The role of probiotics in promoting systemic immune tolerance in systemic lupus erythematosus

The immune system is an intricate net of innate and adaptive components that can adapt and respond to different antigens [1]. Autoimmune diseases happen once the immune system loses tolerance and attacks auto-antigens in either cells or organs [2]. Immune tolerance is performed through central tolerance(mainly clonal deletion( and peripheral tolerance mechanisms(activation-induced cell death (AICD) and anergy) [3]. About 5% of the world’s people are affected by autoimmune disorders [4]. SLE is a long-lasting autoimmune disorder considered via the construction of autoantibodies and immune complexes [5, 6].

SLE is a complex progressive inflammatory autoimmune disease, in which various pro-inflammatory immune cells are activated. Chronic inflammation and hyperactive immune responses in SLE patients play a determinant role in the pathogenesis of the disease [7]. The prevalence of SLE varies widely between regions, with the current global prevalence estimated to be between 50 and 241 per 100,000 adults [8, 9]. Having lupus can make everyday life challenging. When lupus is active, symptoms like joint stiffness, pain, fatigue, confusion, or depression can make simple tasks difficult — and sometimes impossible [10]. In most cases, lupus is not lethal. In fact, 80–90% of people who have this autoimmune disease will likely live a normal life span [11]. To complement the management of SLE along with current treatments, nutritional intervention may offer a hopeful option. A diversity of dietary components such as vitamin D, omega-3 fish oils, curcumin, Glycaemic index (GI), and sodium have been reported to play a role in SLE management, as described by improvements in immunological function and bone mass density [12, 13]. However, the way nutritional interventions and specific dietary patterns modulate immune functions in SLE and whether they can improve disease activity remains unclear. SLE is characterized by multiple system and organ involvement, recurrent relapses and remissions, and the expansion of a huge reservoir of autoantibodies to double-stranded (ds) DNA [5, 14, 15]. The pathogenesis of SLE involves both non-specific and specific immunity, and its etiology is not fully unstated [16].

The pathogenesis of SLE includes a complex interaction between the exposome (environmental influence) and genome to produce an epigenetic alteration that alters the expression of specific genes that contribute to disease development [17, 18].

SLE exhibits a broad spectrum of presentations ranging from mild symptoms to severe, life-threatening conditions (Musculoskeletal, Central and peripheral nervous system, Gastrointestinal, Hematological, Pulmonary, Cardiovascular and Renal complication). Environmental factors, for example, cigarette smoking, UV light, and different infections may contribute to lupus [19‐21]. Genome-wide association surveys (GWAS) have recognized approximately 180 lupus vulnerability positions in the human genome, the greatest of which are associated with three biological procedures: lymphocyte signaling, type 1 interferon (IFN), and toll-like receptor signaling making, and apoptotic cell processing [22, 23]. The identified 330 risk loci represent a host of human biological processes and many potentially and possibly environmental processes involved in SLE pathogenesis [24].

SLE is characterized by the formation of autoantibodies, accumulation of self-reactive and inflammatory T cells, and nonstandard manufacture of cytokines with inflammatory cells and pro-inflammatory character [25, 26]. SLE is measured to be a predominantly B-cell-related disorder [27, 28]. An amount of T cell subgroups by immunoregulatory actions have been defined, and their role in defined autoimmune disorder models has been demonstrated [27, 29]. Regulatory T cells (Tregs) show a vital character in preserving tolerance and equilibrium in the immune system, and their depletion and dysfunction are related to the initiation and growth of autoimmune disease [30, 31]. Surveys have shown that boosting Treg cells can suppress unusual responses of functional T cells, which can effectively diminish autoimmune and inflammatory responses [32, 33]. Studies have exposed those disturbances in the number and function of CD4 + T helper cell subgroups, for example, Th17, Th2, Th1, and T follicular helper cells, occur in SLE [27, 34, 35]. In addition, an amplified number and function of Th17 cells have been revealed to perform an important character as the primary trigger of autoimmune responses in SLE [36, 37]. IL-17, the major moderator of Th17 cells, can influence the creation of proinflammatory cytokines and chemokines(IL-8, monocyte chemoattractant protein-1, growth-related oncogene protein-α), and by raising the quantity of granulocyte-macrophage colony-stimulating factor, it increases the stimulation of neutrophils at sites of inflammation [38, 39].

Also, different studies have revealed abnormal pro/anti-inflammatory cytokine release or function in SLE, which may indicate the disparity between various immune cell subsets, which show a significant character in SLE pathogenesis. Anti-inflammatory cytokines, for example, TGF-β, and pro-inflammatory cytokines, such as IFN-γ, IL-23/IL-17, and IL-6, have been shown to be dramatically elevated at diverse stages of SLE progress [40, 41]. Numerous investigational and medical surveys have revealed that IL-6 in serum is meaningfully raised in SLE-affected areas, resulting in the expansion of plasma cells and Th17 and inhibiting the differentiation of Tregs [42‐44]. In addition, signal transducer and activator of transcription 4 (STAT4), interferon regulatory factor 5 (IRF5), IRF7, toll-like receptor 7 (TLR7), and TLR9 are complicated in the production of pro-inflammatory cytokines by monocytes/macrophages, and IFN-I making via DCs that stimulate and exacerbate limited and general inflammation in SLE [45, 46]. The immunoregulatory impacts of TGF-β contribute to the diversity of Treg cells via stimulating Foxp3 appearance and inhibiting cytotoxic, Th1, and Th2 responses by reducing IL-2 production [47, 48].

A potential strategy to alleviate the symptoms of SLE may be to restore cytokine balance and repair defective immune cells. The treatments aim to reduce the mechanism of inflammatory cytokine production, interfere with cell-to-cell signaling, and inhibit cellular proliferation [49]. The most commonly used methods to treat lupus contain the utilization of immunosuppressive drugs, hydroxychloroquine, glucocorticoids, and biologic agents. These have been shown to advance long-term patient results [50, 51]. However, it is significant to note that there are significant undesirable effects related to these treatments. Adverse effects, which can even result in various clinical outcomes in patients with SLE: Renal impairment, opportunistic infections, and ocular complications. It is important to recognize new interferences that are effective, for example, targeted medications, or methods to decrease the opposing effects of these disadvantages.

The gut microbiota shows a character in the expansion and balance of systemic and mucosal immune response to enhance tolerance to innocuous bacteria although providing an appropriate reply to pathogens [52]. Variations in the host microbiota have been recognized as a significant environmental factor in susceptibility to metabolic and immunological diseases, including malnutrition [53], obesity [54], autoimmune diseases [55, 56], and neurological diseases [57, 58]. Recent evidence proposes that alterations in the structure of the gut microbiota might have a character in the pathogenesis of SLE [52, 59] (Fig. 1).

Earlier surveys have revealed that gut microbiota dysbiosis is related to SLE pathogenesis through immune system inequity, damaged intestinal barrier purpose, molecular mimicry, sex hormones, and biofilms [56, 60]. Several surveys in humans and mice have established the impact of gut microbiota dysbiosis on the onset and progression of SLE [59, 61, 62]. The lasting use of probiotics is thought to deactivate gut microbiota dysbiosis, leading in fewer severe symptoms of SLE [63, 64]. Immunoregulatory probiotics have no significant side effects and are considered boosters for the progression of Treg, controlling inflammatory responses and inducing tolerance [65, 66]. This review proposes to offer an impression of the immunoregulatory impacts of probiotics that can induce tolerance and modulate cytokines that contribute to the symptoms of SLE.

The vertebrate skin surface and mucosa are occupied via a variety of microorganisms, including bacteria and fungal, constituting the commensal microbiota [67]. The gut microbiota performs a critical role in providing numerous vital procedures, including homeostasis, immune regulation, epithelial barrier maintenance, and metabolic functions [68, 69]. Therefore, any factor that disrupts the host-microbe balance may affect microbiota homeostasis, which has an important influence on the regulation of host immune functions [70, 71].

Probiotics are well-defined as viable microorganisms that exert numerous advantageous impacts on the host when ingested at a suitable concentration [72]. There have been extensive studies in both animal and human experiments to determine their potential to avoid or treat an extensive range of diseases, including infections, autoimmune diseases, and inflammation [52, 73]. A sole aspect of probiotics is their ability to reduce pro-inflammatory situations by improving tolerogenic mechanisms [74, 75]. As identified probiotic microorganisms, class of lactic acid bacteria (LAB), for example, Lactococcus, Streptococcus, Lactobacillus, and Enterococcus, as well as Bifidobacterium, have an extended history of safe usage [76, 77]. Ex vivo and in vitro surveys have revealed that certain Bifidobacterium and Lactobacillus strains can regulate the Th/Treg axis by persuading Treg production from innocent progenitors [49, 78, 79].

Lactobacillus can enhance non-specific cellular immunity by triggering macrophages and NK cells and liberating various cytokines. It can also enhance the immune system of the intestinal mucosa by increasing the quantity of IgA + cells [80]. Lactobacillus adhere to the gastrointestinal mucosa through interaction with TLRs [81], and proteinaceous surface layer components to stimulate the host immune response [82]. They can also increase the appearance of MUC1, 2, 3, and tight junction (TJ) proteins in colonic epithelial cells, increase butyrate levels, and modulate the microbiome [83, 84]. Lactobacilli can also produce cytoprotective mixtures, for example, short-chain fatty acids (SCFAs) [85, 86]. SFCAs can induce the creation of retinoic acid by epithelial cells [87]. This interaction with TGF-β promotes Treg diversity [88, 89] and prevents Th17 cell differentiation [90]. Tolerogenic probiotics have been shown to reduce inflammation and increase regulatory mediators by reducing Th1/Th17 cell numbers and IFN-γ/IL-17 levels while increasing Treg frequency and TGF-β levels [91, 92]. Lactobacillus supplementation reduces inflammatory cytokines, increases anti-inflammatory cytokines (such as IL-10), and increases the number of Tregs [91, 93]. Certain Lactobacillus species have been shown to prevent neutrophil extracellular trap development(such as Lactobacillus rhamnosus), improve antioxidant position( such as Lactobacillus helveticus), and increase adhesion molecule expression in the gut (such as Lactobacillus fermentum) [7].

The quantitative contributions of environmental factors, host genetics, and diet to shaping the gut microbiota remain basically unknown. Important relations among host genotypes and their gut microbiota composition have been described in both human and mouse studies [94]. dietary effects on the gut microbiota and health are often confounded by variation in host genotypes and environmental exposures. However, accumulating evidence has proposed that long-term diet is a primary driver of the gut microbiota. As an extreme instance, two co-evolution studies of mammals and their gut microbiota has found that both gut microbiota composition and functions are adapted to their diet [95, 96]. In another more current study, the convergently evolved structure of the gut microbiome in ant-eating mammals, despite their phylogenetic diversity, powerfully proposes that diet is the major force shaping their microbiota [97].

Diet is among the most easily controlled factors that can potentially manipulate the gut microbiota. Studying the flexibility of the microbiota and its outlines of change, during and after dietary intervention, could permit the design of effective nutrition therapy. Ley et al. have shown that the ratio of Bacteroidetes: Firmicutes increases in the gut microbiota of people consuming either a fat-restricted or a carbohydrate-restricted low-energy diet for a year and that people who lost more weight displayed larger variations in the ratios of these taxa [98].

As a broad range of evidence has demonstrated that some diets and nutrients have antioxidant, anti-inflammatory and immunomodulatory effects on immunoinflammatory diseases. Nutritional therapy including restrictions on carbohydrate and protein and the use of nutritional supplements (i.e., vitamins, minerals and polyphenols) is a promising way to control inflammatory responses in SLE [13, 99]. Nutritional supplements may exert potentially prophylactic effects with fewer or no side effects than those of the classic pharmacological therapies besides reducing co-morbidities and improving the quality of life of patients with SLE. Islam et al. study showed, Because dietary supplementation of various macronutrients and micronutrients has showed immunomodulatory effects counting maintenance of homeostasis and improvement of physical and mental well-being of patients with SLE, it is suggested that these patients consume a balanced diet [12]. A Western diet low in fiber, high in sugar and fat, and rich in processed foods can worsen SLE activity by changing the diversity of the gut microbiome and disrupting the intestinal barrier [100, 101]. The nutrient-gut microbiome association has a significant role in the pathology of SLE. Resistant starch (RS) diet from fibrous foods can be fermented by the gut microbiome into several types and amounts of short-chain fatty acids (SCFAs) and have a beneficial effect on SLE outcomes in lupus-prone mice models. Furthermore, polyphenols, particularly from apples and oranges, can increase beneficial microorganisms in SLE patients [102].

Several probiotic studies have recently been conducted in patients with SLE [63, 103]. Studies have described important reductions in species richness, variety, and Firmicutes/Bacteroidetes proportion compared to healthy groups, as well as variations in the metabolic character of the gut microbiota [104‐106]. It has been proved that commensal microorganisms by Treg inducible capacity can be considered suitable strains to modulate excessive inflammatory responses and restore immune homeostasis in SLE [103]. Inflammation can be downregulated by several means, including removal of cell debris and apoptotic cells, removal of oxidized lipids, and hindering the motivation of mitogen-activated protein kinase (MAPK) and other pro-inflammatory cytokines [107, 108].

Lactobacillus delbrueckii and Lactobacillus rhamnosus have been revealed to be useful in growing Tregs and reducing proinflammatory cytokines and the harshness of the disease in mice with SLE [91]. Matching to the previous study, short-chain fatty acids produced via bifidobacteria, lactobacilli, and symbiotic bacteria activate receptors (FFAR2, FFAR3) on enterocytes and prevent inflammatory responses via hindering the nuclear factor-κ-light chain enhancer of B-cell stimulation path [109]. SCFAs overwhelm histone deacetylases, simplify the accumulation of Tregs, and affect gut balance and motility [110]. They too, stimulate tolerogenic DCs that stimulate immature T CD4 + cells to convert into Tregs [88, 89]. Histamine formed via L. reuteri 6475 responds with the H2 receptor on macrophages and intestinal epithelial cells, reducing the production of pro-inflammatory cytokines, including TNF-α, IL-12, and MCP-1 [111, 112]. The tolerogenic impacts of lactobacilli are supported via several molecular mechanisms. The peptidoglycan-related muropeptide stated via L. salivarius Ls33 has been suggested to induce anti-inflammatory effects [113, 114]. Lipoteichoic acid D-alanylation reduces anti-inflammatory situations related to Lactobacillus acidophilus and Lactobacillus plantarum [115]. Studies have shown that the appearance of many secretory proteins, for example, p40 and p70, and low levels of histamine produced via L. rhamnosus strains have defensive immunological impacts, whereas increased levels of histamine made via certain L. saerimneri strains may stimulate a proinflammatory response in the gut [116‐118]. Atypical release or function of anti-inflammatory cytokines, containing IL-10 and TGF-β, and inflammatory cytokines, counting IFN-γ, IL-23/IL-17and IL-6, have been shown to play a dramatic character in different stages of SLE [40, 119, 120].

B. bifidum has been found to decrease the making of IFN-γ in NK and PBMC cells [121]. In addition, B. breve and L. rhamnosus GG were observed to reduce IL-23 and IL-17 manufacture in PBMCs co-cultured with human intestinal cells [122]. While there is information on the impact of L. casei Shirota probiotics on IL-6 combination in B cells, it is necessary to reduce IL-6 in PBMCs [123]. The study found that certain bacteria, including Bacteroides, Parabateroides, Bilophila, and Succinivibrio, were completely associated with IL-21, IL-2R, IL-35, IFN-γ, IL-10, IL-17, and TWEAK. Gemmiger and Dialister were harmfully associated with IL-35, IL-2R, and IL-17 [124]. Additionally, the plenty of Roseburia and Faecali bacterium was contrarywise associated with IL-6, while the plenty of Roseburia had an adverse association with IL-2. Finally, the plenty of Bacteroides had a confident connection with IL-2 [125]. L. casei strain NIZO B255 and L. reuteri strain ASM20016 have been found to interact with DC-SIGN, which primes DCs to express increased titers of IL-10 and suppress the propagation of effector T-cells [126]. In addition, B. breve Yakult strain and L. rhamnosus strain JB-1 have been initiated to induce IL-10 making by a diverse mechanism involving the nomination of TLR2 on CD103 + DCs [127, 128]. Stimulation of TLR2 pathways is identified to stimulate the fast production of IL-10, which finally overwhelms the Th1-related cytokine IL-12 [127, 129]. Studies have shown that B. longum and B. lactis can encourage the appearance of TGF-β in PBMCs. This is related to the oppressive valance of Treg cells [130, 131]. B. longum restored tolerance by inducing the differentiation of Treg cells, maintained via the anti-inflammatory cytokines TGF-β and IL-10 [132]. Bifidobacterium has also been reported to prevent extreme activation of CD4 + T cells, thus maintaining the equilibrium of Th1, Th17, and Treg cells in patients with SLE [103, 133]. In addition, supplementation with Bifidobacterium bifidum avoids TCD4 + hyperactivation in patients with SLE [134, 135]. Firmicutes bacteria are primary creators of butyrate, which acting a dominant character in the production and conservation of Treg cells in several tissues, particularly in the gut [136]. These bacteria prevent the trans differentiation of T cells into Th1 and Th17 effectors cells, ensuring a well-adjusted manufacture of both inflammatory and anti-inflammatory cytokines [134] (Fig. 2).

Lupus patients often experience heightened immune responses due to triggers in the gut. Probiotics may help by: Reducing Inflammatory Responses, Strengthening the Gut Lining, Supporting Immune Health [109, 137]. in particular, an anti-inflammatory plant-based diet that is high in fruits, vegetables, whole grains (such as wild rice, quinoa, or barley), beans, and nuts has been associated with better health [138, 139]. No overarching diet exists for people with lupus. However, lupus is a systemic disease, so maintaining good nutritional habits will help your body remain as healthy as possible. Generally, doctors recommend a diet composed of about 50% carbohydrates, 15% protein, and 30% fat. Studies have shown that the initiator of immune responses may be Lactobacillus stains, while Bifidobacterium strains induce anti-inflammatory and Treg cells [140]. Both experimental and clinical trials have revealed that selective strains of probiotics(B. bifidum, Ruminococcue obeum, Blautia coccoids and L. casei stain Shirota) can reduce [49].

Animal models have suggested that gut microbiota, comprising B. bifidum, Ruminococcus obeum, Lactobacillus, and Blautia coccoides, may be directly complicated in disease expansion, and certain gut microbiota have been related to autoimmune diseases [141, 142]. Animal models have proven to be suitable tools in the survey of SLE, and between these models, pristane-induced mice are a reliable animal model of SLE, as they develop numerous of the characteristics of human lupus, in any strain of normal mice, irrespective of their genomic contextual [143, 144].

Lactobacillus has diverse effects on different lupus mouse models representing various genetic or environmental situations. This suggests that probiotic supplementation for lupus treatment should be tailored to individual genetic and environmental factors. Certain strains of Lactobacillus species have been exposed to have beneficial immunomodulatory or tolerogenic effects on the immune system [145]. It has been shown that lactobacilli have an immunoregulatory effect in pristane-induced mice, lupus-prone Murphy-Roth Large (MLR)/Mp-Faslpr (lpr) mice, and NZB/W F1 mouse models by increasing Tregs and decreasing Th17 and Th1 cells [146, 147].

Administration of Lactobacillus supplements has been revealed to elevate Treg cells and decrease Th17 cells, thereby restoring the Th17/Treg equilibrium [148, 149]. In another study, the harshness of pristane-stimulated lupus in mice was ameliorated by the administration of L. delbrueckii and L. rhamnosus, which upregulated Treg cells and reduced anti-dsDNA, the Abundance of Th1 cells, Th17 and their major cytokines, including IL-17a and proinflammatory cytokines such as IL-6 [91, 92]. The study establishes that enteral management of L. reuteri or lactobacilli alone or in combination in MRL/LPR mice can shift the equilibrium of Treg-Th17 towards Treg cell dominance in kidneys, decrease endotoxemia, reduce amounts of dsDNA-reactive IgG, reduce urinary protein, and advance patient existence [7, 147] (Table 1).

In previous studies, oral using of L. reuteri (GMNL-89), L. paracasei (GMNL-32), or L. reuteri (GMNL-263) successfully reduced hepatic programmed cell death and several inflammatory pointers in lupus-prone mice, containing matrix metalloproteinase-9 (MMP-9) action, inducible nitric oxide synthase (iNOS) appearance and CRP appearance [150]. Furthermore, treatment with these probiotic strains reduced Treg expression and the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the liver due to embarrassment of NF-κB and MAPK pathway [150, 151]. In addition, a study displayed that a diet containing L. casei prolonged the lifetime of MRL/lpr mice and prevented the extension of B220 + T cells in the mesenteric lymph nodes and spleen [152]. Consumption of Lactobacillus resulted in an anti-inflammatory environment by decreasing IL-6 and raising IL-10 production in the gut of SLE mice [147]. Furthermore, supplementing with L. reuteri amplified the distinction of CD4 + CD25 + FoxP3 + T cells in MRL/lpr mice [153]. Another survey displayed that the direction of L. paracasei and L. reuteri to mice (NZB/W) with severe lupus resulted in an important rise in antioxidant activity and a decrease in cytokines, for example, TNF-α and IL-6. In addition, Tregs were restored [109, 153].

Another survey has revealed that oral direction of a combination of all five types (L. gasseri, L. rhamnosus, L. oris, L. johnsonii, and L. reuteri) to three-week-old female MRL/Mp mice had anti-inflammatory impacts and reduced renal lymphadenopathy and splenomegaly [147, 154]. L. plantarum is a lactic acid bacterium. It has regulatory impacts, containing an elevation in Treg and IL-10 [155]. Researchers have revealed that using L. plantarum, L. reuteri, or L. casei in mice has anti-inflammatory properties, including IL-10 production, anti-apoptotic effects, and modulatory effects involving Treg cells, and also prolongs the life of SLE mice [148, 156]. When 30, 10 or 5% of the SLE gut microbiota was substituted with equal amounts of a combination of two Clostridia strains (CI: Blautia coccoides DSM935 and Ruminococcus obeum DSM25238), or Bifidobacterium bifidum LMG13195 (Bb), Bb and CI meaningfully decreased TCD4 + hyperactivation and Th17/Th1 balance, respectively [103]. In addition, B. fragilis ATCC 25,285 was established to help restore Th17/Treg hemostasis and improve lupus activity in MRL/lpr mouse [157]. Certain strains of lactobacilli convert tryptophan into potent immunomodulating compounds that bind to the aryl hydrocarbon receptor (AhR). Stimulation of the AhR has been detected to control the methylation situation of the IL-17 and FoxP3 gene promoters [158, 159] (Fig. 3).

Several species of lactobacilli have been revealed to have useful effects on the host in SLE. Previous human surveys have demonstrated the immunomodulatory impacts of Lactobacillus species on T cells and their controlling impacts on immune and inflammatory responses [7, 160].

Several trials have described the immunoregulatory impacts of convinced probiotics, counting L. reuteri, L. casei, L. acidophilus, L. delbrueckii, L. rhamnosus, L. plantarum, B. breve, B. infantis, and B. longum, in patients with inflammatory and autoimmune diseases [161‐163]. One research investigated stool examples from uncured patients with SLE and found that their gut microbiota had an inflammatory and autoimmune outline in contrast to normal peoples [105]. Previous studies have shown that SLE patients in active form, have a lesser Firmicutes to Bacteroidetes proportion than normal persons [106]. The same study mentioned above found that synbiotics supplementation increased the Firmicutes to Bacteroidetes proportion and enhanced butyrate metabolism [164]. Butyrate has anti-inflammatory features by preventing the translocation of NF-kB to the nucleus, leading to reduced transcription of genes responsible for the manufacture of pro-inflammatory molecules [165](Table 2).

One study exhibited that the combination of L. delbrueckii and L. rhamnosus increased the appearance of the FoxP3 + cells in the culture of PBMCs from patients with SLE [166]. Several studies on autoimmune disorders have revealed that L. delbrueckii and L. rhamnosus can increase the amounts of repressive cytokines in PBMCs and T cells, while decreasing the manufacture of inflammatory molecules [122, 167, 168]. In vitro, lactobacilli, when cultured with undeveloped DCs from SLE patients in progressive stage, decrease the appearance of costimulatory molecules and increase the amount of IL-10 and IDO, proposing that they may enhance immune tolerance [169]. One study inspected the consequence of gut dysbiosis on the differentiation of Th1, Treg, and Th17 cells in SLE patients and healthy controls in vitro. The results showed a significant reduction in the Th17/Th1 balance and induction of Th17 differentiation [103]. Another study found that supplementation with Lactobacillus spp reduced IL-6 and amplified IL-10 manufacture in the gut, suggesting an anti-inflammatory effect [147]. Bifidobacterium may help maintain the stability of Th1/Th17/Treg via overwhelming extreme activation of TCD4 + cells in SLE patients [103, 170, 171], and supplementation with B. bifidum LMG13195 has been shown to prevent TCD4 + overactivation in SLE patients. However, Ruminococcus obeum DSM25238, Blautia coccoides DSM935, and Clostridia, meaningfully decreased the IL-17/IFN-γ (Th17/Th1) equilibrium, thereby recovering the Th1 prejudice [103].

The use of A. muciniphila and L. plantarum probiotics promoted an anti-inflammatory situation, which was attained via decreasing the appearance of the pro-inflammatory cytokines IL-17 and IL-6 while increasing the titers of the anti-inflammatory cytokine IL-10 in the circulation [172]. In conclusion, probiotics have anti-inflammatory characteristics and improve intestinal barrier function throughout the disease.

Probiotics in the gut play numerous physiological roles in the body, primarily metabolic and immunological functions. Also, probiotic have role in they have in metabolism: nutrient absorption, short-chain fatty acids. Gut microbiota dysbiosis can induce autoimmunity through possible mechanisms such as translocation and molecular mimicry, leading to immune cell and cytokine dysregulation and contributing to the advancement and progression of SLE. Studying the gut microbiota will provide a good opportunity to identify microbes involved in tolerance in systemic lupus patients. Probiotic use has been shown to be effective in producing anti-inflammatory or regulatory cytokines and anti-inflammatory metabolites that play a role in improving the clinical symptoms of SLE. By producing Treg cells and anti-inflammatory cytokines such as TGF-β and IL-10, probiotics are effective in improving SLE disease. Based on this documented evidence, the above probiotic strains could be proposed for additional clinical trials in SLE patients. Additional studies and clinical trials are essential to acquire a deeper understanding of the fundamental mechanisms accountable for the efficacy of probiotic regimens in SLE therapy.