3. Rizzardini G, et al. Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br J Nutr. 2012;107(6):876-84. (PubMed)
4. Trachootham D, et al. Drinking fermented milk containing Lactobacillus paracasei 431 (IMULUS™) improves immune response against H1N1 and cross-reactive H3N2 viruses after influenza vaccination: A pilot randomized triple-blinded placebo controlled trial. J Funct Foods. 2017;33:1-10. (Source)
5. de Vrese M, et al. Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination. Eur J Nutr. 2005;44(7):406-13. (PubMed)
6. Haller O, et al. The interferon response circuit: induction and suppression by pathogenic viruses. Virology. 2006;344(1):119-30. (PubMed)
7. Swain SL, et al. Expanding roles for CD4(+) T cells in immunity to viruses. Nat Rev Immunol. 2012;12(2):136-48. (PubMed)
8. Biggerstaff M, et al. Systematic Assessment of Multiple Routine and Near Real-Time Indicators to Classify the Severity of Influenza Seasons and Pandemics in the United States, 2003-2004 Through 2015-2016. Am J Epidemiol. 2018;187(5):1040-50. (PubMed)
9. Putri WCWS, et al. Economic burden of seasonal influenza in the United States. Vaccine. 2018;36(27):3960-6. (PubMed)
10. Lopez P, et al. Distinct Bifidobacterium strains drive different immune responses in vitro. Int J Food Microbiol. 2010;138(1-2):157-65. (PubMed)
11. Miettinen M, et al. Lactobacilli and streptococci induce interleukin-12 (IL-12), IL-18, and gamma interferon production in human peripheral blood mononuclear cells. Infect Immun. 1998;66(12):6058-62. (PubMed)
12. Miettinen M, et al. Nonpathogenic Lactobacillus rhamnosus activates the inflammasome and antiviral responses in human macrophages. Gut Microbes. 2012;3(6):510-22. (PubMed)
13. Dong H, et al. Comparative effects of six probiotic strains on immune function in vitro. Br J Nutr. 2012;108(3):459-70. (PubMed)
14. Rocha-Ramírez LM, et al. Probiotic Lactobacillus Strains Stimulate the Inflammatory Response and Activate Human Macrophages. J Immunol Res. 2017;2017:4607491-. (PubMed)
15. Chr. Hansen. Internal data on file.
16. Latvala S, et al. Potentially probiotic bacteria induce efficient maturation but differential cytokine production in human monocyte-derived dendritic cells. World J Gastroenterol. 2008;14(36):5570-82. (PubMed)
17. Albers R, et al. Markers to measure immunomodulation in human nutrition intervention studies. Br J Nutr. 2005;94(3):452-81. (PubMed)
18. Davidson LE, et al. Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial. Eur J Clin Nutr. 2011;65(4):501-7. (PubMed)
19. Hojsak I, et al. Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections. Pediatrics. 2010;125(5):e1171-7. (PubMed)
20. Taipale T, et al. Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in infancy. Br J Nutr. 2011;105(3):409-16. (PubMed)
21. Taipale TJ, et al. Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in early childhood. Pediatr Res. 2016;79(1-1):65-9. (PubMed)
22. Hatakka K, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ. 2001;322(7298):1327. (PubMed)
23. Jespersen L, et al. Effect of Lactobacillus paracasei subsp. paracasei, L. casei 431 on immune response to influenza vaccination and upper respiratory tract infections in healthy adult volunteers: a randomized, double-blind, placebo-controlled, parallel-group study. Am J Clin Nutr. 2015;101(6):1188-96. (PubMed)
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