Signaling pathways involved in the effect of probiotics on the immune system
Signaling pathways involved in the effect of probiotics on the immune system
Mohammad Amin Tokallou,1Seyed Alireza Esmaeili,2,*Mahmoud Mahmoudi,3Ehsan Rastgoo,4Abbas Sabouri,5
1. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2. Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3. Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 4. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 5. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Introduction: Probiotics are live microorganisms that, when consumed in adequate amounts, confer health benefits to the host. They play a pivotal role in maintaining gut health, supporting digestion, and modulating the immune system. Probiotics interact with the immune system in various ways, including balancing the immune response, strengthening the gut barrier, and stimulating the activation of beneficial immune cells.
Understanding the underlying signaling pathways involved in probiotic-mediated immune cell activation is crucial for several reasons. First, it allows for the development of targeted therapies that can harness the specific immunomodulatory properties of probiotics to treat various diseases. Second, knowledge of these signaling pathways enables the optimization of probiotic formulations, ensuring that they deliver maximum benefits to the host. Finally, studying probiotic-induced immune signaling provides valuable insights into the complex interactions between the gut microbiome and the immune system, contributing to a deeper understanding of human health and disease.
This article aims to delve into the intricate details of the signaling pathways involved in the immunomodulatory effects of probiotics.
Methods: The article used Google Scholar to discover recent research (2020-2024) examining the influence of probiotics on immune cells. The advanced search function was employed to pinpoint studies concentrating on the specific signaling pathways implicated in this process.
Results: Probiotics exert diverse effects on the immune system by influencing various cellular processes. They can alter receptor function, protein expression, and signaling pathways. Additionally, probiotics can regulate gene expression, inflammation, and the production of immune-related molecules. Key signaling pathways involved in probiotic-mediated immune modulation include MAPK, NF-κB, Akt/PI3K, and PPARγ. However, the specific effects of probiotics on these pathways and cytokine profiles can vary depending on the probiotic species. Probiotics have demonstrated anti-tumor properties through various mechanisms. For instance, Heptelidic acid from Aspergillus oryzae inhibits pancreatic cancer cell growth via P38 MAPK signaling. Bacillus coagulans MZY531 exhibits anti-apoptotic effects and reduces cancer cell survival by inhibiting AKT, mTORp-PI3K phosphorylation. Other probiotics, such as Lactobacillus casei BL23 and Clostridium butyricum, promote anti-tumor responses by increasing IL-2 production and activating the Wnt signaling pathway. Probiotics can also modulate inflammatory responses. Lactilactobacillus sakei WB2305 and Lactiplantibacillus plantarum WB2324 inhibit LPS-induced inflammation by targeting MAPK and NF-κB pathways. The capsular polysaccharide of Lacticaseibacillus paracasei 6235 can also modulate inflammation by altering MAPK and NF-κB protein expression. NF-κB, a key regulator of the immune system, is a common target of probiotic modulation. Probiotics can influence NF-κB activity by affecting TLR expression or p65 phosphorylation. Beyond NF-κB, probiotics can interact with other immune signaling pathways. Bacillus paralicheniformis alleviates ulcerative colitis by regulating the inflammasome through NLRP3. GABA-producing probiotics can inhibit the inflammasome pathway by targeting NLRP3. Additionally, Lactobacillus paracasei KW3110 suppresses multiple inflammasome complexes through an interleukin-10-dependent mechanism. Extracellular vesicles (EVs) derived from probiotics can also influence immune responses. For example, EVs from E. faecalis can induce an M1 macrophage phenotype by activating the NOD2/RIPK2 signaling pathway.
Conclusion: Probiotics have a broad range of effects on the immune system. They interact with cells in different ways, affecting things like receptor function, protein production, gene activity, and the creation of substances involved in immune responses. Key signaling pathways influenced by probiotics include MAPK, NF-κB, Akt/PI3K, and PPARγ. Although the specific effects can vary between different types of probiotics, they’ve been shown to help fight cancer, reduce inflammation, and regulate the immune system. Additionally, tiny particles called extracellular vesicles, released by probiotics, can also impact immune responses.