scholarly journals Therapeutic immunoglobulin A antibody for dysbiosis-related diseases

2021 ◽  
Author(s):  
Reiko Shinkura
Keyword(s):  
Colorectal Cancer ◽  
Pathogenic Bacteria ◽  
Immunoglobulin A ◽  
Microbial Composition ◽  
Protective Function ◽  
Commensal Microbiota ◽  
Pathogenic Escherichia Coli ◽  
Iga Antibodies ◽  
Intestinal Pathogens ◽  
Inflammatory Bowel

Abstract Dysbiosis is alterations in the microbial composition compared with a healthy microbiota and often features a reduction in gut microbial diversity and a change in microbial taxa. Dysbiosis, especially in the gut, has also been proposed to play a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, obesity, diabetes and multiple sclerosis. A body of evidence has shown that intestinal polymeric immunoglobulin A (IgA) antibodies are important to regulate the gut microbiota as well as to exclude pathogenic bacteria or viral infection such as influenza and SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at mucosal sites. Since the 1970s, trials for oral administration of therapeutic IgA or IgG have been performed mainly to treat infectious enteritis caused by pathogenic Escherichia coli or Clostridium difficile. However, few of them have been successfully developed for clinical application up to now. In addition to the protective function against intestinal pathogens, IgA is well known to modulate the gut commensal microbiota leading to symbiosis. Nevertheless, the development of therapeutic IgA drugs to treat dysbiosis is not progressing. In this review, the advantages of therapeutic IgA antibodies and the problems for their development will be discussed.

Selective enrichment of commensal gut bacteria protects againstCitrobacter rodentium-induced colitis

2015 ◽  
Vol 309 (3) ◽  
pp. G181-G192 ◽  
Author(s):  
Linda Vong ◽  
Lee J. Pinnell ◽  
Pekka Määttänen ◽  
C. William Yeung ◽  
Eberhard Lurz ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Intestinal Barrier ◽  
Gut Bacteria ◽  
Enterohemorrhagic Escherichia Coli ◽  
Host Immune System ◽  
Citrobacter Rodentium ◽  
Bacterial Strains ◽  
Microbial Composition ◽  
Selective Enrichment ◽  
Intestinal Pathogens

The intestinal microbiota plays a key role in shaping the host immune system. Perturbation of gut microbial composition, termed dysbiosis, is associated with an increased susceptibility to intestinal pathogens and is a hallmark of a number of inflammatory, metabolic, and infectious diseases. The prospect of mining the commensal gut microbiota for bacterial strains that can impact immune function represents an attractive strategy to counteract dysbiosis and resulting disease. In this study, we show that selective enrichment of commensal gut lactobacilli protects against the murine pathogen Citrobacter rodentium, a well-characterized model of enteropathogenic and enterohemorrhagic Escherichia coli infection. The lactobacilli-enriched bacterial culture prevented the expansion of Gammaproteobacteria and Actinobacteria and was associated with improved indexes of epithelial barrier function (dextran flux), transmissible crypt hyperplasia, and tissue inflammatory cytokine levels. Moreover, cultivation of gut bacteria from Citrobacter rodentium-infected mice reveals the differential capacity of bacterial subsets to mobilize neutrophil oxidative burst and initiate the formation of weblike neutrophil extracellular traps. Our findings highlight the beneficial effects of a lactobacilli -enriched commensal gut microenvironment and, in the context of an intestinal barrier breach, the ability of neutrophils to immobilize both commensal and pathogenic bacteria.

scholarly journals Carotenoid supplementation and retinoic acid in immunoglobulin A regulation of the gut microbiota dysbiosis

2018 ◽  
Vol 243 (7) ◽  
pp. 613-620 ◽  
Author(s):  
Yi Lyu ◽  
Lei Wu ◽  
Fang Wang ◽  
Xinchun Shen ◽  
Dingbo Lin
Keyword(s):  
Retinoic Acid ◽  
Immune System ◽  
Gut Microbiota ◽  
Pathogenic Bacteria ◽  
Immunoglobulin A ◽  
Gut Health ◽  
Commensal Microbiota ◽  
Gut Immune System ◽  
Underlying Mechanisms ◽  
Gut Microbiota Dysbiosis

Dysbiosis, a broad spectrum of imbalance of the gut microbiota, may progress to microbiota dysfunction. Dysbiosis is linked to some human diseases, such as inflammation-related disorders and metabolic syndromes. However, the underlying mechanisms of the pathogenesis of dysbiosis remain elusive. Recent findings suggest that the microbiome and gut immune responses, like immunoglobulin A production, play critical roles in the gut homeostasis and function, and the progression of dysbiosis. In the past two decades, much progress has been made in better understanding of production of immunoglobulin A and its association with commensal microbiota. The present minireview summarizes the recent findings in the gut microbiota dysbiosis and dysfunction of immunoglobulin A induced by the imbalance of pathogenic bacteria and commensal microbiota. We also propose the potentials of dietary carotenoids, such as β-carotene and astaxanthin, in the improvement of the gut immune system maturation and immunoglobulin A production, and the consequent promotion of the gut health. Impact statement The concept of carotenoid metabolism in the gut health has not been well established in the literature. Here, we review and discuss the roles of retinoic acid and carotenoids, including pro-vitamin A carotenoids and xanthophylls in the maturation of the gut immune system and IgA production. This is the first review article about the carotenoid supplements and the metabolites in the regulation of the gut microbiome. We hope this review would provide a new direction for the management of the gut microbiota dysbiosis by application of bioactive carotenoids and the metabolites.

scholarly journals Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota

Science ◽  
2012 ◽  
Vol 338 (6103) ◽  
pp. 120-123 ◽  
Author(s):  
Janelle C. Arthur ◽  
Ernesto Perez-Chanona ◽  
Marcus Mühlbauer ◽  
Sarah Tomkovich ◽  
Joshua M. Uronis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Throughput Sequencing ◽  
Polyketide Synthase ◽  
Invasive Carcinoma ◽  
Intestinal Inflammation ◽  
Interleukin 10 ◽  
Microbial Composition ◽  
Tumor Multiplicity ◽  
E Coli ◽  
Inflammatory Bowel

Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10–deficient (Il10−/−) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)–treated Il10−/− mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10−/− mice, without altering intestinal inflammation. Mucosa-associated pks+E. coli were found in a significantly high percentage of inflammatory bowel disease and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.

scholarly journals The Wanderings of Gut-Derived IgA Plasma Cells: Impact on Systemic Immune Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Selina J. Keppler ◽  
Marie Christine Goess ◽  
Julia M. Heinze
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
B Cell ◽  
Protective Immunity ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Commensal Microbiota ◽  
Mucosal Tissues ◽  
Iga Antibodies ◽  
Antibody Secreting Cells

Humoral immunity is mainly mediated by a B cell population highly specialized to synthesize and secrete large quantities of antibodies – the antibody-secreting cells (ASC). In the gastrointestinal environment, a mixture of foreign antigens from the diet, commensal microbiota as well as occasional harmful pathogens lead to a constant differentiation of B cells into ASC. Due to this permanent immune response, more than 80% of mammalian ASC reside in the gut, of which most express immunoglobulin A (IgA). IgA antibodies contribute to intestinal homeostasis and can mediate protective immunity. Recent evidence points at a role for gut-derived ASC in modulating immune responses also outside of mucosal tissues. We here summarize recent evidence for wandering ASC, their antibodies and their involvement in systemic immune responses.

Periodontopathogens: a new view. Systematic review. Part 2

2020 ◽  
Vol 20 (2) ◽  
pp. 160-167
Author(s):  
E. S. Slazhneva ◽  
E. A. Tikhomirova ◽  
V. G. Atrushkevich
Keyword(s):  
Systematic Review ◽  
Periodontal Disease ◽  
Pathogenic Bacteria ◽  
Periodontal Diseases ◽  
Oral Microbiome ◽  
Controlled Trials ◽  
New Paradigm ◽  
Microbial Composition ◽  
Randomized Controlled ◽  
The Past

Relevance. The modern view of periodontitis as a dysbiotic disease that occurs as a result of changes in the microbial composition of the subgingival region is considered in a systematic review.Purpose. To study a new paradigm of development of generalized periodontitis.Materials and methods. Randomized controlled trials (RCTS) were selected for the study, including cluster RCTS, controlled (non-randomized) microbiological and clinical studies of the oral microbiome in adult patients with generalized periodontitis over the past 10 years.Results. The transition from a symbiotic microflora to a dysbiotic pathogenic community triggers the host's inflammatory response, which contributes to the development of periodontal diseases. Modern ideas about periodontal pathogenic bacteria dictate new requirements for the treatment of periodontal diseases. The second part of the review examines the microbial profiles of periodontal disease in various nosological forms, the mechanisms of the immune response and approaches to the treatment of periodontal disease from the perspective of biofilm infection.Conclusions. As follows from modern literature periodontitis is to a certain extent caused by the transition from a harmonious symbiotic bacterial community to a dysbiotic one. Recent scientific studies have shown that not single microorganism is not able to cause disease but the microbial community as a whole leads to the development of pathology.

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

2019 ◽  
Vol 18 (31) ◽  
pp. 2731-2740 ◽  
Author(s):  
Sandeep Tiwari ◽  
Debmalya Barh ◽  
M. Imchen ◽  
Eswar Rao ◽  
Ranjith K. Kumavath ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
In Vitro Study ◽  
Docking Studies ◽  
Acetate Kinase ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

scholarly journals Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Postoperative Complications ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Tumor Resection ◽  
Microbial Composition ◽  
Colorectal Cancer Surgery ◽  
Long Term Changes ◽  
Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

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