The immunomodulatory properties of probiotic microorganisms beyond their viability (ghost probiotics: proposal of paraprobiotic concept)

Abstract

The probiotic approach represents a potentially effective and mild alternative strategy for the prevention and treatment of either inflammatory or allergic diseases. Several studies have shown that different bacterial strains can exert their probiotic abilities by influencing the host's immune system, thereby modulating immune responses. However, the emerging concern regarding safety problems arising from the extensive use of live microbial cells is enhancing the interest in non-viable microorganisms or microbial cell extracts, as they could eliminate shelf-life problems and reduce the risks of microbial translocation and infection. The purpose of this review is to provide an overview of the scientific literature concerning studies in which dead microbial cells or crude microbial cell fractions have been used as health-promoting agents. Particular attention will be given to the modulation of host immune responses. Possible mechanisms determining the effect on the immune system will also be discussed. Finally, in the light of the FAO/WHO definition of probiotics, indicating that the word 'probiotic' should be restricted to products that contain live microorganisms, and considering the scientific evidence indicating that inactivated microbes can positively affect human health, we propose the new term 'paraprobiotic' to indicate the use of inactivated microbial cells or cell fractions to confer a health benefit to the consumer.

Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

“…31 We were not able to confirm these findings using mouse BM-DCs, and we did not observe any synergistic effects on cytokine production. This discrepancy may be explained by the different manners of bacterial inactivation (heating vs. formalin inactivation) 55 and also by the different donor species and cell types used.…”

S-Layer Protein Mediates the Stimulatory Effect of Lactobacillus helveticus MIMLh5 on Innate Immunity

“…In fact, dead or inactivated bacterial cells or even their single molecular components might also be effective in exerting beneficial immunostimulating properties, thus permitting the development of safer therapies for the treatment of specific diseases. This approach has recently been defined as paraprobiotic intervention (10).…”

“…The cross talk between host and intestinal/probiotic bacteria principally relies on the capacity of host cells to recognize specific bacterial components or products, thus giving rise to responses that most frequently involve the mucosa-associated lymphoid tissue (MALT) and, therefore, the immune system (9,10). Specifically, cell surface components of commensal or food/ probiotic bacteria, known as microbe-associated molecular patterns (MAMPs), can be identified by pattern recognition receptors (PRRs) on cells constituting the innate immune system, resulting in the activation of immune responses.…”

Probiotics for Human and Poultry Use in the Control of Gastrointestinal Disease: A Review of Real-World Experiences

“…Numerous researchers have reported the ability of live bacterial cultures to also reduce colonization of opportunistic microorganisms in the gastrointestinal tract [8,[29][30][31]. Balanced gastrointestinal microflora and immune-stimulation or regulation of cell mediated or humoral immunity are major functional effects attributed to the consumption of probiotics [18,26,[32][33][34][35][36]. However, several animal and human studies have provided unequivocal evidence that specific strains of probiotics are able to stimulate multiple aspects of innate immunity [3,8,20,[37][38][39][40].…”