Search

Aims. The neuropeptide galanin is a widely distributed neurotransmitter/neuromodulator that regulates a variety of physiological processes and also participates in the regulation of stress responses. The aims of the present study were to investigate the expression of galanin receptors (GalR1, GalR2, GalR3) in the spinal cords in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) using qPCR analysis and to determine GalR1 cellular localization (oligodendrocytes, microglia, astrocytes, ependymal cells, and endothelial cells in the capillaries) by immunohistochemistry. Methods. Twelve samples from the EAE group and 14 samples from the control group were analyzed. Spinal cords samples were obtained at the peak of the EAE disease. Results. The GalR1 mRNA level was significantly decreased in the EAE mice compared with the controls (P=0.016), whereas the mRNA levels of GalR2 and GalR3 were not significantly different for the EAE and the control mice. No significant correlations were found between the severity of the EAE disease and the mRNA levels of GalR1, GalR2 and GalR3. Immunochemical detection of the GalR1 revealed its expression in the ependymal and endothelial cells. Additionally, a weak GalR1 immunoreactivity was occasionally detected in the oligodendrocytes. Conclusion. This study provides additional evidence of galanin involvement in EAE pathophysiology, but this has to be further investigated. [ABSTRACT FROM AUTHOR]

Abstract Background Ankylosing enthesopathy (ANKENT) is an animal model of human ankylosing spondylitis. ANKENT is an inflammatory disease affecting the ankle and tarsal joints of the hind limbs in susceptible mouse strains. In the disease, the participation of intestinal microbiota components was suggested. Therefore, we attempted to increase the incidence of ANKENT by systemic administration of lipopolysaccharide (LPS), which is a component of bacterial cellular walls and stimulates inflammatory processes. Methods ANKENT occurrence, serum cytokine profiles, spleen cellular composition and in vitro cytokine response to LPS were analysed in LPS-treated and control LPS-untreated B10.BR male mice. Results Contrary to expectations, LPS treatment decreased the incidence of ANKENT in LPS-treated group compared to control LPS-untreated group. Flow cytometry analysis of splenocytes showed an increased percentage of macrophages, dendritic cells and neutrophils and a decreased percentage of B cells, T cells and T helper cells in LPS-treated males following LPS administration. In addition, LPS-treated males had significantly elevated IL-6 and IL-10 serum levels. At 20–22 weeks after the final LPS application, splenocytes from LPS-treated mice were more susceptible to in vitro LPS stimulation than those of the controls and produced significantly higher levels of TNFα and IL-6. Conclusions Repeated systemic stimulation with microbial component lipopolysaccharide in early adulthood significantly reduced the incidence of ANKENT in B10.BR mice and this finding can support the “hygiene hypothesis”. In LPS-treated mice, the innate immunity parameters and the level of anti-inflammatory IL-10 cytokine were significantly increased. Nevertheless, the immunological mechanism of the LPS protective effect remains unclear.

Abstract Background Mammals are essentially born germ-free but the epithelial surfaces are promptly colonized by astounding numbers of bacteria soon after birth. The most extensive microbial community is harbored by the distal intestine. The gut microbiota outnumber ~10 times the total number of our somatic and germ cells. The host-microbiota relationship has evolved to become mutually beneficial. Studies in germ-free mice have shown that gut microbiota play a crucial role in the development of the immune system. The principal aim of the present study was to elucidate whether the presence of gut microbiota and the quality of a sterile diet containing various amounts of bacterial contaminants, measured by lipopolysaccharide (LPS) content, can influence maturation of the immune system in gnotobiotic mice. Results We have found that the presence of gut microbiota and to a lesser extent also the LPS-rich sterile diet drive the expansion of B and T cells in Peyer's patches and mesenteric lymph nodes. The most prominent was the expansion of CD4+ T cells including Foxp3-expressing T cells in mesenteric lymph nodes. Further, we have observed that both the presence of gut microbiota and the LPS-rich sterile diet influence in vitro cytokine profile of spleen cells. Both gut microbiota and LPS-rich diet increase the production of interleukin-12 and decrease the production of interleukin-4. In addition, the presence of gut microbiota increases the production of interleukin-10 and interferon-γ. Conclusion Our data clearly show that not only live gut microbiota but also microbial components (LPS) contained in sterile diet stimulate the development, expansion and function of the immune system. Finally, we would like to emphasize that the composition of diet should be regularly tested especially in all gnotobiotic models as the LPS content and other microbial components present in the diet may significantly alter the outcome of experiments.

A simple straightforward method for fabrication of patterns of metallic nanostructures and the application of focused ion beam (FIB) lithography to locally modify a native Si[O.sub.2] layer on a silicon substrate are described. The results proposed that the island formation at patterned sites are due to reduced surface diffusion of Co atoms in the vicinity of FIB modified areas and the lowered kinetic diffusion limits improved the island morphology.

The world-wide incidence of many immune-mediated and metabolic diseases, including those of the intestines and liver, is steadily increasing. Gut microbiota plays a central role in the pathogenesis of these diseases as it mediates environmental changes to the intestinal immune system. Various environmental factors including diet, food additives and medication also trigger the compositional and functional alterations of microbiota, that is, dysbiosis, and this dysbiosis is closely associated with many chronic inflammatory diseases. However, the causal relationship remains unclear for the majority of these diseases. In this review, we discuss essential epidemiological data, known pathogenetic factors including those of genetic and environmental nature, while mainly focusing on the role of gut microbiota in the development of selected intestinal and liver diseases. Using specific examples, we also briefly describe some of the most widely-used animal models including gnotobiotic models and their contribution to the research of pathogenetic mechanisms of the host–microbiota relationship. [ABSTRACT FROM AUTHOR]

A healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases. However, it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, commensal bacteria-dependent colitis model in IL-10-deficient mice, we investigated the role of TLR and their negative regulation in intestinal homeostasis. In addition to IL-10 [ABSTRACT FROM AUTHOR]

In this paper, we aimed to characterize the fecal microbiome and its resistomes of healthy and diseased subjects infected with multidrug-resistant Escherichia coli using next-generation sequencing (NGS). After initial screening, 26 stools samples belonging to healthy (n = 13) and diseased subjects (n = 13) were selected and subjected to NGS. A total of 23 and 42 antibiotic-resistant genes (ARGs) conferring resistance to 6 and 9 classes of antibiotics were identified in the resistomes of healthy and diseased subjects, respectively. Bacteroidetes were found to be the major phylum in both healthy and diseased subjects; however, Proteobacteria was predominantly present in the diseased subjects only. Microbial dysbiosis and predominance of various ARGs in the resistome of diseased subjects reflect the excessive usage of antibiotics in Pakistan and warrants immediate attention to regulate the use of various antimicrobials. [ABSTRACT FROM AUTHOR]

Obesity is a major public health problem that continues to be one of the leading risk factors for premature death. Early life is a critical period of time when the gut microbiota and host metabolism are developing in tandem and significantly contribute to long-term health outcomes. Dysbiosis of the gut microbiota, particularly in early life, can have detrimental effects on host health and increase the susceptibility of developing obesity later in life. Antibiotics are an essential lifesaving treatment; however, their use in early life may not be without risk. Antibiotics are a leading cause of intestinal dysbiosis, and early life administration is associated with obesity risk. The following review explores the relevant literature that simultaneously examines antibiotic-induced dysbiosis and obesity risk. Current evidence suggests that disruptions to the composition and maturation of the gut microbiota caused by antibiotic use in early life are a key mechanism linking the association between antibiotics and obesity. Without compromising clinical practice, increased consideration of the long-term adverse effects of antibiotic treatment on host health, particularly when used in early life is warranted. Novel adjunct interventions should be investigated (e.g., prebiotics) to help mitigate metabolic risk when antibiotic treatment is clinically necessary. [ABSTRACT FROM AUTHOR]

Kale (Brassica oleracea var. acephala) is a vegetable common in most cultures but is less studied as a functional food compared to other cruciferous vegetables, such as broccoli. We investigated the effect of supplementing a high-fat diet (HFD) with kale (HFKV) in C57BL/6J mice. We particularly explored its role in metabolic parameters, gut bacterial composition and diversity using 16S rRNA sequencing, systematically compared changes under each phylum and predicted the functional potential of the altered bacterial community using PICRUSt2. Like other cruciferous vegetables, kale attenuated HFD-induced inflammation. In addition, kale modulated HFD-induced changes in cecal microbiota composition. The HFD lowered bacterial diversity, increased the Firmicutes: Bacteroidetes (F/B) ratio and altered composition. Specifically, it lowered Actinobacteria and Bacteroidetes (Bacteroidia, Rikenellaceae and Prevotellaceae) but increased Firmicutes (mainly class Bacilli). Kale supplementation lowered the F/B ratio, increased both alpha and beta diversity and reduced class Bacilli and Erysipelotrichi but had no effect on Clostridia. Within Actinobacteria, HFKV particularly increased Coriobacteriales/Coriobacteriaceae about four-fold compared to the HFD (p < 0.05). Among Bacteroidia, HFKV increased the species Bacteroides thetaiotaomicron by over two-fold (p = 0.05) compared to the HFD. This species produces plant polysaccharide digesting enzymes. Compared to the HFD, kale supplementation enhanced several bacterial metabolic functions, including glycan degradation, thiamine metabolism and xenobiotic metabolism. Our findings provide evidence that kale is a functional food that modulates the microbiota and changes in inflammation phenotype. [ABSTRACT FROM AUTHOR]

Non-infectious uveitis is considered an autoimmune disease responsible for a significant burden of blindness in developed countries and recent studies have linked its pathogenesis to dysregulation of the gut microbiota. We tested the immunomodulatory properties of two probiotics, Escherichia coli Nissle 1917 (EcN) and E. coli O83:K24:H31 (EcO), in a model of experimental autoimmune uveitis (EAU). To determine the importance of bacterial viability and treatment timing, mice were orally treated with live or autoclaved bacteria in both preventive and therapeutic schedules. Disease severity was assessed by ophthalmoscopy and histology, immune phenotypes in mesenteric and cervical lymph nodes were analyzed by flow cytometry and the gut immune environment was analyzed by RT-PCR and/or gut tissue culture. EcN, but not EcO, protected against EAU but only as a live organism and only when administered before or at the time of disease induction. Successful prevention of EAU was accompanied by a decrease in IRBP-specific T cell response in the lymph nodes draining the site of immunization as early as 7 days after the immunization and eye-draining cervical lymph nodes when the eye inflammation became apparent. Furthermore, EcN promoted an anti-inflammatory response in Peyer's patches, increased gut antimicrobial peptide expression and decreased production of inducible nitric oxide synthase in macrophages. In summary, we show here that EcN controls inflammation in EAU and suggest that probiotics may have a role in regulating the gut–eye axis. [ABSTRACT FROM AUTHOR]

The worldwide incidence of many immune-mediated and metabolic diseases, initially affecting only the wealthy Western countries, is increasing rapidly. Many of these diseases are associated with the compositional and functional alterations of gut microbiota, i.e., dysbiosis. The most consistent markers of the dysbiosis are a decrease in microbiota diversity and an expansion of Proteobacteria. The role of food preservatives as potential triggers of gut microbiota dysbiosis has been long overlooked. Using a human microbiota-associated mouse model, we demonstrate that a mixture of common antimicrobial food additives induces dysbiosis characterised by an overgrowth of Proteobacteria phylum and a decrease in the Clostridiales order. Remarkably, human gut microbiota in a Nod2-deficient genetic background is even more susceptible to the induction of Proteobacteria dysbiosis by additives than the microbiota in a wild-type background. To conclude, our data demonstrate that antimicrobial food additives trigger gut microbiota dysbiosis in both wild-type and Nod2-deficient backgrounds and at the exposure levels reached in European populations. Whether this additive-modified gut microbiota plays a significant role in the pathogenesis of immune-mediated and metabolic diseases remains to be elucidated. [ABSTRACT FROM AUTHOR]

An abstract of the medical research "THE IMPACT OF RECOMBINANT LACTOBACILLUS PLANTARUM ON POLLEN ALLERGY DEVELOPMENT," by Martin Schwarzer, Andreas Repa, Ursula Wiedermann, Tomas Hrncir, Catherine Daniel, Bruno Pot, Renata Stepankova, Tomas Hudcovic, Helena Tlaskalova-Hogenova, Martina Souckova and Hana Kozakova is presented.

Background: The aim was to analyze the influence of intestinal microbiota on the development of intestinal inflammation. We used the model of chronic inflammation that develops spontaneously in the colon of conventional severe combined immunodeficiency (SCID) mice restored with the CD45 RB(high) subset of CD4+T cells isolated from the spleen of normal BALB/c mice., Methods: A CD4+CD45RB(high) subpopulation of T cells was purified from the spleen of conventional BALB/c mice by magnetic separation (MACS) and transferred into immunodeficient SCID mice. Germ-free (GF) SCID mice or SCID mice monoassociated with Enterococcus faecalis, SFB (segmented filamentous bacteria), Fusobacterium mortiferum, Bacteroides distasonis, and in combination Fusobacterium mortiferum + SFB or Bacteroides distasonis + SFB were used as recipients. SCID mice were colonized by a defined cocktail of specific pathogen-free (SPF) bacteria. Mice were evaluated 8-12 weeks after the cell transfer for clinical and morphological signs of inflammatory bowel disease (IBD)., Results: After the transfer of the CD4+CD45RB(high) T-cell subpopulation to SCID mice severe colitis was present in conventional animals and in mice colonized with a cocktail of SPF microflora plus SFB. Altered intestinal barrier in the terminal ileum of mice with severe colitis was documented by immunohistology using antibodies to ZO-1 (zona occludens)., Conclusions: Only SFB bacteria together with a defined SPF mixture were effective in triggering intestinal inflammation in the model of IBD in reconstituted SCID mice, while no colitis was detected in GF mice or in mice colonized either with SPF microflora or monoassociated only with SFB or colonized by Bacteroides distasonis + SFB or Fusobacterium mortiferum + SFB.