Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic joint inflammation. Existing therapeutic regimens, including disease-modifying anti-rheumatic drugs (DMARDs) and biologics, exhibit incomplete efficacy and pronounced limitations. RNA interference (RNAi) utilizing small interfering RNA (siRNA) facilitates the precise silencing of key pathological drivers in rheumatoid arthritis (RA), such as tumor necrosis factor-alpha (TNF-α), interleukins IL-1 and IL-6, as well as pivotal inflammatory pathways including NF-κB. This comprehensive systematic review meticulously analyzes 140 studies focusing on therapeutic siRNA for RA. The utilization of siRNA in RA involves the profound inhibition of macrophage and fibroblast-like synoviocyte (FLS) activation through the strategic targeting of TNF, RELA, and MAPK/JAK signaling pathways. In addition, siRNA diminishes inflammatory responses by suppressing critical inflammasome constituents like NLRP3 and fosters the reestablishment of immune equilibrium via downregulation of Th17 differentiation factors and augmentation of regulatory T cell (Treg) functions. It also directly reduces the aggressiveness of FLS by inhibiting pathological signaling components such as CCN1, KHDRBS1 and E2F2. Experimental studies in rodent models have demonstrated that targeted delivery of siRNA via nanoparticles against pathogenic mediators significantly suppresses paw inflammation and mitigates joint destruction. Although challenges such as stability, off-target effects, and efficient delivery remain, advancements in molecular modifications and nanoparticle technology offer promising solutions to these obstacles. In conclusion, unlike the traditional single-target DMARDs or biologics, multi-target RNA interference presents a highly precise mechanism to inhibit intracellular inflammatory cascade and joint damage progression in RA, offering a potential deterrent to disease advancement.

In recent years, the study of gut microbiota has gradually become a research hotspot in the field of medicine, as gut microbiota dysbiosis is closely related to various diseases. Thalassemia, as a hereditary hemoglobinopathy, has a complex pathophysiological mechanism, and traditional treatment methods show limited efficacy. With a deeper understanding of the gut microbiome, researchers have begun to focus on its role in the pathogenesis of thalassemia and its therapeutic effects. This article aims to review the role of gut microbiota in thalassemia and its potential therapeutic prospects, analyze the latest research findings, and explore the impact and mechanisms of gut microbiota on patients with thalassemia, with the goal of providing new ideas and directions for future research and clinical treatment of thalassemia.

The human body constitutes a living environment for trillions of microorganisms, which establish the microbiome and, the largest population among them, reside within the gastrointestinal tract, establishing the gut microbiota. The term "gut microbiota" refers to a set of many microorganisms [mainly bacteria], which live symbiotically within the human host. The term "microbiome" means the collective genomic content of these microorganisms. The number of bacterial cells within the gut microbiota exceeds the host's cells; collectively and their genes quantitatively surpass the host's genes. Immense scientific research into the nature and function of the gut microbiota is unraveling its roles in certain human health activities such as metabolic, physiology, and immune activities and also in pathologic states and diseases. Interestingly, the microbiota, a dynamic ecosystem, inhabits a particular environment such as the human mouth or gut. Human microbiota can evolve and even adapt to the host's unique features such as eating habits, genetic makeup, underlying diseases, and even personalized habits. In the past decade, biologists and bioinformaticians have concentrated their research effort on the potential roles of the gut microbiome in the development of human diseases, particularly immune-mediated diseases and colorectal cancer, and have initiated the assessment of the impact of the gut microbiome on the host genome. In the present chapter, we focus on the biological features of gut microbiota, its physiology as a biological factory, and its impacts on the host's health and disease status.

Gut microbiota regulates the immune system, the development and progression of autoimmune diseases (AIDs) and overall health. Recent studies have played a crucial part in understanding the specific role of different gut bacterial strains and their metabolites in different AIDs. Microbial signatures in AIDs are revealed by advanced sequencing and metabolomics studies. Microbes such as Faecalibacterium prausnitzii, Akkermansia muciniphila, Anaerostipes caccae, Bacteroides sp., Roseburia sp., Blautia sp., Blautia faecis, Clostridium lavalense, Christensenellaceae sp., Coprococcus sp., Firmicutes sp., Ruminococcaceae sp., Lachnospiraceae sp., Megamonas sp., Monoglobus sp., Streptococcus pneumoniae and Bifidobacterium sp. help maintain immune homeostasis; whereas, Prevotella copri, Ruminococcus gnavus, Lactobacillus salivarius, Enterococcus gallinarum, Elizabeth menigoseptica, Collinsella sp., Escherichia sp., Fusobacterium sp., Enterobacter ludwigii, Enterobacteriaceae sp., Proteobacteria, Porphyromonas gingivalis, Porphyromonas nigrescens, Dorea sp., and Clostridium sp. cause immuno-pathogenesis. A complex web of interactions is revealed by understanding the influence of gut microbiota on immune cells and various T cell subsets such as CD4+ T cells, CD8+ T cells, natural killer T cells, γδ T cells, etc. Certain AIDs, including rheumatoid arthritis, diabetes mellitus, atopic asthma, inflammatory bowel disease and non-alcoholic fatty liver disease exhibit a state of dysbiosis, characterized by alterations in microbial diversity and relative abundance of specific taxa. This review summarizes recent developments in understanding the role of certain microbiota composition in specific AIDs, and the factors affecting specific regulatory T cells through certain microbial metabolites and also focuses the potential application and therapeutic significance of gut microbiota-based interventions as novel adjunctive therapies for AIDs. Further research to determine the precise association of each gut bacterial strain in specific diseases is required.

Diagnostic markers for myasthenia gravis (MG) are limited; thus, innovative approaches are required for supportive diagnosis and personalized care. Gut microbes are associated with MG pathogenesis; however, few studies have adopted machine learning (ML) to identify the associations among MG, gut microbiota, and metabolites. In this study, we developed an explainable ML model to predict biomarkers for MG diagnosis. We enrolled 19 MG patients and 10 non-MG individuals. Stool samples were collected and microbiome assessment was performed using 16S rRNA sequencing. Untargeted metabolic profiling was conducted to identify fecal amplicon significant variants (ASVs) and metabolites. We developed an explainable ML model in which the top ASVs and metabolites are combined to identify the best predictive performance. This model uses the SHapley Additive exPlanations method to generate both global and personalized explanations. Fecal microbe-metabolite composition differed significantly between groups. The key bacterial families were Lachnospiraceae and Ruminococcaceae, and the top three features were Lachnospiraceae, inosine, and methylhistidine. An ML model trained with the top 1 % ASVs and top 15 % metabolites combined outperformed all other models. Personalized explanations revealed different patterns of microbe-metabolite contributions in patients with MG. The integration of the microbiota-metabolite features and the development of an explainable ML framework can accurately identify MG and provide personalized explanations, revealing the associations between gut microbiota, metabolites, and MG. An online calculator employing this algorithm was developed that provides a streamlined interface for MG diagnosis screening and conducting personalized evaluations.

Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC's effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.

We aimed to investigate the relationship between the peripheral lymphocyte subset frequency and thymectomy in patients with myasthenia gravis (MG).

The frequencies of regulatory B (Breg) and regulatory T (Treg) cells in peripheral blood samples obtained from 69 patients with MG and 10 healthy controls were analyzed using flow cytometry. Serum acetylcholine receptor antibodies (AchR-Ab) were measured. Patients with MG were subdivided into pre-thymectomy, post-thymectomy, and normal thymus control group.

The percentage of Breg cells was significantly decreased in both the pre-thymectomy (7.92 ± 1.30%) and post-thymectomy (8.14 ± 1.34%) groups compared to healthy controls (16.02 ± 2.78%) and reduced in the exacerbation and relapse phase compared to the stable maintenance stage. The proportion of cluster of differentiation (CD) 4 + CD25 + T cells and CD4 + CD25 + CD127low/- Treg cells in MG patients were not significantly different than healthy controls. AchR-Ab titers in aggravating or recurrence patients after thymectomy were significantly higher than that of the stable remission patients (11.13 ± 0.70 and 6.03 ± 0.85 nmol/L, respectively; p < 0.001).

The frequency of Breg cells may serve as a potential indicator of MG prognosis, while Treg cell frequency did not demonstrate the same prognostic ability. The concentration of AchR-Ab can be used as a dynamic monitoring index of disease severity in patients with MG.

Myasthenia gravis (MG) is an autoimmune disorder. Microvesicle-derived miRNAs have been implicated in autoimmune diseases. However, the role of microvesicle-derived miR-29a-3p in MG remains poorly understood. This study aimed to investigate the therapeutic effect and mechanism of miR-29a-3p derived from stem cell microvesicles (MVs) on experimental autoimmune myasthenia gravis (EAMG) rats.

EAMG was induced in rats by injection of the subunit of the rat nicotinic anti-acetylcholine receptor (AChR) R97-116 peptide.Besides the control group, EAMG rats were randomly allocated into the EAMG model group, MV group, MV-NC-agomir group, and MV- miR-29a-3p-agomir group.

Our results found that BMSCs-MV promoted miR-29a-3p expression in gastrocnemius of EAMG rats. Bone marrow mesenchymal stem cells (BMSCs) derived microvesicle miR-29a-3p improved the hanging ability and swimming time of EMGA rats and weakened the degree of muscle fiber atrophy. Furthermore, microvesicles from miR-29a-3p overexpressing BMSCs reduced the content of AchR-Ab in the serum of EAMG rats. BMSC-derived microvesicle miR-29a-3p further suppressed the expression of IFN-γ and enhanced the IL-4 and IL-10 in the serum of EAMG rats by restoring the Th17/Treg cells balance.

BMSCs-derived microvesicle miR-29a-3p improved the stability of rat myasthenia gravis by regulating Treg/Th17 cells. It may be an effective treatment for MG.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by a malfunction of the body's immune defense system.

The objective of the present investigation was to examine the expression and diagnostic significance of NRIR in SLE and to prove whether it is involved in the progression of SLE.

The study involved 110 participants, including 55 healthy individuals and 55 SLE patients. The expression levels of NRIR, miR-31-5p, and ICAM-1 were measured using qRT-PCR. The ROC curve was performed to assess the diagnostic significance of NRIR in SLE patients. Pearson correlation analysis was utilized to explore the relationship between NRIR and other indicators. Cytokines including IL-4, IL-6, and IL-21, along with IgG levels, were assessed using ELISA. The interaction between NRIR and miR-31-5p was validated using a dual-luciferase reporter assay.

Upregulated expression of NRIR was observed in individuals with SLE, serving a diagnostic function for SLE. Additionally, abnormal expression of NRIR impacted the viability of CD4+ T cells within SLE patients. NRIR could negatively modulate the expression of miR-31-5p.

LncRNA NRIR may be a potential biomarker for SLE and is likely involved in the progression of SLE.

Dihydroartemisinin (DHA), a derivative and active metabolite of artemisinin, possesses various immunomodulatory properties. However, its role in myasthenia gravis (MG) has not been clearly explored. Here, we investigated the role of DHA in experimental autoimmune myasthenia gravis (EAMG) and its potential mechanisms.

The AChR97-116 peptide-induced EAMG model was established in Lewis rats and treated with DHA. Flow cytometry was used to assess the release of Th cell subsets and Treg cells, and 16S rRNA gene amplicon sequence analysis was applied to explore the relationship between the changes in the intestinal flora after DHA treatment. In addition, network pharmacology and molecular docking were utilized to explore the potential mechanism of DHA against EAMG, which was further validated in the rat model by immunohistochemical and RT-qPCR for further validation.

In this study, we demonstrate that oral administration of DHA ameliorated clinical symptoms in rat models of EAMG, decreased the expression level of Th1 and Th17 cells, and increased the expression level of Treg cells. In addition, 16S rRNA gene amplicon sequence analysis showed that DHA restored gut microbiota dysbiosis in EAMG rats by decreasing Ruminococcus abundance and increasing the abundance of Clostridium, Bifidobacterium, and Allobaculum. Using network pharmacology, 103 potential targets of DHA related to MG were identified, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that PI3K-AKT signaling pathway was related to the treatment of DHA on EAMG. Meanwhile, molecular docking verified that DHA has good binding affinity to AKT1, CASP3, EGFR, and IGF1. Immunohistochemical staining showed that DHA treatment significantly inhibited the phosphorylated expression of AKT and PI3K in the spleen tissues of EAMG rats. In EAMG rats, RT-qPCR results also showed that DHA reduced the mRNA expression levels of PI3K and AKT1.

DHA ameliorated EAMG by inhibiting the PI3K-AKT signaling pathway, regulating CD4+ T cells and modulating gut microbiota, providing a novel therapeutic approach for the treatment of MG.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) that results from autoantibodies against nicotinic acetylcholine receptors (nAchRs) at NMJs. These autoantibodies are mainly originated from autoreactive B cells that bind and destroy nAchRs at NMJs preventing nerve impulses from activating the end-plates of skeletal muscle. Indeed, immune dysregulation plays a crucial role in the pathogenesis of MG. Autoreactive B cells are increased in MG due to the defect in the central and peripheral tolerance mechanisms. As well, autoreactive T cells are augmented in MG due to the diversion of regulatory T (Treg) cells or a defect in thymic anergy leading to T cell-mediated autoimmunity. Furthermore, macroautophagy/autophagy, which is a conserved cellular catabolic process, plays a critical role in autoimmune diseases by regulating antigen presentation, survival of immune cells and cytokine-mediated inflammation. Abnormal autophagic flux is associated with different autoimmune disorders. Autophagy regulates the connection between innate and adaptive immune responses by controlling the production of cytokines and survival of Tregs. As autophagy is involved in autoimmune disorders, it may play a major role in the pathogenesis of MG. Therefore, this mini-review demonstrates the potential role of autophagy and autophagy activators in MG.Abbreviations: Ach, acetylcholine; Breg, regulatory B; IgG, immunoglobulin G; MG, myasthenia gravis; NMJ, neuromuscular junction; ROS, reactive oxygen species; Treg, regulatory T; Ubl, ubiquitin-like.

The coexistence of Parkinson's disease (PD) and myasthenia gravis (MG) is rare. When similar symptoms of both diseases overlap, it is challenging to make a concomitant diagnosis of PD and MG. The present study describes the case of a patient with concomitant PD and MG. In addition, a systematic literature review was conducted by searching PubMed and Embase for reports on all patients with concomitant PD and MG, which were then grouped and compared according to different preexisting diseases. Finally, a total of 47 cases of concomitant PD and MG (35 men; 12 women), including the present case, were analyzed. The median age of the patients at first diagnosis was 66.59±9.91 years. The interval between the two diseases varied from 2 months to 22 years. Based on the sequential occurrence of these two diseases, the patients were categorized into three groups: The prePD-MG (30 cases), preMG-PD (12 cases), and coPD-MG (5 cases) groups. In the prePD-MG group, the onset age of MG was older and head drop was more common. In the preMG-PD group, the patients were more likely to have comorbid immune diseases.

Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by the production of autoantibodies against the postsynaptic membrane receptors present at the neuromuscular junction. This condition is characterized by fatigue and muscle weakness, including diplopia, ptosis, and systemic impairment. Emerging evidence suggests that in addition to immune dysregulation, the pathogenesis of MG may involve mitochondrial damage and ferroptosis. Mitochondria are the primary site of energy production, and the reactive oxygen species (ROS) generated due to mitochondrial dysfunction can induce ferroptosis. Nanomedicines have been extensively employed to treat various disorders due to their modifiability and good biocompatibility, but their application in MG management has been rather limited. Nevertheless, nanodrug delivery systems that carry immunomodulatory agents, anti-oxidants, or ferroptosis inhibitors could be effective for the treatment of MG. Therefore, this review focuses on various nanoplatforms aimed at attenuating immune dysregulation, restoring mitochondrial function, and inhibiting ferroptosis that could potentially serve as promising agents for targeted MG therapy.

Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components expressed at neuromuscular junctions, such as acetylcholine receptor (AChR). Interleukin-6 (IL-6) has been suggested to play a role in the pathogenesis of MG, and IL-6 receptor (IL-6R) antibody treatment may provide a novel therapeutic option. In this study, we investigated the effects of IL-6R antibody treatment in an experimental autoimmune MG (EAMG) mouse model. We demonstrated that IL-6R antibody treatment improved muscle weakness, reduced IgG deposition at neuromuscular junctions, and the levels of AChR autoantibodies in serum. In addition, follicular helper T cells and Th17, plasma cells in lymph nodes were lower in IL-6R antibody treated mice. Our findings suggest that IL-6R blockade may be a novel and effective therapeutic strategy for the treatment of MG.

Sepsis is a multi-organ dysfunction characterized by an unregulated host response to infection. It is associated with high morbidity, rapid disease progression, and high mortality. Current therapies mainly focus on symptomatic treatment, such as blood volume supplementation and antibiotic use, but their effectiveness is limited. Th17/Treg balance, based on its inflammatory property, plays a crucial role in determining the direction of the inflammatory response and the regression of organ damage in sepsis patients. This review provides a summary of the changes in T-helper (Th) 17 cell and regulatory T (Treg) cell differentiation and function during sepsis, the heterogeneity of Th17/Treg balance in the inflammatory response, and the relationship between Th17/Treg balance and organ damage. Th17/Treg balance exerts significant control over the bloom and wanes in host inflammatory response throughout sepsis.

Allergy and immunological disorders like autoimmune diseases are vastly prevalent worldwide. These conditions account for a substantial amount of personal and social burden. Such illnesses have lengthy, uncertain, and spotted courses with unpredictable exacerbations. A definite tendency for improving the overall quality of life of individuals suffering from such diseases is crucial to tackling these diseases, especially through diet or lifestyle modification. Further, interventions like microbiome-based therapeutics such as prebiotics or probiotics were explored. Changes in the microbial population were evident during the flare-up of autoimmune and allergic conditions. The realization that the human microbiome is a central player in immunological diseases is a hallmark of its potential usefulness in therapy for such illnesses. This review focuses on the intricate symphony in the orchestra of the human microbiome and the immune system. New therapeutic strategies involving probiotics appear to be the future of personalized medicine. Through this review, we explore the narrative of probiotics and reaffirm their use as therapeutic and preventive agents in immunological disorders.

To assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical improvement in patients with myasthenia gravis (MG).

28 anti-AchR positive MG patients treated with ofatumumab and 28 healthy controls (HCs) were included. Frequencies of cTfh and cTh17 cells were monitored by flow cytometry at baseline and 4, and 12 weeks after the initial dose ofatumumab. Serum cytokines associated with cTfh and cTh17, including IL-6, IL-21, and IL-17, were also analyzed.

The frequency of cTfh and cTh17 significantly increased in MG patients compared with HCs. Additionally, elevated levels of both T-cell subsets correlated with MG severity. During the follow-up, cTfh and cTh17 return to normal after BCDT. Furthermore, the decrease in cTfh and cTh17 was associated with MG scores improvement over time. Notably, cTfh- and cTh17-related cytokines, including IL-6, IL-21, and IL-17, exhibited a marked decrease following ofatumumab therapy.

Abnormal expansion of cTfh and cTh17 cells may be key features in the immunopathology of MG. Their levels returned to normal after BCDT, which was closely correlated with clinical amelioration. This result suggests that these two T-cell subsets may be targets for BCDT treatment of MG.

The changes in T regulatory cell (Treg) and T helper cell (Th) 17 ratios holds paramount importance in ensuring internal homeostasis and disease progression. Recently, novel subsets of Treg and Th17, namely IL-17-producing Treg and IL-10-producing Th17 have been identified. IL-17-producing Treg and IL-10-producing Th17 are widely considered as the intermediates during Treg/Th17 transformation. These "bi-functional" cells exhibit plasticity and have been demonstrated with important roles in multiple physiological functions and disease processes. Yin and Yang represent opposing aspects of phenomena according to the ancient Chinese philosophy "Yin-Yang" theory. Furthermore, Yin can transform into Yang, and vice versa, under specific conditions. This theory has been widely used to describe the contrasting functions of immune cells and molecules. Therefore, immune-activating populations (Th17, M1 macrophage, etc.) and immune overreaction (inflammation, autoimmunity) can be considered Yang, while immunosuppressive populations (Treg, M2 macrophage, etc.) and immunosuppression (tumor, immunodeficiency) can be considered Yin. However, another important connotation of "Yin-Yang" theory, the conversion between Yin and Yang, has been rarely documented in immune studies. The discovery of IL-17-producing Treg and IL-10-producing Th17 enriches the meaning of "Yin-Yang" theory and further promotes the relationship between ancient "Yin-Yang" theory and modern immunology. Besides, illustrating the functions of IL-17-producing Treg and IL-10-producing Th17 and mechanisms governing their differentiation provides valuable insights into the mechanisms underlying the dynamically changing statement of immune statement in health and diseases.

A growing number of studies have implicated that gut microbiota abundance is associated with myasthenia gravis (MG). However, the causal relationship underlying the associations is still unclear. Here, we aim to investigate the causal effect of gut microbiota on MG using Mendelian randomization (MR) method. Publicly available Genome-wide association study (GWAS) summary-level data for gut microbiota and for MG were extracted. Inverse variance weighted was used as the main method to analyze causality. The robustness of the results was validated with sensitivity analyses. Our results indicated that genetically predicted increased phylum Lentisphaerae (OR = 1.319, p = 0.026), class Lentisphaerae (OR = 1.306, p = 0.044), order Victivallales (OR = 1.306, p = 0.044), order Mollicutes (OR = 1.424, p = 0.041), and genus Faecalibacterium (OR = 1.763, p = 0.002) were potentially associated with a higher risk of MG; while phylum Actinobacteria (OR = 0.602, p = 0.0124), class Gammaproteobacteria (OR = 0.587, p = 0.036), family Defluviitaleaceae (OR = 0.695, p = 0.047), family Peptococcaceae (OR = 0.698, p = 0.029), and family Family XIII (OR = 0.614, p = 0.017) were related to a lower risk of MG. The present study provides genetic evidence for the causal associations between gut microbiota and MG, thus suggesting novel insights into the gut microbiota-neuromuscular junction axis in the pathogenesis of MG.

All-trans retinoic acid (ATRA) has emerged as a promising adjunctive treatment for rheumatoid arthritis. However, the mechanism by which ATRA mitigates arthritis remains unclear. In this study, we aimed to explore ATRA alleviation of arthritis and the role of ATRA in regulating intestinal homeostasis. Thus, we established a collagen-induced arthritis (CIA) model in Wistar rats. After 6 weeks of ATRA treatment, the arthritis index of CIA rats decreased, synovial inflammation was alleviated, and the disruption of Th17/Treg differentiation in peripheral blood was reversed. Additionally, the Th17/Treg ratio in the mesenteric lymph nodes decreased and the expression of Foxp3 mRNA increased and that of IL-17 mRNA decreased in the colon and ileum. Microscopically, we observed reduced intestinal inflammation. Transmission electron microscopy revealed that ATRA could repair tight junctions, which was accompanied by an increase in the expression of Claudin-1, Occludin and ZO-1. Moreover, ATRA regulated the composition of the gut microbiota, as was characterized based on the reduced abundance of Desulfobacterota and the increased abundance of Lactobacillus. In conclusion, ATRA demonstrates the potential to alleviate arthritis in CIA rats, which might be correlated with modulating the gut microbiota and regulating the intestinal immune response. Our findings provide novel insights into ATRA-mediated alleviation of arthritis.

Maternal immune activation (MIA), defined as elevated levels of inflammatory markers beyond the normal range, can occur due to psychological stress, infection, and other disruptions during pregnancy. MIA affects the immune system development in offspring and increases the risk of immune-related disorders. Limited studies have investigated the effects of prenatal stress on offspring's immune system. In this study, pregnant rats were exposed to chronic unpredictable mild stress (CUMS) during pregnancy, involving seven different stressors. We examined the impact of prenatal stress stimuli on the offspring's immune system and observed activation of the PI3K/Akt/NF-κB signaling pathway, resulting in an imbalance of Th17/Treg cells in the offspring's spleen. Our findings revealed increased plasma levels of corticosterone, IL-1β, and IL-6 in female rats exposed to prenatal stress, as well as elevated serum levels of IL-6 and TNF-α in the offspring. Furthermore, we identified a correlation between cytokine levels in female rats and their offspring. Transcriptome sequencing and qPCR experiments indicated differentially expressed mRNAs in offspring exposed to prenatal stress, which may contribute to the imbalance of Th17/Treg cells through the activation of the Gng3-related PI3K/Akt/NF-κB pathway.

Spinal cord injury (SCI) is devastating for patients, and currently lacks effective treatments. Dysbiosis commonly occurs after SCI and has significant immunomodulatory effects, but its impact on recovery remains unclear. The current study investigated the effects and mechanisms of fecal microbiota transplantation (FMT) in SCI. FMT was administered in a rat model of SCI and spinal pathology, inflammatory cytokines, and gut microbiome composition were assessed. Flow cytometry identified a source of interleukin (IL)-17 in spinal cord tissues, and carboxyfluorescein succimidyl ester labeling tracked γδ T cell migration. In vitro coculture was used to analyze the regulatory mechanisms of γδ T cells. Seahorse analysis was used to profile dendritic cell (DC) metabolism. Here we show that FMT improved spinal pathology and dampened post-injury inflammation. It also corrected post-SCI dysbiosis, increasing levels of the beneficial bacterium Akkermansia. The therapeutic effects of FMT were mediated by IL-17 produced by γδ T cells. FMT regulated γδ T cells via DC-T regulatory cell interaction, and induced metabolic reprogramming in DCs. These findings suggest that FMT represents a promising therapeutic approach for SCI, with potential to target IL-17+ γδ T cells. Elucidating the interconnected pathways between microbiota, immunity, and the spinal cord may facilitate novel treatment strategies.

Background: Glioblastoma (GBM) is the most prevalent malignant brain tumor, significantly impacting the physical and mental wellbeing of patients. Several studies have demonstrated a close association between gut microbiota and the development of GBM. In this investigation, Mendelian randomization (MR) was employed to rigorously evaluate the potential causal relationship between gut microbiota and GBM. Methods: We utilized summary statistics derived from genome-wide association studies (GWAS) encompassing 211 gut microbiota and GBM. The causal association between gut microbiota and GBM was scrutinized using Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Cochrane's Q statistic was employed to conduct a heterogeneity test. MR-Pleiotropic Residuals and Outliers (MR-PRESSO) were applied to identify and eliminate SNPs with horizontal pleiotropic outliers. Additionally, Reverse MR was employed to assess the causal relationship between GBM and pertinent gut microbiota. Results: The MR study estimates suggest that the nine gut microbiota remain stable, considering heterogeneity and sensitivity methods. Among these, the family.Peptostreptococcaceae and genus.Eubacterium brachy group were associated with an increased risk of GBM, whereas family.Ruminococcaceae, genus.Anaerostipes, genus.Faecalibacterium, genus.LachnospiraceaeUCG004, genus.Phascolarctobacterium, genus.Prevotella7, and genus.Streptococcus were associated with a reduced risk of GBM. Following Benjamini and Hochberg (BH) correction, family.Ruminococcaceae (OR = 0.04, 95% CI: 0.01-0.19, FDR = 0.003) was identified as playing a protective role against GBM. Conclusion: This groundbreaking study is the first to demonstrate that family.Ruminococcaceae is significantly associated with a reduced risk of GBM. The modulation of family_Ruminococcaceae for the treatment of GBM holds considerable potential clinical significance.

Chronic inflammation is associated with a prolonged increase in various inflammatory factors. According to clinical data, it can be linked with both cancer and autoimmune diseases in the same patients. This raises the critical question of how chronic inflammation relates to seemingly opposing diseases - tumors, in which there is immunosuppression, and autoimmune diseases, in which there is over-activation of the immune system. In this review, we consider chronic inflammation as a prerequisite for both immune suppression and an increased likelihood of autoimmune damage. We also discuss potential disease-modifying therapies targeting chronic inflammation, which can be helpful for both cancer and autoimmunity. On the one hand, pro-inflammatory factors persisting in the areas of chronic inflammation stimulate the production of anti-inflammatory factors due to a negative feedback loop, eliciting immune suppression. On the other hand, chronic inflammation can bring the baseline immunity closer to the threshold level required for triggering an autoimmune response using the bystander activation of immune cells. Focusing on the role of chronic inflammation in cancer and autoimmune diseases may open prospects for more intensive drug discovery for chronic inflammation.

Cells and tissues in an inflammatory state are usually hypoxic. The hypoxic environment can affect the differentiation of immune cells and produce Hypoxia-inducible Factor-1α (HIF-1α). Inflammation is also a major contributor to the development and deterioration of Myasthenia Gravis (MG). There are limited studies on the immunopathological mechanism and targeted therapy associated with MG exacerbated with inflammation. This research aimed to explore whether BAY 87-2243 (HIF-1α inhibitor) ameliorates the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model and study its regulatory mechanism on cellular immunity and humoral immunity.

We first establish the EAMG inflammation model using Lipopolysaccharide (LPS), BAY 87-2243 was applied to the EAMG inflammation model and its therapeutic effects were evaluated in vivo and in vitro experiments.

The proportion of Treg cells was increased whereas Th1, Th17, and Th1/17 cells were decreased in BAY 87-2243-treated EAMG inflammation model. BAY 87-2243 ameliorated the acetylcholine receptors (AChRs) loss and the complement deposited at the neuromuscular junction of the EAMG inflammation model, declined the levels of IFN-γ, IL-17, and IL-6 in serum, and further attenuated responses in the germinal center and reduced the antibody levels by inhibiting the IL-6-dependent STAT3 axis.

BAY 87-2243 restored the balance of CD4+T cell subsets and reduced the production of the pro-inflammatory cytokines, thus acting as both an immune imbalance regulator and anti-inflammatory. The current study suggests that HIF-1α might be a potential target for the treatment of MG exacerbated with inflammation.

The microbiota represents a key factor in determining health and disease. Its role in inflammation and immunological disorders is well known, but it is also involved in several complex conditions, ranging from neurological to psychiatric, from gastrointestinal to cardiovascular diseases. It has recently been hypothesized that the gut microbiota may act as an intermediary in the close interaction between kidneys and the cardiovascular system, leading to the conceptualization of the "gut-kidney-heart" axis. In this narrative review, we will discuss the impact of the gut microbiota on each system while also reviewing the available data regarding the axis itself. We will also describe the role of gut metabolites in this complex interplay, as well as potential therapeutical perspectives.

Fermented butyrate exhibits an anti-inflammatory response to maintain immune homeostasis within the gut. However, the effect and underlying mechanism of butyrate on myasthenia gravis (MG) remain unclear. The changes in the gut microbiota and fecal contents of SCFAs in MG patients were examined. R97-116 peptide was used to induce the experimental autoimmune myasthenia gravis (EAMG) mice and sodium butyrate (NaB) was gavaged to the EAMG mice. Gut microbiota, the frequency of Th1, Th17, Treg, Tfh, and B cells, the levels of IFN-γ, IL-17 A, IL-10, IL-21, and anti-R97-116 IgG, RNA-seq of total B cells in the spleen were explored by metagenomics, flow cytometry, ELISA, and transcriptomics. A significant reduction in SCFA-producing bacteria including Butyricimonas synergistica and functional modules including butyrate synthesis/production II was observed in MG patients and fecal SCFAs detection confirmed the increase. The EAMG mice were successfully constructed and NaB supplementation has changed the composition and function of the gut microbiota. The numbers of Th1, Th17, Tfh, and B cells were significantly increased while that of Treg cells was obviously decreased in EAMG mice compared with controls. Interestingly, NaB treatment has reduced the amounts of Th17, Tfh, and B cells but increased that of Treg cells. Accordingly, the levels of IL-17 A, IL-21, and IgG were increased while IL-10 was decreased in EAMG mice. However, NaB treatment reduced IL-17 A and IL-21 but increased that of IL-10. RNA-seq of B cells has revealed 4577 deferentially expressed genes (DEGs), in which 1218 DEGs were up-regulated while 3359 DEGs were down-regulated in NaB-treated EAMG mice. GO enrichment and KEGG pathway analysis unveiled that the function of these DEGs was mainly focused on immunoglobulin production, mitochondrial respiratory chain complex, ribosome, oxidative phosphorylation, and CNS diseases including amyotrophic lateral sclerosis. We have found that butyrate was significantly reduced in MG patients and NaB gavage could evidently improve MG symptoms in EAMG mice by changing the gut microbiota, regulating the immune response, and altering the gene expression and function of B cells, suggesting NaB might be a potential immunomodulatory supplement for MG drugs.

This bibliometric study aimed to summarize and visualize the current research status, emerging trends, and research hotspots of regulatory T (Treg) cells in neurological diseases. Relevant documents were retrieved from the Web of Science Core Collection. Tableau Public, VOSviewer, and CiteSpace software were used to perform bibliometric analysis and network visualization. A total of 2,739 documents were included, and research on Treg cells in neurological diseases is still in a prolific period. The documents included in the research were sourced from 85 countries/regions, with the majority of them originating from the United States, and 2,811 organizations, with a significant proportion of them coming from Harvard Medical School. Howard E Gendelman was the most prolific author in this research area. Considering the number of documents and citations, impact factors, and JCR partitions, Frontiers in Immunology was the most popular journal in this research area. Keywords "multiple sclerosis," "inflammation," "regulatory T cells," "neuroinflammation," "autoimmunity," "cytokines," and "immunomodulation" were identified as high-frequency keywords. Additionally, "gut microbiota" has recently emerged as a new topic of interest. The study of Treg cells in neurological diseases continues to be a hot topic. Immunomodulation, gut microbiota, and cytokines represent the current research hotspots and frontiers in this field. Treg cell-based immunomodulatory approaches have shown immense potential in the treatment of neurological diseases. Modifying gut microbiota or regulating cytokines to boost the numbers and functions of Treg cells represents a promising therapeutic strategy for neurological diseases.

Many studies have shown that gut microbiota is closely related to autoimmune diseases (ADs). Studies on gut microbiota and ADs have also increased significantly, but no bibliometric analysis has summarized the association between gut microbiota and ADs. This study aimed to conduct a bibliometric and visual analysis of published studies on gut microbiota and ADs. Based on the Web of Science Core Collection SCI-expanded database, we utilize Excel 2019 and visualization analysis tools VOSviewer and co-occurrence13.2 (COOC13.2) for analysis. A total of 2516 related kinds of literature were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is the USA, the institution is the Harvard Medical School, and the author is Mikael Knip from the USA. Hot research areas include intestinal regulation (such as dysbiosis, short chain fatty acids, and probiotics), multisystem ADs (such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease), and immune-related cells (such as T cells, and dendritic cells). Psoriasis, dysbiosis, autoimmune liver disease, and fecal microbiota transplantation may be the future research direction. Our research results can help researchers grasp the current status of ADs and gut microbiota research and find new research directions in the future.

Myasthenia gravis (MG) is a neuromuscular junction disease with a complex pathophysiology and clinical variation for which no clear biomarker has been discovered. We hypothesized that because changes in gut microbiome composition often occur in autoimmune diseases, the gut microbiome structures of patients with MG would differ from those without, and supervised machine learning (ML) analysis strategy could be trained using data from gut microbiota for diagnostic screening of MG. Genomic DNA from the stool samples of MG and those without were collected and established a sequencing library by constructing amplicon sequence variants (ASVs) and completing taxonomic classification of each representative DNA sequence. Four ML methods, namely least absolute shrinkage and selection operator, extreme gradient boosting (XGBoost), random forest, and classification and regression trees with nested leave-one-out cross-validation were trained using ASV taxon-based data and full ASV-based data to identify key ASVs in each data set. The results revealed XGBoost to have the best predicted performance. Overlapping key features extracted when XGBoost was trained using the full ASV-based and ASV taxon-based data were identified, and 31 high-importance ASVs (HIASVs) were obtained, assigned importance scores, and ranked. The most significant difference observed was in the abundance of bacteria in the Lachnospiraceae and Ruminococcaceae families. The 31 HIASVs were used to train the XGBoost algorithm to differentiate individuals with and without MG. The model had high diagnostic classification power and could accurately predict and identify patients with MG. In addition, the abundance of Lachnospiraceae was associated with limb weakness severity. In this study, we discovered that the composition of gut microbiomes differed between MG and non-MG subjects. In addition, the proposed XGBoost model trained using 31 HIASVs had the most favorable performance with respect to analyzing gut microbiomes. These HIASVs selected by the ML model may serve as biomarkers for clinical use and mechanistic study in the future. Our proposed ML model can identify several taxonomic markers and effectively discriminate patients with MG from those without with a high accuracy, the ML strategy can be applied as a benchmark to conduct noninvasive screening of MG.

The homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study.

Fecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS).

The microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels.

Our findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease and its pathogenesis is closely related to CD4 + T cells. In recent years, gut microbiota is considered to play an important role in the pathogenesis of MG. Astragaloside IV (AS-IV) is one of the main active components extracted from Astragalus membranaceus and has immunomodulatory effects. To study the immunomodulatory effect of AS-IV and the changes of gut microbiota on experimental autoimmune myasthenia gravis (EAMG) mice, we explore the possible mechanism of AS-IV in improving MG.

In this study, network pharmacology was utilized to screen the crucial targets of AS-IV in the treatment of MG. Subsequently, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to identify potential pathways through which AS-IV acts against MG. Furthermore, experimental investigations were conducted to validate the underlying mechanism of AS-IV in MG treatment. Before modeling, 5 mice were randomly selected as the control group (CFA group), and the other 10 were induced to EAMG model. These mice were randomly divided into EAMG group and EAMG + AS-IV group, n = 5/group. In EAMG + AS-IV group, AS-IV was administered by gavage. CFA and EAMG groups were given the same volume of PBS. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. At the last administration, the feces were collected for 16S RNA microbiota analysis. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected by flow cytometry. The levels of IFN-γ, IL-17 and TGF-β in serum were measured by ELISA. Furthermore, fecal microbial transplantation (FMT) experiments were performed for exploring the influence of changed intestinal flora on EAMG. After EAMG model was induced, the mice were treated with antibiotics daily for 4 weeks to germ-free. Then germ-free EAMG mice were randomly divided into two groups: FMT EAMG group, FMT AS-IV group, n = 3/group. Fecal extractions from EAMG and EAMG + AS-IV groups as gathered above were used to administered daily to the respective groups for 4 weeks. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected at the last administration. The levels of IFN-γ, IL-17 and TGF-β in serum were measured by ELISA.

The network pharmacology and KEGG pathway analysis revealed that AS-IV regulates T cell pathways, including T cell receptor signaling pathway and Th17 cell differentiation, suggesting its potential in improving MG. Further experimental verification demonstrated that AS-IV administration improved muscle strength and body weight, reduced the level of Th1 and Th17 cells, enhanced the level of Treg cells, and resulted in alterations of the gut microbiota, including changes in beta diversity, the Firmicutes/Bacteroidetes (F/B) ratio, and the abundance of Clostridia in EAMG mice. We further conducted FMT tests and demonstrated that the EAMG Abx-treated mice which were transplanted the feces of mice treated with AS-IV significantly alleviated myasthenia symptoms, reduced Th1 and Th17 cells levels, and increased Treg cell levels.

This study speculated that AS-IV ameliorates EAMG by regulating CD4 + T cells and altering the structure and species of gut microbiota of EAMG.

Inflammatory bowel disease (IBD) is a complex multifactorial chronic inflammatory disease, that includes Crohn's disease (CD) and ulcerative colitis (UC), having progressively increasing global incidence. Disturbed intestinal flora has been highlighted as an important feature of IBD and offers promising strategies for IBD remedies. A brief overview of the variations occurring in intestinal flora during IBD is presented, and the role of the gut microbiota in intestinal barrier maintenance, immune and metabolic regulation, and the absorption and supply of nutrients is reviewed. More importantly, we review drug research on gut microbiota in the past ten years, including research on clinical and natural drugs, as well as adjuvant therapies, such as Fecal Microbiota Transplantation and probiotic supplements. We also summarize the interventions and mechanisms of these drugs on gut microbiota.

Integrity of the microbiome is an essential element for human gut health. 3-Hydroxybutyrate (3HB) secreted into the gut lumen has gained attention as a regulator of gut physiology, including stem cell expansion. In this opinion, I propose new prebiotics leading to gut health by use of a ketone (3HB) donor. When exogenous 3HB is supplied through ketone donation, it has the potential to markedly improve gut health by altering the gut microbiome and systemic metabolic status. Poly-hydroxybutyrate (PHB) donates 3HB and primarily influences microbiota, making it an effective prebiotic for improving the gut environment. Thus, exogenous 3HB donation to the lumen of the gut may aid gut health by maintaining the integrity of microbiome.

The gut microbiota colonizing the gastrointestinal tract, is an indispensable "invisible organ" that affects multiple aspects of human health. The gut microbial community has been assumed to be an important stimulus to the immune homeostasis and development, and increasing data support the role of the gut microbiota-immunity axis in autoimmune diseases. Host's immune system requires recognition tools to communicate with the gut microbial evolutionary partners. Among these microbial perceptions, T cells enable the widest spectrum of gut microbial recognition resolution. Specific gut microbiota direct the induction and differentiation of Th17 cells in intestine. However, the detailed links between the gut microbiota and Th17 cells have not been well established. In this review, we describe the generation and characterization of Th17 cells. Notably, we discuss the induction and differentiation of Th17 cells by the gut microbiota and their metabolites, as well as recent advances in our understanding of interactions between Th17 cells and the gut microbiota in human diseases. In addition, we provide the emerging evidences in support of interventions targeting the gut microbes/Th17 cells in human diseases.

It has been widely demonstrated that the gut microbiota is responsible for essential functions in human health and that its perturbation is implicated in the development and progression of a growing list of diseases. The number of studies evaluating how the gut microbiota interacts with and influences other organs and systems in the body and vice versa is constantly increasing and several 'gut-organ axes' have already been defined. Recently, the view on the link between the gut microbiota (GM) and the peripheral nervous system (PNS) has become broader by exceeding the fact that the PNS can serve as a systemic carrier of GM-derived metabolites and products to other organs. The PNS as the communication network between the central nervous system and the periphery of the body and internal organs can rather be affected itself by GM perturbation. In this review, we summarize the current knowledge about the impact of gut microbiota on the PNS, with regard to its somatic and autonomic divisions, in physiological, regenerative and pathological conditions.

In recent years, epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis. The question arises whether patients with schizophrenia are more likely to develop multiple sclerosis (MS) later in life. It is well known that the immune system plays an important role in the etiopathogenesis of both disorders. Immune disturbances may be similar or very different in terms of different types of immune responses, disturbed myelination, and/or immunogenetic predispositions. A psychotic symptom may be a consequence of the MS diagnosis itself or a separate entity. In this review article, we discussed the timing of onset of psychotic symptoms and MS and whether the use of corticosteroids as therapy for acute relapses in MS is unfairly neglected in patients with psychiatric comorbidities. In addition, we discussed that the anti-inflammatory potential of antipsychotics could be useful and should be considered, especially in the treatment of psychosis that coexists with MS. Autoimmune disorders could precipitate psychotic symptoms, and in this context, autoimmune psychosis must be considered as a persistent symptomatology that requires continuous and specific treatment.

The liver is frequently exposed to potentially toxic materials, and it is the primary site of clearance of foreign agents, along with many innate and adaptive immune cells. Subsequently, drug induced liver injury (DILI), which is caused by medications, herbs, and dietary supplements, often occurs and has become an important issue in liver diseases. Reactive metabolites or drug-protein complexes induce DILI via the activation of various innate and adaptive immune cells. There has been a revolutionary development of treatment drugs for hepatocellular carcinoma (HCC) and liver transplantation (LT), including immune checkpoint inhibitors (ICIs), that show high efficacy in patients with advanced HCC. Along with the high efficacy of novel drugs, DILI has become a pivotal issue in the use of new drugs, including ICIs. This review demonstrates the immunological mechanism of DILI, including the innate and adaptive immune systems. Moreover, it aims to provide drug treatment targets, describe the mechanisms of DILI, and detail the management of DILI caused by drugs for HCC and LT.

T Helper 17 (Th17) cells are adaptive immune cells that play myriad roles in the body. Immune-endocrine interactions are vital in endocrine organs during pathological states. Th17 cells are known to take part in multiple autoimmune diseases over the years. Current evidence has moved from minimal to substantial that Th17 cells are closely related to endocrine organs. Diverse tissue Th17 cells have been discovered within endocrine organs, including gut, adipose tissue, liver and bone, and these cells are modulated by various secretions from endocrine organs. Th17 cells in these endocrine organs are key players in the process of an array of metabolic disorders and inflammatory conditions, including obesity, insulin resistance, nonalcoholic fatty liver disease (NAFLD), primary sclerosing cholangitis (PSC), osteoporosis and inflammatory bowel disease (IBD). We reviewed the pathogenetic or protective functions played by Th17 cells in various endocrine tissues and identified potential regulators for plasticity of it. Furthermore, we discussed the roles of Th17 cells in crosstalk of gut-organs axis.

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies that is dependent on T-cell immunity and complement participation and mainly involves neuromuscular junctions. In this study, 30 patients with myasthenia gravis were selected and divided into pretreatment (Case group) and posttreatment (Treatment group) and 30 healthy volunteers (CON group) were included. Among them, the treatment group was treated with Modified Buzhong Yiqi Decoction (MBZYQD), and the levels of antibodies such as AChR, Musk and Titin in blood and intestinal microbiota were compared before treatment (Case group), after treatment (Treatment group) and in healthy volunteers (CON group). The results showed that after treatment with MBZYQD, the antibody levels of AChR, MuSK, and Titin and the inflammatory factor level of IL-6, IL-1β, and IL-22 in MG patients decreased significantly and nearly returned to a healthy level. In addition, after treatment with MBZYQD, the diversity, structure and function of intestinal microorganisms in MG patients also recovered to a healthy level. At the phylum level, the relative abundance of Proteobacteria in the Case group increased significantly, accompanied by a significant decrease in the relative abundance of Bacteroides compared with that in the CON group, the relative abundance of Proteobacteria and Bacteroides in the Treatment group was similar to that in the CON group. At the genus level, the relative abundance of Shigella in the Case group was significantly increased, accompanied by a significant decrease in the relative abundance of Prevotella, and the relative abundance of Shigella and Prevotella in Treatment group was similar to that in the CON group. Moreover, the fluorobenzoate degradation pathway (KO00364) was significantly increased in the Case group, while this pathway was significantly decreased in the Treatment group. In conclusion, MBZYQD can improve the immune function of the host by regulating the diversity, structure and function of the intestinal microbiota to treat myasthenia gravis.

Myasthenia gravis (MG) is an acquired neurological autoimmune disorder characterized by dysfunctional transmission at the neuromuscular junction. The complex interplay of genetic and environmental influences is important for the occurrence and development of the disease. Recently, some studies have demonstrated the relationship between gut microbiota dysbiosis and MG. Certain gut microbial strains have been shown to attenuate or promote MG. This review summarized the role of gut microbiota and metabolites in MG progression. Meanwhile, we discuss the important potential of gut microbiota and metabolites for the early diagnostic biomarker of MG. Regulating gut microbiota may be novel and effective treatment for MG. Thus, targeted gut microbiota therapies are discussed and prospected to prevent MG progression.

Two of the molecular families closely associated with mediating communication between the brain and immune system are cytokines and the kynurenine metabolites of tryptophan. Both groups regulate neuron and glial activity in the central nervous system (CNS) and leukocyte function in the immune system, although neither group alone completely explains neuroimmune function, disease occurrence or severity. This essay suggests that the two families perform complementary functions generating an integrated network. The kynurenine pathway determines overall neuronal excitability and plasticity by modulating glutamate receptors and GPR35 activity across the CNS, and regulates general features of immune cell status, surveillance and tolerance which often involves the Aryl Hydrocarbon Receptor (AHR). Equally, cytokines and chemokines define and regulate specific populations of neurons, glia or immune system leukocytes, generating more specific responses within restricted CNS regions or leukocyte populations. In addition, as there is a much larger variety of these compounds, their homing properties enable the superimposition of dynamic variations of cell activity upon local, spatially limited, cell populations. This would in principle allow the targeting of potential treatments to restricted regions of the CNS. The proposed synergistic interface of 'tonic' kynurenine pathway affecting baseline activity and the superimposed 'phasic' cytokine system would constitute an integrated network explaining some features of neuroimmune communication. The concept would broaden the scope for the development of new treatments for disorders involving both the CNS and immune systems, with safer and more effective agents targeted to specific CNS regions.