Microbiota-Immunity Axis in the Different Pathological Disorders

Molecular mimicry, a phenomenon in which microbial or environmental antigens resemble host antigens, has been proposed as a potential trigger for autoimmune responses. In this study, we employed a bioinformatics approach to investigate the role of molecular mimicry in Clostridioides difficile-caused infections and the induction of autoimmune disorders due to this phenomenon. Comparing proteomes of host and pathogen, we identified 23 proteins that exhibited significant sequence homology and were linked to autoimmune disorders. The disorders included rheumatoid arthritis, psoriasis, Alzheimer’s disease, etc., while infections included viral and bacterial infections like HIV, HCV, and tuberculosis. The structure of the homologous proteins was superposed, and RMSD was calculated to find the maximum deviation, while accounting for rigid and flexible regions. Two sequence mimics (antigenic, non-allergenic, and immunogenic) of ≥10 amino acids from these proteins were used to design a vaccine construct to explore the possibility of eliciting an immune response. Docking analysis of the top vaccine construct C2 showed favorable interactions with HLA and TLR-4 receptor, indicating potential efficacy. The B-cell and T-helper cell activity was also simulated, showing promising results for effective immunization against C. difficile infections. This study highlights the potential of C. difficile to trigger autoimmunity through molecular mimicry and vaccine design based on sequence mimics that trigger a defensive response. Full article

Pachymaran (PCP), the major medicinal constituent of Poria cocos, has a regulatory effect on immunosuppressive lung injury, but its mechanism of action with respect to gut microorganisms and their metabolites is not clear. The aim of this study was to investigate the protective effect of PCP against immunosuppressive lung injury caused by cyclosporine A (CsA), and to reveal its possible mechanism of action via the comprehensive analysis of 16S rRNA and LC-MS. We demonstrated that PCP was effective at alleviating CsA-induced immunosuppressive lung injury by restoring the organ indices and lung tissue morphology and structure. PCP significantly altered the composition of the gut and lung microbiota in mice with CsA-induced immunosuppressive lung injury by increasing the number of beneficial bacteria from the Eubacterium nodatum group, Eubacterium ventriosum group, Akkermansia, and Ruminococcus, and reducing the pathogenic Rikenellaceae RC9 gut group to fulfill its immunomodulatory role. In lung tissue microecology, PCP intervention significantly reduced the abundance of Chryseobacterium, Lawsonella, Paracoccus, and Sediminibacterium and increased the abundance of Alloprevotella. The LC-MS results showed that PCP alleviated the CsA-induced immunosuppression of lung tissue injury. The model serum metabolite Americine decreased the expression of PC(O-18:1(4Z)/0:0). Our results suggest that PCP may be involved in regulating the composition, function, and metabolism of the gut and lung microbiota to reverse CsA-induced immunosuppressive lung injury. Full article

The human gastrointestinal tract hosts a complex and dynamic population of commensal bacterial species, which have coevolved with the host, generating a symbiotic relationship. Some compounds present in foods, such as polyols, prebiotic fibers, or phenolic compounds, are poorly metabolized and absorbed by the host before the transformation guided by the colonic microbiota. By influencing gut microbiota, diet plays a fundamental role in understanding the beneficial effects of the gut microbiota on the host, including its long-term metabolism. The idea that probiotics can act not only by influencing the colonizing microbiota opens the door to a wider range of probiotic possibilities, encouraging innovation in the field. Furthermore, it has been shown both that some probiotics increase phagocytosis or the activity of natural killer cells. Current prebiotics are mainly based on carbohydrates, but other substances, such as polyphenols and polyunsaturated fatty acids, could exert prebiotic effects. A prebiotic substance has been defined as ‘a substrate that is selectively used by host microorganisms that confer a health benefit’, and so can interact with the gut microbiota through competition for nutrients, antagonism, cross-feeding, and support for microbiota stability. Influencing its composition in terms of richness and diversity, food components have a key impact on the intestinal microbiota. Eating habits can strongly influence the composition of the intestinal microbiota. A healthy intestinal microbiota is essential for maintaining general health, and diet is one of the major modulators of this fascinating world of microorganisms. This must give us one more reason to adopt a healthy lifestyle. Full article