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Thoda, C.; Touraki, M. Immunomodulatory Properties of Probiotics. Encyclopedia. Available online: https://encyclopedia.pub/entry/43463 (accessed on 16 January 2025).
Thoda C, Touraki M. Immunomodulatory Properties of Probiotics. Encyclopedia. Available at: https://encyclopedia.pub/entry/43463. Accessed January 16, 2025.
Thoda, Christina, Maria Touraki. "Immunomodulatory Properties of Probiotics" Encyclopedia, https://encyclopedia.pub/entry/43463 (accessed January 16, 2025).
Thoda, C., & Touraki, M. (2023, April 25). Immunomodulatory Properties of Probiotics. In Encyclopedia. https://encyclopedia.pub/entry/43463
Thoda, Christina and Maria Touraki. "Immunomodulatory Properties of Probiotics." Encyclopedia. Web. 25 April, 2023.
Immunomodulatory Properties of Probiotics
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This entry is adapted from the peer-reviewed paper 10.3390/app13084726

The immune system plays a crucial role in orchestrating cellular and molecular key mediators, thus establishing a powerful defense barrier against infectious pathogens. Gut microbiota represent a complex community of numerous microorganisms that live in the mammalian gastrointestinal (GI) tract, which regulate the innate and adaptive immune responses contributing to the maintenance of gut homeostasis. The impairment in the crosstalk between intestinal immunity and gut microbiota may result in detrimental health issues. In this context, probiotics and their bioactive compounds, display distinct immunomodulatory properties through which they suppress inflammation and enhance the restoration of microbial diversity in disease. 

probiotics immunity immunomodulatory properties gut microbiota

1. Gut Microbiota and Immunity Crosstalk in Health and Disease

The gut microbiota, a group of microorganisms strictly compartmentalized to the intestinal lumen of the mammalian gastrointestinal (GI) tract [1],  involves more than 1000 bacterial species [2] which contribute to the maintenance of host health. A balanced gut microbiota protects against harmful opportunistic pathogens, hence it is directly associated with the establishment of gut homeostasis [3]. Gut microbiota participates in  various gut functions, including degradation of unmetabolized dietary components, production of essential nutrients, and secretion of bioactive compounds, such as SCFAs and bacteriocins, which present anti-inflammatory and immunomodulatory properties  [4] [5]. Gut microbiota imbalance, namely gut dysbiosis, is implicated in the development of acute or chronic inflammation and oxidative stress, provoking grievous health disorders [6]. Changes in the composition and diversity of the gut microbiota are associated with increased susceptibility to non-communicable diseases, such as metabolic disorders including obesity or type 2 diabetes [7], cardiovascular and neurodegenerative diseases [8], inflammatory bowel disease (IBD) or colorectal cancer (CRC) [1].
The connection between diseases and disrupted gut microbiota composition has been documented [8][9]. However, whether gut dysbiosis is the cause or consequence for the development of detrimental health issues remains ambiguous[10]. Resilience, defined as the ability of an ecosystem to return to its original state after perturbation caused by drug administration, pathogens invasion, and unhealthy lifestyle habits, constitutes the preponderant factor for a healthy gut microbiota [11]. In the gut microenvironment increased complexity and diversity of microbial communities has been associated with resilient microbiota  [12]. Although the determination of a healthy gut microbiota could significantly contribute to personalized medicine approaches, it is hindered by the lack of evidence regarding the microbiome diversity among individuals,  rendering the need for further research imperative [13].
Considering the fact that the majority of immune cells reside in the gut [12], the achievement of balance between inflammation and immune tolerance, holds the the prerequisite of gut microbiota interaction with the intestinal immune system [9]. The intestinal immune system comprises four main compartments: the gut-associated lymphoid tissue (GALT), the mesenteric lymph nodes (MLN), the lamina propria (LP), and the epithelial tissue [14]. GALT consists mostly of the Peyer’s patches,  the immune sensors of the intestine, and undertakes the role of eliminating  pathogens in the intestinal lumen of mammals [15]. Peyer’s patches, which are covered by the follicle-associated epithelium (FAE), contribute to the generation of immunoglobulin (Ig)- producing B cells [16]. In addition to the intestinal epithelial cells (IECs), the FAE includes two distinct types of specialized epithelial cells the microfold (M) cells, which transfer various mucosal antigens to the LP, and goblet cells, which are involved in the secretion of mucus [4]. The FAE serves as an effective barrier between host immune cells residing in the LP and bacteria, either commensal or pathogenic [4], which may be disrupted in case of gut dysbiosis [12]. Impairment in immune system–gut microbiota crosstalk may result in serious repercussions, such as deviant immune responses, systemic distribution of commensal microbes, and vulnerability to pathogenic infiltration [17].

2. Immunomodulatory Properties of Probiotics

Probiotics are non-pathogenic distinct microorganisms, which provide health benefits when administered in adequate amounts to the host [18], contributing to the maintenance of gut microbiota homeostasis [19]. They are considered to be a valuable option for the restoration of gut microbial diversity [19] and the treatment of infections caused by antibiotic resistant bacteria or invading viruses [6][15]. Probiotics produce a great variety of substances, which exhibit growth-inhibitory action against several pathogens and present a distinct effect on the microenvironment abiotic factors. The metabolic products secreted by probiotic bacteria, also known as postbiotics include vitamins, organic acids, SCFAs, neurotransmitters, flavonoids, amino acids, enzymes, bacteriocins, exopolysaccharides, cell wall fragments, teichoic acids, and biosurfactants [6].
The effects of probiotic bacteria on immunity are exerted through epithelial colonization with simultaneous induction of mucin secretion [19], competitive exclusion of pathogens by preventing their adherence on the intestinal epithelial surface [15], inhibition of pathogens’ proliferation through competition for essential nutrients [16][19], and production of several bioactive compounds [6]. The immunomodulatory properties of probiotics are mostly attributed to the release of cytokines and chemokines from immune cells [14], the activation of TLRs [16][20], or the inhibition of the nuclear factor-κB (NF-κB) pathway [21][22]. Probiotics are involved in the regulation of the JAK/STAT and the mitogen-activated protein kinase (MAPK) signaling pathways via the secretion of cytokines and antimicrobial peptides (AMPs), promoting the mucosal and systemic immune response [21][23]. Moreover, probiotic cellular fragments or surface molecules trigger the phagocytic capacity of macrophages and dendritic cells (DCs) [24][25][26] and enhance the cytotoxic activity of NK cells [27][28] and CD8+ T cells [29]. Probiotics induce the maturation and differentiation of adaptive immune cells through modulation of innate immune cells [30][31]. Following their adherence to the IECs, probiotics induce the secretion of cytokines resulting in the activation of Tregs, key mediators in maintaining gut homeostasis [12][16][32]. The increased production of the anti-inflammatory cytokine interleukin (IL)-10 by Tregs to the detriment of pro-inflammatory cytokines in the colonic mucosa may suppress inflammatory responses [12] and stimulate immune tolerance to commensal microbes [16][32]. Furthermore, the induction of Tregs promotes the immunoglobulin class switching by mature B cells, in the Peyer’s patches, towards the secretory IgA [33], which prevents the interaction of pathogens with epithelial receptors and preserves the integrity of the mucosal barrier [34][35]. Regarding T cell subtypes, probiotics promote a shift from Th2 to Th1 cells, in order to control autoimmune disorders [12][15]. 

The contribution of probiotics in the maintenance of a healthy gut microbiota and a balanced interaction between commensal bacteria and immune cells is noteworthy. However, despite their accredited beneficial effects on human health, it has been reported that administration of probiotics to eliminate treatment-related side effects in adult cancer patients leads to the development of undesired health issues including bacteremia, endocarditis, sepsis, and pneumonia [36]. Several factors could be accounted for the initiation of inflammatory responses upon probiotic treatment, such as gut microbiota variability between individuals, probiotic strain-specific function, and bacterial translocation to remote tissues or into the bloodstream [6]. Therefore, the evaluation of the risk-benefit ratio prior to probiotic administration to immunocompromised patients is of utmost importance. Additionally, clarification of the exact molecular mechanisms of probiotic action, selection of the appropriate bacterial strain for targeted therapy, and determination of the most efficient dose remain obligatory [36]. 

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Subjects: Biotechnology & Applied Microbiology
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