/pdf/the-toll-like-receptor-2-pathway-establishes-colonization-by-2mfxvhffq2.pdf

The Toll-Like Receptor 2 pathway Establishes Colonization by a Commensal of the Human Microbiota

Vitamins are micronutrients that have physiological effects on various biological responses, including host immunity. Therefore, vitamin deficiency leads to increased risk of developing infectious, allergic, and inflammatory diseases. Since B vitamins are synthesized by plants, yeasts, and bacteria, but not by mammals, mammals must acquire B vitamins from dietary or microbial sources, such as the intestinal microbiota. Similarly, some intestinal bacteria are unable to synthesize B vitamins and must acquire them from the host diet or from other intestinal bacteria for their growth and survival. This suggests that the composition and function of the intestinal microbiota may affect host B vitamin usage and, by extension, host immunity. Here, we review the immunological functions of B vitamins and their metabolism by intestinal bacteria with respect to the control of host immunity.

/pdf/metabolism-of-dietary-and-microbial-vitamin-b-family-in-the-558tzngp4v.pdf

Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity

Dysbiosis of gut microbiota and microbial metabolites in Parkinson's Disease.

The gut microbiota is a highly complex community which evolves and adapts to its host over a lifetime. It has been described as a virtual organ owing to the myriad of functions it performs, including the production of bioactive metabolites, regulation of immunity, energy homeostasis and protection against pathogens. These activities are dependent on the quantity and quality of the microbiota alongside its metabolic potential, which are dictated by a number of factors, including diet and host genetics. In this regard, the gut microbiome is malleable and varies significantly from host to host. These two features render the gut microbiome a candidate ‘organ’ for the possibility of precision microbiomics—the use of the gut microbiome as a biomarker to predict responsiveness to specific dietary constituents to generate precision diets and interventions for optimal health. With this in mind, this two-part review investigates the current state of the science in terms of the influence of diet and specific dietary components on the gut microbiota and subsequent consequences for health status, along with opportunities to modulate the microbiota for improved health and the potential of the microbiome as a biomarker to predict responsiveness to dietary components. In particular, in Part I, we examine the development of the microbiota from birth and its role in health. We investigate the consequences of poor-quality diet in relation to infection and inflammation and discuss diet-derived microbial metabolites which negatively impact health. We look at the role of diet in shaping the microbiome and the influence of specific dietary components, namely protein, fat and carbohydrates, on gut microbiota composition.

Precision Nutrition and the Microbiome, Part I: Current State of the Science.

Microplastics and the gut microbiome: How chronically exposed species may suffer from gut dysbiosis.

The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease development. The gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses, influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.

/pdf/interaction-between-the-gut-microbiome-and-mucosal-immune-52p0bbi51i.pdf

Interaction between the gut microbiome and mucosal immune system.

The star target in SLE: IL-17

BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) incidence is higher in systemic lupus erythematosus (SLE) patients than the general population, but the molecular mechanisms behind this link remain ambiguous. The aim of this study was to investigate shared gene signatures and molecular pathways between SLE and DLBCL.


METHODS
We procured expression profiles of SLE and DLBCL from public databases and identified common differentially expressed genes (DEGs). Functional pathway enrichment and protein-protein interaction (PPI) analyses were performed on these shared genes. The molecular complex detection technology (MCODE) and eXtreme Gradient Boosting (XGBoost) machine learning algorithm were used to select core shared genes, followed by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis.


RESULTS
We identified 54 DEGs as shared genes, among which CD177, CEACAM1, GPR84 and IFIT3 were identified as core shared genes. These genes showed strong associations with inflammatory and immune response pathways. We found a significant positive correlation between GPR84 and IFIT3 expression levels and the immune microenvironment. Decreased expression levels of GPR84 and IFIT3 were linked to enhanced immune therapy sensitivity, potentially due to lower dysregulation scores during low expression. We also discovered that TP53 mutations might elevate CD177 and GPR84 expression and that reduced expression levels of GPR84 and IFIT3 were linked with better overall survival and progression-free survival in DLBCL patients.


CONCLUSIONS
Our study provides valuable insights into the shared molecular mechanisms underpinning the pathogenesis of SLE and DLBCL. These findings could potentially offer new biomarkers and therapeutic targets for SLE and DLBCL.

Identification of the shared gene signatures and molecular pathways in systemic lupus erythematosus and diffuse large B-cell lymphoma.

OBJECTIVE
To evaluate the efficacy and safety of telitacicept in adult patients with primary Sjögren's syndrome (pSS) in a phase II randomized double-blind placebo-controlled trial.


METHODS
Patients with pSS with positive anti-SSA antibody and ESSDAI ≥ 5 were randomly assigned, in a 1:1:1 ratio, to receive weekly subcutaneous telitacicept 240 mg, 160 mg, or placebo for 24 weeks. The primary end point was the change from baseline in the ESSDAI at week 24. Safety was monitored.


RESULTS
42 patients were enrolled and randomized (n = 14 per group). Administration of telitacicept 160 mg resulted in a significant reduction in ESSDAI score from baseline to week 24 compared with placebo (p< 0.05). The placebo-adjusted least-squares mean change from baseline was -4.3 (95% CI -7.0 to -1.6; p= 0·002). While, mean change of ESSDAI in telitacicept 240 mg was -2.7(-5.6-0.1) with no statistical difference when compared that in placebo group (p= 0.056). In addition, MFI-20 and serum immunoglobulins decreased significantly(p< 0.05) at week 24 in both telitacicept groups compared with placebo. No serious adverse events were observed in the telitacicept treating group.


CONCLUSION
Telitacicept showed clinical benefits and well tolerance and safety in the treatment of pSS.


CLINICAL TRIAL REGISTRATION NUMBER
ClinicalTrials.gov, https://clinicaltrials.gov, NCT04078386.

Xinwang Duan

Papers

Interaction between the gut microbiome and mucosal immune system.

The star target in SLE: IL-17

Identification of the shared gene signatures and molecular pathways in systemic lupus erythematosus and diffuse large B-cell lymphoma.

Efficacy and safety of telitacicept in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled, phase 2 trial.