In the pursuit of improved human health, prebiotics have grown exceedingly important. These non-digestible substances have the extraordinary ability to alter the gut microbiota, which has a significant impact on a number of facets of human health. Their significance stems from the multifaceted mechanisms through which they operate, and their roles extend from immunomodulation to disease management.
Through the process of rebiosis, or the growth of beneficial bacteria, prebiotics have the ability to affect the gut microbiota. They are able to counteract both pro- and anti-inflammatory reactions. Their capacity to stimulate different immune-related pathways is what causes these effects. For example, prebiotics can secrete regulating interleukin-10 (IL-10) and proinflammatory cytokines by activating the NF-κB pathway through Toll-like receptor 4 (TLR-4). Additionally, they have the ability to inhibit the proinflammatory response by activating the peroxisome proliferator-activated receptor-γ pathway. Furthermore, the prebiotic fermentation process yields short-chain fatty acids (SCFAs), which activate pathways such as NOD-like receptors and the inflammasome. This results in the release of antimicrobial peptides (AMPs), transforming growth factor-β, and anti-inflammatory IL-10.
Prebiotics have a unique ability to influence the host’s immune response both directly and indirectly. The innate immune system, the body’s first line of defense, is impacted by them in different ways. This system includes physical barriers like mucosal membranes as well as immune cells like neutrophils, macrophages, dendritic cells, lymphocytes, and natural killer (NK) cells. Prebiotics have the ability to directly activate immunological and gut-associated epithelial cells, causing either an anti- or pro-inflammatory reaction. Pattern recognition receptors (PRRs), which are found on cell surfaces and are capable of detecting exterior threats, are what trigger these reactions. Then, other transcription factors and signaling pathways, like NF-κB and activator protein 1 (AP-1), activate the genes that code for chemokines and cytokines, controlling inflammation.
Further, by producing SCFAs, prebiotics can indirectly affect the immunological response. When these SCFAs attach to G-protein-coupled receptors (GPCRs), signal transducer and activator of transcription (STAT), mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK) are activated. The synthesis of antimicrobial peptides and anti-inflammatory cytokines including TGF-β and IL-10 is triggered by this activation.
Maintaining Gut Barrier Function
The intestinal barrier, consisting of a monolayer of epithelial cells, serves as a selectively permeable defense against microbes, toxins, and antigens. Desmosomes, adhesion junctions, and tight junctions are examples of complex protein networks that are essential to maintaining the integrity of this barrier. If this barrier is compromised, it can lead to long-term inflammation and heightened intestinal permeability, which can make it possible for dangerous compounds like lipopolysaccharides (LPS) to enter the bloodstream.
It has been discovered that prebiotics have a beneficial effect on the intestinal barrier’s functionality. They improve tight junction assembly, which lowers permeability and inhibits the passage of cytokines and LPS. Prebiotics can sometimes trigger the release of peptides similar to glucagon, which improves diseases like type 1 diabetes and obesity, where the gut barrier has been compromised.
Effects of Microbiota on Immune Cells
Prebiotics and SCFAs have a significant impact on gut-dwelling immune cells in addition to epithelial cells. Regulatory T cells (Tregs), neutrophils, macrophages, natural killer (NK) cells, and dendritic cells (DCs) represent a few of these cells.
By exposing other immune cells to antigens, DCs are essential for controlling immunological responses. Prebiotics and SCFAs affect DC maturation, influencing the development of particular immune responses such as Th1, Th2, Th17, or Treg phenotypes. They also increase cytokine release.
Macrophages play a crucial role in preserving the integrity of the intestinal epithelium by being positioned strategically beneath it. Through epigenetic alterations and the suppression of proinflammatory mediators, SCFAs are essential in controlling macrophage polarization and augmenting anti-inflammatory responses. This lowers inflammation and promotes intestinal tolerance.
The regulation of inflammation and immunological tolerance depend on tregs. Prebiotics have been connected to elevated Treg activity, which improves immunity homeostasis and mitigates allergic reactions. This is mediated by both the suppression of histone deacetylase (HDAC) and the engagement of GPCRs by SCFAs.
Prebiotics also affect natural killer cells (NK cells), along with SCFAs can increase their cytotoxicity, improving their resistance to infections and cancer.
Neutrophils, a type of white blood cell, participate in inflammatory responses. SCFAs have been shown to modulate neutrophil function, inhibiting their proinflammatory activities and promoting the resolution of inflammation.
Conclusion
Prebiotics, these remarkable non-digestible compounds, offer a fascinating avenue for immune modulation. Their intricate interaction with the gut microbiota and the host’s immune system goes far beyond their role in gut health. The ability of prebiotics to influence immune cells and gut epithelial cells independently of the gut microbiota is a captivating area of research, shedding light on both pro-inflammatory and anti-inflammatory responses.
As our understanding of prebiotics’ mechanisms deepens, it becomes increasingly evident that these dietary components hold great potential for therapeutic applications in various conditions, particularly those involving immune dysregulation. The concept of prebiotics as a tool to promote immune balance and overall health is an exciting prospect that continues to unfold in the field of scientific inquiry. Prebiotics have the potential to serve as allies in our pursuit of well-being, and further research promises to uncover the full extent of their immunomodulatory powers.
