ReviewThe influence of the intestinal microbiome on vaccine responses☆
Introduction
There is substantial variation between individuals in the immune response to vaccinations. The serological response to hepatitis B vaccine, for example, varies more than 100-fold at seven months of age and some infants do not have any measurable antibodies [1], [2]. Similarly, the response to pneumococcal and Hib vaccination at six months of age varies up to 40-fold [1]. This has implications for both protective efficacy and duration of protection. Factors contributing to the variation in vaccine response include age [3], [4], [5], gender [6], genetics [7], [8], [9], geographic location [10], time of day vaccine administered [11] and co-administered vaccines [12], [13]. A further important factor which likely influences vaccine responses is the intestinal microbiome.
In recent years, considerable research has revealed the importance of the intestinal microbiome in the development of the immune system and regulation of immune responses [14], [15]. Abundance of certain bacteria in the intestinal microbiome have been linked to susceptibility to neonatal sepsis [16], chronic inflammatory bowel disease [17], chronic obstructive pulmonary disease [18], diabetes mellitus [19], and eczema, allergies and asthma [20]. Advances in DNA sequencing technology and bioinformatic analysis have facilitated the ability to determine differences in the composition of the intestinal microbiome. Despite the evidence for the intimate relationship between the intestinal microbiome and the immune system, only a limited numbers of studies have investigated the effect of the composition of the intestinal microbiome on vaccine responses. These studies are summarised in this review.
Section snippets
Systematic review methods
In April 2017, MEDLINE (1946 to present) and Embase (1947 to present) were searched using the Ovid interface with the following search terms: (microbiome OR microbiota OR biodiversity OR Actinobacteria OR bacteroides OR Bifidobacterium OR Enterobacteriaceae OR lactobacillus OR Proteobacteria) AND (feces OR faeces OR meconium OR intestin* OR) AND (RNA, ribosomal OR sequence analysis, DNA OR culture or quantif∗) AND (vaccin∗ OR immuniz* OR immunis* OR antibodies OR immunoglobulin OR immunity,
Systematic review results
Three studies reporting results from 146 infants (206 stool samples) and one study reporting results from 17 adults (170 stool samples) met the inclusion criteria (Table 1). Two of the studies were done in developing countries [21], [22]. Responses to oral vaccinations were investigated in two studies [22], [23], to parenteral vaccination in one [24], and to both oral and parenteral in one [21]. Two studies measured humoral and cellular responses in serum [21], [23], while one study each
Discussion
Despite the increasing recognition of the influence of the microbiome on immunity, to date, only three studies that included a total of 146 infants and one study of 17 adults have investigated the influence of the composition of the intestinal microbiome on vaccine responses. These studies show that, in infants, a higher relative abundance of the phylum Actinobacteria (order Actinomycetales, family Coriobacteriaceae, genera Corynebacterium and Rothia, and especially the species B. longum) is
Conclusion
The studies included in this review support the notion that the intestinal microbiome influences vaccine responses, especially early in life. Further well-designed studies determining the influence of the intestinal microbiome, including the influence of viruses, fungi and parasites, on vaccine responses are needed. This will help identify strategies, such nutritional interventions, to improve vaccine efficacy and duration of protection, particularly in infancy when the intestinal microbiome is
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Availability of data and material
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Funding
PZ is supported by a Fellowship from the European Society of Paediatric Infectious Diseases and an International Research Scholarship from the University of Melbourne.
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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Once sentence summary: The relative abundance of certain bacterial taxa in the intestinal microbiome influences both humoral and cellular immune responses to oral and parenteral vaccines.