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.

Probiotics and prebiotics in intestinal health and disease: from biology to the clinic

“…probiotics have been shown to increase phagocytosis or natural killer cell activity and interact directly with dendritic cells (reviewed in 36 ) Some also demonstrate the ability to upregulate antibody secretion translating into improved defences against pathogens and augmenting vaccine responses. [37][38][39] Probiotic strains can increase levels of anti-inflammatory cytokines such as tumour necrosis factor with implications for abating colon cancer and colitis. 10,36 As discussed later, cell-surface architecture, such as fimbriae, capsule and surface structures expressed by certain probiotics is a mechanistic driver for several of these activities.…”

The microbiome and immune memory formation

“…Microbiome modification through the use of probiotics or prebiotics is classically used to induce immunomodulatory effects, which usually is not the desired effect to increase vaccine efficacy . However, in contrast to immunomodulation, pro‐ and prebiotics might also be able to provide an adjuvant effect that could increase vaccine efficacy . While some studies report significant increases in vaccine efficacy, the majority of studies only show modest or no effects.…”

“…56 However, in contrast to immunomodulation, pro-and prebiotics might also be able to provide an adjuvant effect that could increase vaccine efficacy. 57,58 While some studies report significant increases in vaccine efficacy, the majority of studies only show modest or no effects. Interpretation of these studies is often difficult because the experimental conditions differ significantly between studies.…”

Immunological Tolerance and Function: Associations Between Intestinal Bacteria, Probiotics, Prebiotics, and Phages

“…The human microbiome project ( 14 ) has redefined the role of bacteria that live on and within humans especially in the intestinal tract, from one that was considered to be a site of toxic waste and pathogenic bacteria to a site with important immunological activity ( 15 ). Recently, reviews have described how the role of probiotics enhancing immunological functions in the intestines to restore local and extra-intestinal mucosal and innate immunity equilibrium have gained significant support ( 16 , 17 ).…”