Nissan Yissachar's research while affiliated with Bar Ilan University and other places
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Publications (18)
Background: Parkinson disease (PD) is associated with dysbiosis, proinflammatory gut microbiome, disruptions to intestinal barrier functions, and immunological imbalance. Microbiota-produced short-chain fatty acids promote gut barrier integrity and immune regulation, but their impact on PD pathology remains mostly unknown.
Objectives: To evaluate s...
The intestinal epithelial barrier facilitates homeostatic host–microbiota interactions and immunological tolerance. However, mechanistic dissections of barrier dynamics following luminal stimulation pose a substantial challenge. Here, we describe an ex vivo intestinal permeability assay, X-IPA, for quantitative analysis of gut permeability dynamics...
The intestinal epithelial barrier facilitates homeostatic host-microbiota interactions and immunological tolerance. However, mechanistic dissections of barrier dynamics following luminal stimulation pose a substantial challenge. Here, we describe an ex-vivo intestinal permeability assay, X-IPA, for quantitative analysis of gut permeability dynamics...
Changes in microbiome composition are associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet, clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here,...
Background:
IBD is a spectrum of pathologies characterized by dysregulated immune activation leading to uncontrolled response against the intestine, thus resulting in chronic gut inflammation and tissue damage. Due to its complexity, the molecular mechanisms responsible for disease onset and progression are still elusive, thus requiring intense re...
T cells that express the transcription factor RORγ, regulatory (Treg), or conventional (Th17) are strongly influenced by intestinal symbionts. In a genetic approach to identify mechanisms underlying this influence, we performed a screen for microbial genes implicated, in germfree mice monocolonized with Escherichia coli Nissle. The loss of capsule-...
Background: IBD is a spectrum of pathologies characterized by dysregulated immune activation leading to uncontrolled response against intestinal, thus resulting in chronic gut inflammation and tissue damage. Due to its complexity, the molecular mechanisms responsible for disease onset and progression are still elusive, thus requiring intense resear...
Constant exposure to diverse microorganisms has accompanied human evolution and continues to shape immunological development throughout life. In mucosal tissues, both innate and adaptive arms of the immune system are required to support healthy mutualistic interactions with the resident microbiota, while aggressively fighting pathogenic infections....
Changes in microbiome composition have been associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. H...
Inflammatory bowel disease (IBD) is a complex, chronic, and dysregulated inflammatory condition which etiology is still largely unknown. Its prognosis and disease progression are highly variable and unpredictable. IBD comprises several heterogeneous inflammatory conditions ranging from Ulcerative Colitis (UC) to Crohn’s Disease (CD). Importantly, a...
Celiac disease (CD) is a complex immune-mediated chronic disease characterized by a consistent inflammation of the gastrointestinal tract induced by gluten intake in genetically predisposed individuals. Although initiated by the interaction between digestion-derived gliadin, a gluten component, peptides, and the intestinal epithelium, the disorder...
Background & Aims
The intestinal barrier protects intestinal cells from microbes and antigens in the lumen—breaches can alter the composition of the intestinal microbiota, the enteric immune system, and metabolism. We performed a screen to identify molecules that disrupt and support the intestinal epithelial barrier and tested their effects in mice...
The protein translocated intimin receptor (Tir) from enteropathogenic Escherichia coli shares sequence similarity with the host cellular immunoreceptor tyrosine-based inhibition motifs (ITIMs). The ITIMs of Tir are required for Tir-mediated immune inhibition and evasion of host immune responses. However, the underlying molecular mechanism by which...
Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particul...
Over the past decade, our understanding of intestinal immunology has been transformed by the realization that the gut microbiota shapes immune development, function and disease susceptibility. Strikingly, the enteric nervous system is now emerging as a cellular hub that sense microbiota-derived signals and rapidly orchestrate immunological outcomes...
Investigation of host-environment interactions in the gut would benefit from a culture system that maintained tissue architecture yet allowed tight experimental control. We devised a microfabricated organ culture system that viably preserves the normal multicellular composition of the mouse intestine, with luminal flow to control perturbations (e.g...
Citations
... Recently, the effect of the low-FODMAP diet has been examined on a gut organ culture system (developed by Bootz-Maoz et al [59]). Gut-organ cultures were colonized with longitudinal microbiota samples collected from newly diagnosed and therapy-naïve IBS patients receiving a standard 6 wk low FODMAP diet. ...
... https://eu.idtdna.com/Primerquest/Home/Index), and sequences reported below [59]. Small interfering RNA (siRNA) siE2F1, siFSP1, and non-targeting scramble (siCTRL, used as negative control) siRNA oligoribonucleotides were obtained from Merck. ...
... lacks the surface molecules that are normally recognised by the host and therefore identified as a "friendly" bacterium, the host responds by its sequestration in luminal casts as a potentially harmful microbe to avoid dysregulated T cell activation (Sassone-Corsi et al., 2022). ...
... synthesizing specific vitamins and amino acids, including B vitamins and folic acid. Also, these organisms can break down complex carbohydrates such as fiber and starch and act as a protective factor against pathogens [99][100][101]. The research has determined that various factors influence the human microbiota population, such as lifestyle, drugs, diet, environmental conditions, and living with animals [16,102]. ...
... In a set of proof-of-principle experiments, we measured gut permeability ex vivo in response to luminal introduction of EGTA, a calcium chelator that disrupts TJ integrity and paracellular barrier functions (confirmed using dynamic TEER assay (Fig. 1B, C) and ZO-1 staining (Fig. S1A) in Caco-2 monolayers). Colon tissues were dissected from 14d-old mice reared under specific-pathogen-free (SPF) conditions, and connected to the gut culture device as previously described (six tissues per device; Fig. 1A) 7,8,13 . Culture medium containing FITC-dextran (4 kDa) was infused directly into the cultured colons' lumens either with or without EGTA (25 mM). ...
... Gut inflammation is a feature shared by several human diseases specifically affecting the gastrointestinal tract, such as celiac disease [1], cystic fibrosis [2] and inflammatory bowel disease [3]. However, mounting evidence points to the role of inflammation in the pathogenesis of other human diseases, which apparently do not directly involve the gut, such as Parkinson's disease [4] and type 2 diabetes [5]. ...
... In this case, the media described above and an adequate gas supply are also necessary for the tissue to survive. Although the method is not widespread because of its difficulty, it shows reproducible results because several samples are tested under the same conditions [71]. ...
... The tight junctions (TJs) between adjacent epithelial cells are critical components of the intestinal barrier, sealing the paracellular space. ZO-1, Occludin, and Claudin are among the primary constituents of the TJ structure (Grosheva et al., 2020;Mehandru and Colombel, 2021). In the present study, we found that the mRNA expression levels of ZO-1 and Occludin were substantially reduced in the 3.75 mg/kg and 7.5 mg/kg TPT exposure groups, accompanied by a significant decrease in the protein expression of ZO-1 and Occludin. ...
... Using heterologous systems, the recruitment of the adaptor protein beta-arrestin-1 has been described as an essential step for D1R/D3R heteromer to activate Erk1/2 [18]. We also found that D1R-D3R heteromer activation of the G-dependent/Erk1/2 cascade also requires Shp-2; interestingly, the requirement of beta-arrestin in the recruitment of Shp-1 and Shp-2 tyrosine phosphatases to their target receptors has been demonstrated [45][46][47]. Here, we analyzed the role of beta-arrestin1 and beta-arrestin2 in D1R/D3R heteromerinduced signaling using primary cultures of striatal neurons and the siRNA approach. ...
... Some studies have shown that propionic acid is negatively correlated with score on the Unified Parkinson's Disease Rating Scale part III [17], suggesting that propionic acid may be beneficial in PD. Studies have documented numerous advantages of propionate for physiological processes; for example, it attenuates the lipopolysaccharide-induced epithelial-mesenchymal transition [34], encourages intestinal gluconeogenesis [35], modifies the progression of multiple sclerosis by reversing Treg cell/Th17 cell induction, and improves Treg cell function [36]. Propionate can easily cross the blood-brain barrier; in fact, GC studies have shown a high concentration of propionate in the hippocampus [37]. ...