scholarly journals Analyzing the Role of Gut Microbiota on the Onset of Autoimmune Diseases Using TNFΔARE Murine Model

2021 ◽  
Vol 10 (1) ◽  
pp. 73
Author(s):  
Vivienne Edwards ◽  
Dylan L. Smith ◽  
Francoise Meylan ◽  
Linda Tiffany ◽  
Sarah Poncet ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Disease Transmission ◽  
Bioinformatics Analysis ◽  
Inflammatory Diseases ◽  
Anaerobic Conditions ◽  
Fecal Matter ◽  
Rrna Sequencing ◽  
Inflammatory Bowel ◽  
Transmission Status

Very little is known about disease transmission via the gut microbiome. We hypothesized that certain inflammatory features could be transmitted via the gut microbiome and tested this hypothesis using an animal model of inflammatory diseases. Twelve-week-old healthy C57 Bl/6 and Germ-Free (GF) female and male mice were fecal matter transplanted (FMT) under anaerobic conditions with TNFΔARE−/+ donors exhibiting spontaneous Rheumatoid Arthritis (RA) and Inflammatory Bowel Disease (IBD) or with conventional healthy mice control donors. The gut microbiome analysis was performed using 16S rRNA sequencing amplification and bioinformatics analysis with the HIVE bioinformatics platform. Histology, immunohistochemistry, ELISA Multiplex analysis, and flow cytometry were conducted to confirm the inflammatory transmission status. We observed RA and IBD features transmitted in the GF mice cohort, with gut tissue disruption, cartilage alteration, elevated inflammatory mediators in the tissues, activation of CD4/CD8+ T cells, and colonization and transmission of the gut microbiome similar to the donors’ profile. We did not observe a change or transmission when conventional healthy mice were FMT with TNFΔARE−/+ donors, suggesting that a healthy microbiome might withstand an unhealthy transplant. These findings show the potential involvement of the gut microbiome in inflammatory diseases. We identified a cluster of bacteria playing a role in this mechanism.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

Infection and spondyloarthritis

2016 ◽  
Author(s):  
Marjatta Leirisalo-Repo ◽  
John D. Carter
Keyword(s):  
Inflammatory Bowel Disease ◽  
Inflammatory Diseases ◽  
Strong Association ◽  
Hla B27 ◽  
Contributing Factors ◽  
Juvenile Onset ◽  
Psoriasis Arthritis ◽  
Family Aggregation ◽  
Inflammatory Bowel

Spondyloarthritis (SpA) is the designation encompassing a group of inflammatory diseases with several features in common. The patients have mono- or oligoarthritis with or without inflammatory back symptoms. Distinctive extra-articular inflammatory symptoms also characterize the diseases. The diagnostic subgroups in the SpA family include reactive arthritis (ReA), ankylosing spondylitis (AS), arthritis associated with inflammatory bowel disease (IBD), psoriasis arthritis (PsA), and some forms of juvenile-onset arthritis. These diseases share a strong association with a genetic marker, HLA-B27, absence of rheumatoid factor, tendency to family aggregation, and frequently occurring extra-articular manifestations. This chapter discusses the role of infections, either as triggering of the disease, most evident in the case of ReA, or as possibly contributing factors in the development of chronic forms of SpA and AS.

scholarly journals Selective Tyrosine Kinase 2 Inhibition for Treatment of Inflammatory Bowel Disease: New Hope on the Rise

2021 ◽  
Author(s):  
Silvio Danese ◽  
Laurent Peyrin-Biroulet
Keyword(s):  
Inflammatory Bowel Disease ◽  
Tyrosine Kinase ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Janus Kinase ◽  
Type I ◽  
Tyrosine Kinase 2 ◽  
Immune Mediated ◽  
Inflammatory Bowel

Abstract Conventional systemic and biologic agents are the mainstay of inflammatory bowel disease (IBD) management; however, many of these agents are associated with loss of clinical response, highlighting the need for effective, novel targeted therapies. Janus kinase (JAK) 1-3 and tyrosine kinase 2 (TYK2) mediate signal transduction events downstream of multiple cytokine receptors that regulate targeted gene transcription, including the interleukin-12, interleukin-23, and type I interferon receptors for TYK2. This review summarizes the role of TYK2 signaling in IBD pathogenesis, the differential selectivity of TYK2 inhibitors, and the potential clinical implications of TYK2 inhibition in IBD. A PubMed literature review was conducted to identify studies of JAK1-3 and TYK2 inhibitors in IBD and other immune-mediated inflammatory diseases. Key efficacy and safety information was extracted and summarized. Pan-JAK inhibitors provide inconsistent efficacy in patients with IBD and are associated with toxicities resulting from a lack of selectivity at therapeutic dosages. Selective inhibition of TYK2 signaling via an allosteric mechanism, with an agent that binds to the regulatory (pseudokinase) domain, may reduce potential toxicities typically associated with JAK1-3 inhibitors. Deucravacitinib, a novel, oral, selective TYK2 inhibitor, and brepocitinib and PF-06826647, TYK2 inhibitors that bind to the active site in the catalytic domain, are in development for IBD and other immune-mediated inflammatory diseases. Allosteric TYK2 inhibition is more selective than JAK1-3 inhibition and has the potential to limit toxicities typically associated with JAK1-3 inhibitors. Future studies will be important in establishing the role of selective, allosteric TYK2 inhibition in the management of IBD.

The therapeutic use of the zonulin inhibitor AT-1001 (Larazotide) for a variety of acute and chronic inflammatory diseases

2021 ◽  
Vol 28 ◽  
Author(s):  
Jacopo Troisi ◽  
Giorgia Venutolo ◽  
Concetta Terracciano ◽  
Matteo Delli Carri ◽  
Simone Di Micco ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Inflammatory Diseases ◽  
Endothelial Permeability ◽  
Careful Examination ◽  
Subsequent Increase ◽  
Inflammatory Bowel

Background: The involvement of intercellular tight junctions and, in particular, the modulation of their competency by the zonulin pathway with a subsequent increase in epithelial and endothelial permeability, has been described in several chronic and acute inflammatory diseases. In this scenario, Larazotide, a zonulin antagonist, could be employed as a viable therapeutic strategy. Objective: The present review aims to describe recent research and current observations about zonulin involvement in several diseases and the use of its inhibitor Larazotide for their treatment. Methods: A systematic search was conducted on PubMed and Google Scholar, resulting in 209 publications obtained with the following search query: “Larazotide,” “Larazotide acetate,” “AT-1001,” “FZI/0” and “INN-202.” After careful examination, some publications were removed from consideration because they were either not in English or were not directly related to Larazotide. Results: The obtained publications were subdivided according to Larazotide’s mechanism of action and different diseases: celiac disease, type 1 diabetes, other autoimmune diseases, inflammatory bowel disease, Kawasaki disease, respiratory (infective and/or non-infective) diseases, and other. Conclusions: A substantial role of zonulin in many chronic and acute inflammatory diseases has been demonstrated in both in vivo and in vitro, indicating the possible efficacy of a Larazotide treatment. Moreover, new possible molecular targets for this molecule have also been demonstrated.

scholarly journals Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

2019 ◽  
Vol 116 (52) ◽  
pp. 26717-26726 ◽  
Author(s):  
Paola Menghini ◽  
Daniele Corridoni ◽  
Ludovica F. Buttó ◽  
Abdullah Osme ◽  
Sushma Shivaswamy ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Intestinal Microbiome ◽  
Lactobacillus Salivarius ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Antiinflammatory Effects

Crohn’s disease and ulcerative colitis are chronic and progressive inflammatory bowel diseases (IBDs) that are attributed to dysregulated interactions between the gut microbiome and the intestinal mucosa-associated immune system. There are limited studies investigating the role of either IL-1α or IL-1β in mouse models of colitis, and no clinical trials blocking either IL-1 have yet to be performed. In the present study, we show that neutralization of IL-1α by a specific monoclonal antibody against murine IL-1α was highly effective in reducing inflammation and damage in SAMP mice, mice that spontaneously develop a Crohn’s-like ileitis. Anti-mouse IL-1α significantly ameliorated the established, chronic ileitis and also protected mice from developing acute DSS-induced colitis. Both were associated with taxonomic divergence of the fecal gut microbiome, which was treatment-specific and not dependent on inflammation. Anti–IL-1α administration led to a decreased ratio ofProteobacteriatoBacteroidetes, decreased presence ofHelicobacterspecies, and elevated representation ofMucispirillum schaedleriandLactobacillus salivarius. Such modification in flora was functionally linked to the antiinflammatory effects of IL-1α neutralization, as blockade of IL-1α was not effective in germfree SAMP mice. Furthermore, preemptive dexamethasone treatment of DSS-challenged SAMP mice led to changes in flora composition without preventing the development of colitis. Thus, neutralization of IL-1α changes specific bacterial species of the intestinal microbiome, which is linked to its antiinflammatory effects. These functional findings may be of significant value for patients with IBD, who may benefit from targeted IL-1α–based therapies.

scholarly journals Interaction between autophagy and the NLRP3 inflammasome

2019 ◽  
Vol 51 (11) ◽  
pp. 1087-1095 ◽  
Author(s):  
Zhenrui Cao ◽  
Yanhao Wang ◽  
Zhimin Long ◽  
Guiqiong He
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Dynamic Balance ◽  
Cell Structure ◽  
Innate Immune ◽  
Interleukin 18 ◽  
Disease Treatment ◽  
Selective Autophagy ◽  
Inflammatory Bowel

Abstract Autophagy, a metabolic pathway that plays an important role in maintaining the dynamic balance of cells, has two types, i.e. non-selective autophagy and selective autophagy. The role of non-selective autophagy is primarily to allow cells to circulate nutrients in an energy-limited environment, while selective autophagy primarily cleans up the organelles inside the cells to maintain the cell structure. The NLRP3 inflammasome is an innate immune response produced by the organism that can promote the secretion of interleukin-1β and interleukin-18 through caspase-1 activation and resist the damage of some pathogens. However, when the NLRP3 inflammasome is overactivated, it can cause various inflammatory diseases, such as inflammatory liver disease and inflammatory bowel disease. Many previous studies have shown that autophagy can inhibit the NLRP3 inflammasome, while in recent years, new studies have found that autophagy can also promote the NLRP3 inflammasome in some cases, and the NLRP3 inflammasome can, in turn, affect autophagy. In this review, the interaction between autophagy and the NLRP3 inflammasome is explored, and then the application of this interaction in disease treatment is discussed.

scholarly journals JAK inhibitors and infections risk: focus on herpes zoster

2020 ◽  
Vol 12 ◽  
pp. 1759720X2093605
Author(s):  
Flavia Sunzini ◽  
Iain McInnes ◽  
Stefan Siebert
Keyword(s):  
Herpes Zoster ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Pathogenic Role ◽  
Immune Mediated ◽  
Post Marketing ◽  
Inflammatory Bowel

Currently, there is a growing interest in Janus kinase (JAK) intracellular signalling since targeted inhibitors against these pathways are proving effective in the treatment of a range of immune-mediated diseases, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease and atopic dermatitis. In particular, post marketing experience and the increasing development of new pharmacological inhibitors of broad and increasingly selective JAK pathways provide new insights into the JAK pathway role in viral infections as well as their pathogenic role in immune-mediated inflammatory diseases. Herein we provide an overview of the biological role of JAK signalling and its role in immunity against viruses, with particular regard to herpes zoster reactivation. Thereafter, we will discuss the evidence currently available on the principal JAK inhibitors and their association with viral infections.

scholarly journals Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Giljae Lee ◽  
Hyun Ju You ◽  
Jasmohan S. Bajaj ◽  
Sae Kyung Joo ◽  
Junsun Yu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
External Validation ◽  
Nonalcoholic Fatty Liver ◽  
Significant Fibrosis ◽  
Representative Species ◽  
Microbiome Diversity ◽  
Rrna Sequencing ◽  
Obese Subjects ◽  
Metagenome Sequencing

Abstract Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.

scholarly journals Faecalibacterium prausnitzii: A Next-Generation Probiotic in Gut Disease Improvement

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiaoya He ◽  
Shuyang Zhao ◽  
Yan Li
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Inflammatory Diseases ◽  
Symbiotic Bacterium ◽  
Fecal Microbiota ◽  
Next Generation ◽  
Faecalibacterium Prausnitzii ◽  
Inflammatory Bowel ◽  
Therapeutic Tools ◽  
Culture Strategy

The researchers are paying more attention to the role of gut commensal bacteria in health development beyond the classical pathogens. It has been widely demonstrated that dysbiosis, which means the alternations of the gut microbial structure, is closely associated with development of intestinal chronic inflammation-related diseases such as inflammatory bowel disease (IBD), and even infectious diseases including bacterial and viral infection. Thus, for reshaping ecological balance, a growing body of the literatures have proposed numerous strategies to modulate the structure of the gut microbiota, which provide more revelation for amelioration of these inflammation or infection-related diseases. While the ameliorative effects of traditional probiotics seem negligeable, emerging next generation probiotics (NGPs) start to receive great attention as new preventive and therapeutic tools. Encouragingly, within the last decade, the intestinal symbiotic bacterium Faecalibacterium prausnitzii has emerged as the “sentinel of the gut,” with multifunction of anti-inflammation, gut barrier enhancement, and butyrate production. A lower abundance of F. prausnitzii has been shown in IBD, Clostridium difficile infection (CDI), and virus infection such as COVID-19. It is reported that intervention with higher richness of F. prausnitzii through dietary modulation, fecal microbiota transplantation, or culture strategy can protect the mice or the subjects from inflammatory diseases. Therefore, F. prausnitzii may have potential ability to reduce microbial translocation and inflammation, preventing occurrences of gastrointestinal comorbidities especially in COVID-19 patients.

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