ReviewThe influence of probiotics on vaccine responses – A systematic review
Introduction
The immune response to vaccinations varies substantially between individuals. This has implications for both protective efficacy and duration of protection. Factors contributing to the variation in vaccine responses include age [1], [2], [3], gender [4], genetics [5], [6], [7], geographic location [8], time of day vaccine administered [9], and co-administered vaccines [10], [11].
In recent years, considerable research has revealed the importance of the intestinal microbiota in the development of the immune system and regulation of immune responses [12], [13]. While there have been only few studies on the effect of the intestinal microbiota on vaccine responses [14], [15], [16], [17], [18], many studies have investigated the effect of probiotics around the time of vaccination.
Probiotics are defined as live microorgansims which, when administered orally in adequate amounts (thought to be ≥ 1 × 109 colony forming units (cfu) daily), are beneficial to the host [19]. The most frequently used microorgansims are Lactobacillus spp, Bifidobacterium spp, and Saccharomyces boulardii. The mechanism of action of probiotics include normalisation of perturbed microbiota, regulation of intestinal transit, increased turnover of enterocytes, gut barrier reinforcement, colonisation resistance, acid and short-chain fatty acid production, vitamin synthesis, and bile salt metabolism [19]. Probiotics enhance both innate and adaptive immunity [20], [21], and have been found to be beneficial in treatment of acute gastroenteritis [22], [23], in prevention of antibiotic-associated diarrhoea [24], in reduction of infection in children attending day care centres [25], [26], [27], and in prevention of eczema and allergies [28], [29]. However, most studies investigating the influence of probiotics on the immune response in humans have been small in size or limited. Despite this, there has been an explosion in the use of probiotics, promoted by the pharmaceutical industry; the global probiotics market size exceeded US$35 billion in 2015. An evidence base to guide interventions is critically needed. Here, we systematically review studies investigating the influence of probiotics on vaccine responses.
Section snippets
Systematic search method
In April 2017, MEDLINE (1946 to present) and Embase (1947 to present) were searched using the Ovid interface with the following search terms: (probiotics OR Lactobacillus OR Bifidobacterium) AND (vaccin∗ OR immun∗ OR antibod∗ OR humoral) without any language limitations. This identified 2366 studies. Of these, 25 fulfilled our inclusion criteria of prospective randomised placebo-controlled studies in humans measuring humoral vaccines responses in plasma or stool after administration of
Results
A total of 26 studies were reviewed, involving 3812 participants, investigating the use of 40 different probiotic strains on the efficacy of 17 different vaccines (DTP (2), DTwP, DTaP-Hib (2), DTaP-IPV-Hib (2), HAV, HBV (2), Hib, LAIV, MMRV, OCV (2), OPV, ORV, PCV7, PPV23 (2), Polio, TIV (11), Ty21a). The dose of probiotic used in each study varied between 108 and 1013 colony forming units cfu per day.
Discussion
In our systematic review of the studies that have reported the effect of probiotics on the humoral response to either parenteral or oral vaccinations, a beneficial effect was reported in about half (in 3 of 7 studies investigating parental vaccinations in neonates and children [18], [33], [37], in 5 of 12 investigating responses to influenza vaccination [43], [45], [46], [48], [49], in the one study investigation response to hepatitis A vaccination [55], and in 3 of 5 studies assessing oral
Acknowledgement
PZ was supported by a International Research Scholarship from the University of Melbourne and a Scholarship from the Ettore-Rossi-Foundation.
Competing interests
The authors declare that they have no competing interests.
Conflict of interest
The authors declare no conflict of interest.
Authors’ contributions
PZ drafted the initial manuscript, and approved the final manuscript as submitted. NC critically reviewed and revised the manuscript, and approved the final manuscript as submitted.
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