Impact of prebiotics on immune response: from the bench to the clinic

Immunol Cell Biol. 2021 Mar;99(3):255-273. doi: 10.1111/imcb.12409. Epub 2020 Nov 2.


Several preclinical and clinical studies have shown the immunomodulatory role exerted by prebiotics in regulating the immune response. In this review, we describe the mechanistic and clinical studies that decipher the cell signaling pathways implicated in the process. Prebiotic fibers are conventionally known to serve as substrate for probiotic commensal bacteria that release of short-chain fatty acids in the intestinal tract along with several other metabolites. Subsequently, they then act on the local as well as the systemic immune cells and the gut-associated epithelial cells, primarily through G-protein-coupled receptor-mediated pathways. However, other pathways including histone deacetylase inhibition and inflammasome pathway have also been implicated in regulating the immunomodulatory effect. The prebiotics can also induce a microbiota-independent effect by directly acting on the gut-associated epithelial and innate immune cells through the Toll-like receptors. The cumulative effect results in the maintenance of the epithelial barrier integrity and modulation of innate immunity through secretion of pro- and anti-inflammatory cytokines, switches in macrophage polarization and function, neutrophil recruitment and migration, dendritic cell and regulatory T-cell differentiation. Extending these in vitro and ex vivo observations, some prebiotics have been well investigated, with successful human and animal trials demonstrating the association between gut microbes and immunity biomarkers leading to improvement in health endpoints across populations. This review discusses scientific insights into the association between prebiotics, innate immunity and gut microbiome from in vitro to human oral intervention.

Keywords: T cells; dendritic cells; immunomodulation; macrophage; oligosaccharide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gastrointestinal Microbiome*
  • Humans
  • Immunity, Innate
  • Microbiota*
  • Prebiotics
  • Probiotics*


  • Prebiotics