Vaccine Efficacy, Part 2 of 2: Can a Healthy Gut Microbiome Improve It?
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The influence of probiotics on the immune response
Vaccines are among the greatest successes of modern medicine, helping to protect entire populations against a wide range of infectious diseases. However, there is considerable variation in the efficacy of vaccines amongst individuals. The magnitude of antibody titers induced in individuals receiving the seasonal influenza vaccine, for example, varies by more than 100-fold.
Inadequate vaccine responses can leave people unknowingly susceptible to new infections even if they are immunized, and may also compromise the achievement of herd immunity in the population.
One factor that influences vaccine efficacy is the human gut microbiome (the large collection of microbes that inhabit the gut).,,, A diverse microbial community, dominated by beneficial bacterial species, supports the health of both the gut and the immune system.,, A healthy microbiota influences the immune system directly via contact between gut microbes and gut-associated immune cells,, as well as indirectly through the production of short-chain fatty acids (SCFAs) and other essential nutrients that impact immunity.,
The primary factor influencing the gut microbiota is the diet. The consumption of high-fiber diets and fermented foods, for example, has been shown to significantly improve the health of the microbial community.,,, In the first part of this article we discussed how fiber-rich diets encourage the growth of beneficial bacteria that support the immune response. Today, we’ll focus on the influence of friendly microorganisms, many of which are commonly found in the gut or dietary supplements known as probiotics, on the gut and immune system.
The microbiota in health and disease
An imbalance in the gut microbial community may be a major factor in the variable efficacy of vaccines.
Studies show that an imbalance in the gut microbial community, known as dysbiosis, may be a major factor in the variable efficacy of vaccines.,, Dysbiosis is generally characterized by a loss of beneficial species, a reduction in microbial diversity, and an increase in potential pathogens.,
Unfortunately, dysbiosis is all too common. Low-fiber diets contribute to this condition,,, as do endocrine disruptors in the environment. Chronic conditions such as obesity, diabetes, irritable bowel syndrome, and aging itself are all associated with a decline in health of the microbial community., Additionally, the use of medications such as antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (commonly used for heartburn) can cause a reduction in beneficial microbes.,
It’s especially difficult to avoid the harmful effects of antibiotics, because most of us receive them multiple times throughout life., A single course of antibiotics can destroy more than 90% of the predominant types of microbes in the gut, including friendly bifidobacteria.,,, Although many are aware of the acute gastrointestinal side effects of antibiotic use, we neglect to consider the long-term impact they have. Studies have shown it can take up six months for the microbiota to fully recover.,,,
Fortunately, supplementation with probiotic microorganisms can help reduce the negative effects of antibiotics, particularly if the probiotics are consumed beginning on the first day of antibiotic treatment.,, In particular, the probiotic known as Saccharomyces boulardii, discussed at length momentarily, is an excellent selection for use alongside an antibiotic because it is a yeast, and thus able to survive the antibiotic bacterial killing powers. By preventing dysbiosis, probiotics can also improve vaccine responses, as discussed below.
The importance of Lactobacillus
Animal and human studies have shown that the administration of L. rhamnosus can improve the antibody response to common vaccines.
The most extensively-studied bacterial probiotics are Lactobacillus and Bifidobacterium species. Lactobacilli are found in many fermented foods, including yogurt and kefir. Once they are consumed, they reside mainly in the small intestine, while bifidobacteria are found mainly in the colon.,,
People who consume a standard Western diet consisting of highly-processed foods generally have low numbers of lactobacilli, while higher levels are generally found in individuals consuming plant-based diets, fermented foods, or probiotics.,,,
Lactobacillus species display many important features including the ability to enhance both innate (non-specific) and adaptive (specific) immunity. In a remarkable display of this principle, scientists showed that the ingestion of a single dose of a strain of lactobacillus known as L. rhamnosus GG turned on genes related to B cell activation within two hours in healthy volunteers. B cells are responsible for producing antigen-specific antibodies in response to vaccines, and the study shows that L. rhamnosus GG directly impacts this response. Although the probiotic dose used in this study was particularly high, at 885 billion colony-forming units (CFUs), the authors note that a follow-up study with continuous more typical dosing would offer further insights to how the body responds to these friendly bacteria.
Consistent with these findings, animal and human studies have shown that the administration of L. rhamnosus can improve the antibody response to common vaccines as well., In a placebo-controlled study of influenza vaccination, 84% of healthy subjects receiving L. rhamnosus GG developed a level of antibodies considered to be adequate for protection against the H3N2 influenza strain within 28 days after vaccination, versus only 55% of those in the placebo group.
Lactobacillus probiotics have been shown stimulate the production of interleukin (IL)-12, a cytokine messenger associated with the Th1 immune response, which is important for a healthy response against viruses.,, There are many different Lactobacillus species, which each activate multiple immune-related pathways.,, Many Lactobacillus species promote the maturation of dendritic cells, a type of white blood cell that potentiates the immunologic reaction to vaccines.,,
For all these reasons, lactobacilli are even being considered by the pharmaceutical industry as possible adjuvants for vaccines. In addition to the research with L. rhamnosus GG, numerous studies suggest other common lactobacillus probiotic species have a beneficial impact on vaccine response when consumed on a daily basis, either before or after immunization.,,,, In placebo-controlled trials, improved responses (antibody titers) to common vaccines have been seen with L. rhamnosus, L. casei, L. fermentum, L. acidophilus, and L. plantarum.,,,,,,,
New developments also suggest that the effects of lactobacilli may not depend on the presence of living bacteria. A heat-killed L. casei strain, for example, was shown to enhance the response to an influenza vaccine in mice. Inactivated probiotics (known as immunobiotics or paraprobiotics) are of great interest because they are far more stable than live microbes and also are safer in immunocompromised populations.
The importance of Bifidobacterium
Gut levels of bifidobacteria often correlate with immune responses to vaccines.
Whereas lactobacilli live in the small intestine, bifidobacteria reside in the colon, where the vast majority of the gut microbiota are found. Bifidobacteria normally represent 8-10% of the gut microbiota but a single dose of antibiotic can destroy almost 100% of the population.,,
One of the many important functions of bifidobacteria is to ferment dietary fibers and produce acetate, a short-chain fatty acid (SCFA) that is used as food by other beneficial bacteria in the colon, helping to restore a more healthful microbial balance overall., SCFAs not only improve gut health, they also support antibody responses.,, In B cells, SCFAs are involved in many metabolic processes that are necessary to produce energy and the building blocks for antibody production.
Another important immune-related job our bifidobacteria serve is to help increase the activity (aka helper recruiting and killing power) of immune cells, including dendritic cells, helper T cells, and natural killer (NK) cells, all of which are needed to mount an effective response to challenges., It’s perhaps not surprising, then, that gut levels of bifidobacteria often correlate with immune responses to vaccines.,, A randomized controlled trial showed that adults who consumed a common strain of bifidobacteria known as B. lactis daily for two weeks before a flu vaccine, and for four weeks after vaccination, had 60% higher vaccine-specific antibody levels compared to a placebo group.
For long-term health, bifidobacteria such as B. lactis, B. bifidum, B. longum and B. breve can be taken in regularly via fermented foods or probiotic supplementation. Dietary supplementation with bifidobacteria also has been shown to help alleviate the dysbiosis associated with aging and antibiotic use.,,
The role of Saccharomyces boulardii
S. boulardii also has been shown to influence the production of IL-12, which enables a strong immune response to infections.
S. boulardii, a yeast originally isolated from tropical fruit, is arguably the best-known probiotic for the prevention of dysbiosis due to antibiotics., The administration of S. boulardii to healthy subjects does not alter their microbiota long-term however, as it is only a transient resident. That said, in the case of dysbiosis, S. boulardii has been shown to possibly restore the intestinal microbiota faster.
S. boulardii is genetically related to baker’s yeast (S. cerevisiae), but it has distinct features leading to its classification as a probiotic., For example, S. boulardii also is capable of increasing SCFA levels,, and S. cerevisiae does not have this property.
Like other yeasts, S. boulardii contains β-glucans, which are known for their immune-modulating effects.,, Remarkably, bifidobacteria can ferment these yeast beta-glucans, which suggests that S. boulardii actually also serves as a prebiotic to encourage the growth of bifidobacteria.
In recent studies, S. boulardii has been shown to synergize with Lactobacillus and Bifidobacterium species.,, Supplementation with a combination of S. boulardii and bifidobacteria spp. was shown to enhance cellular immune functions in a synergistic manner and to reduce the hospital stay in children with severe diarrhea.
In a human clinical trial, supplementation with a nutritional formula containing S. boulardii lysate, colostrum-derived lactoferrin, and several other components, was shown to increase NK cell activity in healthy elderly volunteers. A third of the subjects even showed a doubling of NK cell activity after two months of daily supplementation.
S. boulardii also has been shown to influence the production of IL-12, which enables a strong immune response to infections. The ingestion of S. boulardii was recently shown to increase the efficacy of a novel DNA vaccine in an animal model. The authors observed that the use of S. boulardii as immunomodulator represents a new strategy for more efficient DNA vaccines.
Prebiotics and probiotics have synergistic effects
The probiotics “seed” the microbiota with beneficial bacteria, and the prebiotics “feed” the microbes with the carbohydrates they need to grow.
Prebiotics, which are dietary fibers that can be fermented in the gut, are known to increase bifidobacteria populations.,,, In fact, it is this effect that explains many of the health benefits of prebiotics.
Combinations of prebiotics and probiotics are known as synbiotics due to their synergistic effects., The probiotics “seed” the microbiota with beneficial bacteria, and the prebiotics “feed” the microbes with the carbohydrates they need to grow. Symbiotic combinations have been shown to help correct dysbiosis and enhance immune responses in a variety of clinical settings.,,,
Prebiotic intake may be particularly effective for subjects who have low numbers of bifidobacteria. On the other hand, prebiotics alone may not restore populations of bifidobacteria if they are too severely depleted. Probiotics or synbiotics may be helpful in such cases. A systematic review of clinical trials, comprising nearly 2000 adults, concluded that probiotics and prebiotics may improve antibody responses in adults receiving influenza vaccines.
What to look for in a probiotic supplement
When it comes to choosing a bacterial probiotic supplement, multispecies preparations including Lactobacillus and Bifidobacterium are often preferred over single strains; however, there are some unique strains such as L. rhamnosus GG, discussed herein, which have been widely studied as a monotherapy in many clinical settings.
Cell numbers (as CFUs) are usually printed on the label of probiotic products, and this is important for efficacy. Since there are more than 10 trillion bacteria in the colon, it has been suggested that at least 10 billion viable probiotic microorganisms reaching the bowel may be necessary to provide a significant effect., Studies support the efficacy of high-potency probiotic formulations that provide 50 billion CFU per dose.,Click here to see References
 Vetter V, et al. Understanding modern-day vaccines: what you need to know. Ann Med. 2018 Mar;50(2):110-20.
 Lynn DJ, Pulendran B. The potential of the microbiota to influence vaccine responses. J Leukocyte Biol. 2018 Feb;103(2):225-31.
 Nakaya HI, et al. Systems analysis of immunity to influenza vaccination across multiple years and in diverse populations reveals shared molecular signatures. Immunity. 2015 Dec 15;43(6):1186-98.
 Zimmerman P, Curtis N. Factors that influence the immune response to vaccination. Clin Microbiol Rev. 2019 Mar 13;32(2):e00084-18.
 Ciabattini A, et al. Role of the microbiota in the modulation of vaccine immune responses. Front Microbiol. 2019 Jul 3;10:1305.
 Shelly A, et al. Impact of microbiota: a paradigm for evolving herd immunity against viral diseases. Viruses. 2020 Oct 10;12(10):1150.
 Zimmerman P, Curtis N. The influence of the intestinal microbiome on vaccine responses. Vaccine. 2018 Jul 16;36(30):4433-9.
 Rosenthal KS, Zimmerman DH. Vaccines: all things considered. Clin Vaccine Immunol. 2006 Aug;13(8):821-9.
 Minton K. Microbiota: a ‘natural’ vaccine adjuvant. Nature Rev Immunol. 2014 Sep 19;14(10):650.
 Gagliardi A, et al. Rebuilding the gut microbiota ecosystem. Int J Environ Res Pub Health. 2018 Aug;15(8):1679.
 Oh JZ, et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity. 2014 Sep 18;41(3):478-92.
 Lebeer S, et al. Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nature Rev Microbiol. 2010 Mar;8(3):171-84.
 Shi CW, et al. Effect of Lactobacillus rhamnosus on the development of B cells in gut‐associated lymphoid tissue of BALB/c mice. J Cell Molec Med. 2020 Aug;24(15):8883.
 Rios-Covián D, et al. Intestinal short chain fatty acids and their link with diet and human health. Fron Microbiol. 2016 Feb 17;7:185.
 Corrêa‐Oliveira R, et al. Regulation of immune cell function by short‐chain fatty acids. Clin Translat Immunol. 2016 Apr;5(4):e73.
 Bengmark S. Colonic food: pre- and probiotics. Am J Gastroenterol. 2000 Jan;95(1 Suppl):S5-7.
 Kim DH, et al. Modern perspectives on the health benefits of kefir in next generation sequencing era: improvement of the host gut microbiota. Crit Rev Food Sci Nutr. 2019 Jun 17;59(11):1782-93.
 Chilton SN, et al. Inclusion of fermented foods in food guides around the world. Nutrients. 2015 Jan;7(1):390-404.
 Volokh O, et al. Human gut microbiome response induced by fermented dairy product intake in healthy volunteers. Nutrients. 2019 Mar;11(3):547.
 Veiga P, et al. Changes of the human gut microbiome induced by a fermented milk product. Sci Rep. 2014 Sep 11;4:6328.
 Nadeem S, et al. Gut dysbiosis thwarts the efficacy of vaccine against Mycobacterium tuberculosis. Front Immunol. 2020 May 19;11:726.
 Vlasova AN, et al. How the gut microbiome regulates host immune responses to viral vaccines. Curr Opin Virol. 2019 Aug 1;37:16-25.
 Macbeth J, Hsiao A. A dysbiotic gut microbiome suppresses antibody mediated-protection against Vibrio cholerae. bioRxiv. 2019 Jan 1:730796.
 Hagan T, et al. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell. 2019 Sep 5;178(6):1313-28.
 Antharam VC, et al. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013 Sep 1;51(9):2884-92.
 Redondo-Useros N, et al. Microbiota and lifestyle: a special focus on diet. Nutrients. 2020 Jun;12(6):1776.
 Deehan EC, Walter J. The fiber gap and the disappearing gut microbiome: implications for human nutrition. Trends Endocrinol Metab. 2016 May;27(5):239-42.
 Putignani L, Dallapiccola B. Foodomics as part of the host-microbiota-exposome interplay. J Proteomics. 2016 Sep 16;147:3-20.
 Gálvez-Ontiveros Y, et al. Endocrine disruptors in food: impact on gut microbiota and metabolic diseases. Nutrients. 2020 Apr;12(4):1158.
 De Filippis A, et al. Gastrointestinal disorders and metabolic syndrome: dysbiosis as a key link and common bioactive dietary components useful for their treatment. Int J Mol Sci. 2020 Jan;21(14):4929.
 Li X, et al. Gut microbiota dysbiosis drives and implies novel therapeutic strategies for diabetes mellitus and related metabolic diseases. Front Immunol. 2017 Dec 20;8:1882.
 Wang L, et al. Gut microbial dysbiosis in the irritable bowel syndrome: a systematic review and meta-analysis of case-control studies. J Acad Nutr Dietet. 2020 Apr 1;120(4):565-86.
 Salazar N, et al. Age-associated changes in gut microbiota and dietary components related with the immune system in adulthood and old age: a cross-sectional study. Nutrients. 2019 Aug;11(8):1765.
 Cianci R, et al The interplay between immunosenescence and microbiota in the efficacy of vaccines. Vaccines. 2020 Dec;8(4):636.
 Syer SD, Wallace JL. Environmental and NSAID-enteropathy: dysbiosis as a common factor. Curr Gastroenterol Rep. 2014 Mar 1;16(3):377.
 Bruno G, et al. Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified. World J Gastroenterol. 2019 Jun 14;25(22):2706.
 Grigoryan L, Zoorob R, Shah J, Wang H, Arya M, Trautner BW. Antibiotic prescribing for uncomplicated acute bronchitis is highest in younger adults. Antibiotics. 2017 Dec;6(4):22.
 Centers for Disease Control and Prevention (CDC). Outpatient antibiotic prescriptions — United States, 2016 [Internet]. Atlanta (GA): CDC; 2018 [cited 2021 Jan 14]. Available from: https://www.cdc.gov/antibiotic-use/community/programs-measurement/state-local-activities/outpatient-antibiotic-prescriptions-US-2016.html
 Konstantinidis T, et al. Effects of antibiotics upon the gut microbiome: a review of the literature. Biomedicines. 2020 Nov;8(11):502.
 Buffie CG, et al. Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Infect Immunity. 2012 Jan 1;80(1):62-73.
 Antharam VC, et al. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013 Sep 1;51(9):2884-92.
 Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci. 2011 Mar 15;108(Supplement 1):4554-61.
 Isaac S, et al. Short-and long-term effects of oral vancomycin on the human intestinal microbiota. J Antimicrob Chemother. 2016 Oct 5;72(1):128-36.
 Korpela K, et al. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun. 2016 Jan 26;7:10410.
 Pérez-Cobas AE, et al. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut. 2013 Nov 1;62(11):1591-601.
 Jump RL, et al. Metabolomics analysis identifies intestinal microbiota-derived biomarkers of colonization resistance in clindamycin-treated mice. PLoS One. 2014 Jul 2;9(7):e101267.
 Carstensen JW, et al. Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study. Eur J Clin Microbiol Infect Dis. 2018 Aug 1;37(8):1431-9.
 McFarland LV, et al. Primary prevention of Clostridium difficile infections with a specific probiotic combining Lactobacillus acidophilus, L. casei, and L. rhamnosus strains: assessing the evidence. J Hosp Infect. 2018 Aug 1;99(4):443-52.
 Ouwehand AC, et al. Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study. Vaccine. 2014 Jan 16;32(4):458-63.
 Vaughan EE, et al. Diversity, vitality and activities of intestinal lactic acid bacteria and bifidobacteria assessed by molecular approaches. FEMS Microbiol Rev. 2005 Aug 1;29(3):477-90.
 Walter J. Ecological role of lactobacilli in the gastrointestinal tract: implications for fundamental and biomedical research. Appl Environ Microbiol. 2008 Aug 15;74(16):4985-96.
 Reuter G. The Lactobacillus and Bifidobacterium microflora of the human intestine: composition and succession. Curr Issues Intest Microbiol. 2001 Sep 1;2(2):43-53.
 Derrien M, et al. Fate, activity, and impact of ingested bacteria within the human gut microbiota. Trends Microbiol. 2015 Jun 1;23(6):354-66.
 Passoli E, et al. Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome. Nature Commun. 2020 May 25;11(1):1-2.
 Kok CR, Hutkins R. Yogurt and other fermented foods as sources of health-promoting bacteria. Nutr Rev. 2018 Dec 1;76(Supplement_1):4-15.
 Toscano M, et al. Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: a preliminary study. World J Gastroenterol. 2017 Apr 21;23(15):2696.
 Bornholdt J, et al. Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial. Gut microbes. 2020 Nov 9;12(1):1-4.
 Kandasamy S, et al. Lactobacilli and bifidobacteria enhance mucosal B cell responses and differentially modulate systemic antibody responses to an oral human rotavirus vaccine in a neonatal gnotobiotic pig disease model. Gut Microbes. 2014 Sep 3;5(5):639-51.
 Vlasova AN, et al. Lactobacilli and bifidobacteria promote immune homeostasis by modulating innate immune responses to human rotavirus in neonatal gnotobiotic pigs. PLoS One. 2013 Oct 2;8(10):e76962.
 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 Apr;65(4):501-7.
 Gad M, et al. Regulation of the IL-10/IL-12 axis in human dendritic cells with probiotic bacteria. FEMS Immunol Med Microbiol. 2011 Oct 1;63(1):93-107.
 Kawashima T, et al. Lactobacillus plantarum strain YU from fermented foods activates Th1 and protective immune responses. Int Immunopharmacol. 2011 Dec 1;11(12):2017-24.
 Park MK, et al. Lactobacillus plantarum DK119 as a probiotic confers protection against influenza virus by modulating innate immunity. PLoS One. 2013 Oct 4;8(10):e75368.
 Segers ME, Lebeer S. Towards a better understanding of Lactobacillus rhamnosus GG-host interactions. Microbial Cell Factories. 2014 Aug;13(1):1-16.
 Galdeano CM, Perdigon G. The probiotic bacterium Lactobacillus casei induces activation of the gut mucosal immune system through innate immunity. Clinical and Vaccine Immunology. 2006 Feb 1;13(2):219-26.
 van Baarlen P, et al. Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proc Natl Acad Sci. 2011 Mar 15;108(Supplement 1):4562-9.
 Konstantinov SR, et al. S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc Natl Acad Sci. 2008 Dec 9;105(49):19474-9.
 Fong FL, et al. Immunomodulatory effects of Lactobacillus rhamnosus GG on dendritic cells, macrophages and monocytes from healthy donors. J Funct Foods. 2015 Mar 1;13:71-9.
 Evrard B, et al. Dose-dependent immunomodulation of human dendritic cells by the probiotic Lactobacillus rhamnosus Lcr35. PLoS One. 2011 Apr 18;6(4):e18735.
 Bumgardner SA, et al. Nod2 is required for antigen-specific humoral responses against antigens orally delivered using a recombinant Lactobacillus vaccine platform. PLoS One. 2018 May 7;13(5):e0196950.
 Dhakal S, Klein SL. Host factors impact vaccine efficacy: implications for seasonal and universal influenza vaccine programs. J Virol. 2019 Nov 1;93(21):e00797-19.
 Bosch M, et al. Lactobacillus plantarum CECT7315 and CECT7316 stimulate immunoglobulin production after influenza vaccination in elderly. Nutricion Hospitalaria. 2012;27(2):504-9.
 Boge T, et al. A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials. Vaccine. 2009 Sep 18;27(41):5677-84.
 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. Brit J Nutr. 2012 Mar;107(6):876-84.
 Link-Amster H, et al. Modulation of a specific humoral immune response and changes in intestinal flora mediated through fermented milk intake. FEMS Immunol Med Microbiol. 1994 Nov 1;10(1):55-63.
 De Vrese M, et al. Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination. Eur J Nutr. 2005 Oct 1;44(7):406-13.
 Isolauri E, et al. Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine. 1995 Jan 1;13(3):310-2.
 Olivares M, et al. Oral intake of Lactobacillus fermentum CECT5716 enhances the effects of influenza vaccination. Nutrition. 2007 Mar 1;23(3):254-60.
 Jung YJ, et al. Adjuvant effects of killed Lactobacillus casei DK128 on enhancing T helper type 1 immune responses and the efficacy of influenza vaccination in normal and CD4-deficient mice. Vaccine. 2020 Aug 10;38(36):5783-92.
 Sender R, et al. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016 Aug 19;14(8):e1002533.
 Woodmansey EJ, et al. Comparison of compositions and metabolic activities of fecal microbiotas in young adults and in antibiotic-treated and non-antibiotic-treated elderly subjects. Appl Environ Microbiol. 2004 Oct 1;70(10):6113-22.
 Bartosch S, et al. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol. 2004 Jun 1;70(6):3575-81.
 Mangin I, et al. Long-term changes in human colonic Bifidobacterium populations induced by a 5-day oral amoxicillin-clavulanic acid treatment. PLoS One. 2012 Nov 27;7(11):e50257.
 Fukuda S, et al. Acetate-producing bifidobacteria protect the host from enteropathogenic infection via carbohydrate transporters. Gut Microbes. 2012 Sep 20;3(5):449-54.
 Rivière A, et al. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Front Microbiol. 2016 Jun 28;7:979.
 Smith PM, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013 Aug 2;341(6145):569-73.
 Furusawa Y, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013 Dec;504(7480):446-50.
 Alessandri G, et al. Bifidobacterial dialogue with its human host and consequent modulation of the immune system. Front Immunol. 2019;10:2348.
 Kim M, et al. Gut microbial metabolites fuel host antibody responses. Cell Host Microbe. 2016 Aug 10;20(2):202-14.
 Gill HS, et al. Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes. J Clin Immunol. 2001 Jul 1;21(4):264-71.
 Miller LE, et al. The effect of Bifidobacterium animalis ssp. lactis HN019 on cellular immune function in healthy elderly subjects: systematic review and meta-Analysis. Nutrients. 2017 Mar;9(3):191.
 Huda MN, et al. Stool microbiota and vaccine responses of infants. Pediatrics. 2014 Aug 1;134(2):e362-72.
 Zhang Q, et al. Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection. Genome Biol. 2020 Dec;21(1):1-26.
 Sadiq FA. Is it time for microbiome-based therapies in viral infections? Virus Res. 2020 Oct 22:198203.
 Bajaj BK, et al. Functional mechanisms of probiotics. J Microbiol Biotechnol Food Sci. 2020 Jan 12;2020:321-7.
 Ruiz L, et al. Bifidobacteria and their molecular communication with the immune system. Front Microbiol. 2017 Dec 4;8:2345.
 Ahmed M, et al. Impact of consumption of different levels of Bifidobacterium lactis HN019 on the intestinal microflora of elderly human subjects. J Nutr Health Aging. 2007 Jan 1;11(1):26.
 Gargari G, et al. Consumption of a Bifidobacterium bifidum strain for 4 weeks modulates dominant intestinal bacterial taxa and fecal butyrate in healthy adults. Applied and environmental microbiology. 2016 Oct 1;82(19):5850-9.
 Moré MI, Swidsinski A. Saccharomyces boulardii CNCM I-745 supports regeneration of the intestinal microbiota after diarrheic dysbiosis-a review. Clin Exper Gastroenterol. 2015;8:237.
 Kabbani TA, et al. Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers. Gut Microbes. 2017 Jan 2;8(1):17-32.
 Czerucka D, Rampal P. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. World Gastroenterol. 2019 May 14;25(18):2188.
 Edwards-Ingram L, et al. Genotypic and physiological characterization of Saccharomyces boulardii, the probiotic strain of Saccharomyces cerevisiae. Appl Environ Microbiol. 2007 Apr 15;73(8):2458-67.
 Smith IM, et al. Yeast modulation of human dendritic cell cytokine secretion: an in vitro study. PloS one. 2014 May 9;9(5):e96595.
 Pais P, et al. Saccharomyces boulardii: what Makes It Tick as Successful Probiotic?. J Fungi. 2020 Jun;6(2):78.
 Schneider SM, et al. Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition. World J Gastroenterol. 2005 Oct 21;11(39):6165.
 Girard-Pipau F, et al. Intestinal microflora, short chain and cellular fatty acids, influence of a probiotic Saccharomyces boulardii. Microb Ecol Health Dis. 2002 Jan 1;14(4):221-8.
 Offei B, et al. Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast Saccharomyces cerevisiae var. boulardii. Genome Res. 2019 Sep 1;29(9):1478-94.
 Bohn JA, BeMiller JN. (1→ 3)-β-d-Glucans as biological response modifiers: a review of structure-functional activity relationships. Carb Polymers. 1995 Jan 1;28(1):3-14.
 Stier H, et al. Immune-modulatory effects of dietary yeast beta-1, 3/1, 6-D-glucan. Nutr J. 2014 Dec 1;13(1):38.
 Keung HY, et al. Mechanistic study of utilization of water-insoluble Saccharomyces cerevisiae glucans by Bifidobacterium breve strain JCM1192. Appl Environ Microbiol. 2017 Apr 1;83(7).
 Moens F, et al. Lactobacillus rhamnosus GG and Saccharomyces cerevisiae boulardii exert synergistic antipathogenic activity in vitro against enterotoxigenic Escherichia coli. Benef Microbes. 2019 Dec 9;10(8):923-35.
 Dinleyici EC, et al. Saccharomyces boulardii CNCM I-745 reduces the duration of diarrhoea, length of emergency care and hospital stay in children with acute diarrhoea. Beneficial Microbes. 2015 Aug 1;6(4):415-21.
 Wang G, Feng D. Therapeutic effect of Saccharomyces boulardii combined with Bifidobacterium and on cellular immune function in children with acute diarrhea. Exp Ther Med. 2019 Oct 1;18(4):2653-9.
 Naito Y, et al. Gut-targeted immunonutrition boosting natural killer cell activity using Saccharomyces boulardii lysates in immuno-compromised healthy elderly subjects. Rejuv Res. 2014 Apr 1;17(2):184-7.
 Silveira MM, et al. Saccharomyces boulardii improves humoral immune response to DNA vaccines against leptospirosis. J Med Microbiol. 2017 Feb 1;66(2):184-90.
 Brokaert WF, et al. Prebiotic and other health-related effects of cereal-derived arabinoxylans, arabinoxylan-oligosaccharides, and xylooligosaccharides. Crit Rev Food Sci Nutr. 2011 Jan 31;51(2):178-94.
 Davis LM, et al. Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans. PLoS One. 2011 Sep 26;6(9):e25200.
 Monteagudo-Mera A, et al. High purity galacto-oligosaccharides (GOS) enhance specific Bifidobacterium species and their metabolic activity in the mouse gut microbiome. Benef Microbes. 2016;7(2):247.
 Vulevic J, et al. Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons. Brit J Nutr. 2015 Aug;114(4):586-95.
 Bartosch S, et al. Microbiological effects of consuming a synbiotic containing Bifidobacterium bifidum, Bifidobacterium lactis, and oligofructose in elderly persons, determined by real-time polymerase chain reaction and counting of viable bacteria. Clin Infect Dis. 2005 Jan 1;40(1):28-37.
 Childs CE, et al. Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study. Brit J Nutr. 2014 Jun;111(11):1945-56.
 Shimizu K, et al. Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: a randomized controlled trial. Crit Care. 2018 Dec 1;22(1):239.
 Valentini NH, et al. Effects of synbiotic supplementation on gut functioning and systemic inflammation of community-dwelling elders – secondary analyses from a randomized clinical trial. Arquivos Gastroenterol. 2020 (ePub ahead of print).
 Anzawa D, et al. Effects of synbiotics containing Bifidobacterium animalis subsp. lactis GCL2505 and inulin on intestinal bifidobacteria: a randomized, placebo‐controlled, crossover study. Food Sci Nutr. 2019 May;7(5):1828-37.
 Lépine A, de Vos P. Synbiotic effects of the dietary fiber long‐chain inulin and probiotic lactobacillus acidophilus W37 can be caused by direct, synergistic stimulation of immune toll‐like receptors and dendritic cells. Mol Nutr Food Res. 2018 Aug;62(15):1800251.
 De Preter V, et al. Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects. Aliment Pharmacol Ther. 2008 Mar;27(6):504-13.
 Tao C, Zeng W, Zhang Q, Liu G, Wu F, Shen H, Zhang W, Bo H, Shao H. Effects of the prebiotic inulin‐type fructans on post‐antibiotic reconstitution of the gut microbiome. J Appl Microbiol. 2020 Aug 19.
 Lei WT, et al. Effect of probiotics and prebiotics on immune response to influenza vaccination in adults: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2017 Nov;9(11):1175.
 McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006 Apr;101(4):812-22.
 Forssten S, Ouwehand AC. Dose-response recovery of probiotic strains in simulated gastro-intestinal passage. Microorganisms. 2020 Jan 13;8(1):112.
 Gao XW, et al. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients.
 Maziade PJ, et al. A Decade of experience in primary prevention of Clostridium difficile infection at a community hospital using the probiotic combination Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+). Clin Infect Dis. 2015 May 15;60 Suppl 2:S144-7.
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Marina MacDonald, MS, PhD
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