Adjuvant Probiotics and the Intestinal Microbiome: Enhancing Vaccines and Immunotherapy Outcomes

Abstract

Immune defence against pathogenic agents comprises the basic premise for the administration of vaccines. Vaccinations have hence prevented millions of infectious illnesses, hospitalizations and mortality. Acquired immunity comprises antibody and cell mediated responses and is characterized by its specificity and memory. Along a similar congruent yet diverse mode of disease prevention, the human host has negotiated from in utero and at birth with the intestinal commensal bacterial cohort to maintain local homeostasis in order to achieve immunological tolerance in the new born. The advent of the Human Microbiome Project has redefined an appreciation of the interactions between the host and bacteria in the intestines from one of a collection of toxic waste to one of a symbiotic existence. Probiotics comprise bacterial genera thought to provide a health benefit to the host. The intestinal microbiota has profound effects on local and extra-intestinal end organ physiology. As such, we further posit that the adjuvant administration of dedicated probiotic formulations can encourage the intestinal commensal cohort to beneficially participate in the intestinal microbiome-intestinal epithelia-innate-cell mediated immunity axes and cell mediated cellular immunity with vaccines aimed at preventing infectious diseases whilst conserving immunological tolerance. The strength of evidence for the positive effect of probiotic administration on acquired immune responses has come from various studies with viral and bacterial vaccines. We posit that the introduction early of probiotics may provide significant beneficial immune outcomes in neonates prior to commencing a vaccination schedule or in elderly adults prior to the administration of vaccinations against influenza viruses.

Keywords: immunological tolerance; infections; probiotics; vaccines.

Figure 1

Vaccine, epithelial barrier function and intestinal homeostasis. Intestinal immunological homeostasis is maintained by a complex interplay of the intestinal epithelial and localised immune cells. Antigen presenting macrophages/dendritic cells in the mucosa and associated lymphoid tissue, Peyer’s patches, mesenteric lymph nodes and lymphoid follicles co-ordinate immunological responses to maintain local homeostasis. Intestinal homeostasis supports the vaccine-induced production of antigen-specific antibodies via the presentation of vaccine antigen by migrating dendritic cells to B cells in the mucosa associated lymphoid tissue. Vaccine antigens also stimulate naïve CD4⁺ and CD8⁺ T cells to differentiate into cytotoxic T cells and to release antimicrobial cytokines. This figure was constructed and adapted from relevant published works [18,19,20].

Figure 2

Intestinal microbiome dysbiosis compromises the effectiveness of vaccine antigens secondary to systemic consequences of a chronic inflammation of the intestinal tract. In chronic intestinal inflammatory states, Tregs can suppress immune responses against antigens and this may limit the efficacy of vaccines when vulnerability signals are not sufficient to elicit vaccine-induced immunity via production of vaccine antigen-specific antibodies. A plausible posit is that probiotics can improve vaccine responses by encouraging the intestinal microbiome to restore eubiosis that restores intestinal immunological homeostasis. This figure was constructed and adapted from relevant published works [18,19,20,45,46,47,48].