Approaches to stimulate mucosal immunity in the intestinal tract of chickens

Optimal gut health is of vital importance to the performance of poultry and involves a number of physiological, microbiological, and physical functions that work together to maintain intestinal homeostasis and to withstand environmental and infectious stresses.

The mucosal immune system is responsible for interfacing with the outside world, specifically responding to external threats, of which pathogenic microbes represent a primary challenge. Modulating mucosal immunity should enhance the comprehensive immune functions, promote the resistance against various pathogenic invasions, and prevent intestinal damage or injuries. The gut microbiota has been implicated in the regulation of multiple intestinal functions including maintenance of barrier function and the induction, development, and modulation of immune responses. Thus, the mucosal immune system uses diverse mechanisms that protects the host from overt pathogens while also monitoring, nurturing, and exploiting the microbiota. Immune protection against infection is most efficient when localized at the sites of entry of the infectious agent. Since most infections occur at mucosal surfaces, improving mucosal vaccination is an active research goal in birds. However, the scientific challenges in this area are still diverse because oral administration of proteins induces tolerance, and not immune activation.

Alternatively, there has been extensive research into developing and evaluating contemporary immune modulators in poultry including: prebiotics/probiotics/direct fed microbials, phytochemicals, nutraceuticals, antimicrobial peptides (host defense peptides), essential oils, butyrate and organic acids, feed enzymes, and egg yolk antibodies. Unfortunately, classical therapies based on the consumption of live probiotic bacteria, or their enrichment by prebiotics, exhibit limited efficacy.

However, novel strategies are being developed for new microbiota-based and nanoparticle vaccine adjuvants and delivery systems as well as the development of DNA vaccines to improve the immunogenicity of antigens and induce a stronger immune response. Further, novel therapeutic approaches have been suggested based on metabolites secreted, modulated or degraded by the microbiome which may be able to provide therapeutic efficacy while overcoming caveats of current microbiome-targeting therapies, such as colonization resistance and inter-individual variation in microbial composition.

Additionally, direct stimulation of the innate immune response has shown great potential for protection against enteric pathogens, regardless of whether they are viral, bacterial, or protozoal in nature. Lastly, during infections of the gut, most pathogens are able to subvert host cell regulatory signaling pathways and re-program the metabolic pathways of many immune cells to a more immunosuppressive phenotype. Targeting these pathways to reverse this reprogramming has the potential to promote more pro-inflammatory responses and improve bacterial clearance.

Presented at the 7th International Conference on Poultry Intestinal Health, Cartagena, Colombia, 2022. For information on the next edition, click here.