Microbial drivers of IBD identified by levels of IgA coating

Leake, Isobel

doi:10.1038/nrgastro.2014.166

Cited by 3 publications

(4 citation statements)

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“…These antibodies provide protection against infection by binding to and coating pathogens within the intestinal lumen. Studies completed by our group [27], and others [28, 29] suggest that coating of intestinal bacteria with high-affinity IgA can be used to identify pathogenic strains involved in the development of IBD. A recent study by D’Auria et al supported our hypothesis as they reported a difference in taxa bound by IgA compared to total bacteria in healthy subjects [30].…”

Section: Introductionmentioning

confidence: 99%

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

et al. 2019

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BackgroundInflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis.ResultsIgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not.ConclusionUsing IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0604-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

et al. 2019

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“…Their analysis, despite covering a larger cohort, yielded significant results when IBD patients were combined in a single group and compared with healthy controls. Shapiro et al but also prior studies (Badr‐el‐Din et al , 1988 ; Leake, 2014 ; Viladomiu et al , 2017 ; Lin et al , 2018 ; Sterlin et al , 2020 ) concluded that host immune response to specific microbiota could be added to the combination of genetic susceptibility and environmental factors that are generally associated with IBD immunopathogenesis. Accordingly, we hypothesized that diving deeper into specific subclass‐associated functional and microbial discrepancies in IBD could be very useful.…”

Section: Discussionmentioning

confidence: 98%

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confidence: 82%

Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases

et al. 2022

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Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2‐microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC‐purified IgA, we show that reverse‐transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA‐bound microbiota in CD and UC showed distinct IgA1‐ and IgA2‐associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti‐glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.

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“…Previous methods for pathobiont discovery in IBD patients focused on identifying intestinal bacteria bound to IgA ( 368 , 369 ). Currently, nucleic acids sequencing analysis of IgG-bound microbes is considered a more clinically relevant method ( 370 ), since in IBD patients, the level of IgGs in the gut lumen is elevated ( 371 ), and IgGs seem to be more specific toward pathogens than IgAs ( 372 ).…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

Intestinal Microbiota in Common Chronic Inflammatory Disorders Affecting Children

et al. 2021

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The incidence and prevalence rate of chronic inflammatory disorders is on the rise in the pediatric population. Recent research indicates the crucial role of interactions between the altered intestinal microbiome and the immune system in the pathogenesis of several chronic inflammatory disorders in children, such as inflammatory bowel disease (IBD) and autoimmune diseases, such as type 1 diabetes mellitus (T1DM) and celiac disease (CeD). Here, we review recent knowledge concerning the pathogenic mechanisms underlying these disorders, and summarize the facts suggesting that the initiation and progression of IBD, T1DM, and CeD can be partially attributed to disturbances in the patterns of composition and abundance of the gut microbiota. The standard available therapies for chronic inflammatory disorders in children largely aim to treat symptoms. Although constant efforts are being made to maximize the quality of life for children in the long-term, sustained improvements are still difficult to achieve. Additional challenges are the changing physiology associated with growth and development of children, a population that is particularly susceptible to medication-related adverse effects. In this review, we explore new promising therapeutic approaches aimed at modulation of either gut microbiota or the activity of the immune system to induce a long-lasting remission of chronic inflammatory disorders. Recent preclinical studies and clinical trials have evaluated new approaches, for instance the adoptive transfer of immune cells, with genetically engineered regulatory T cells expressing antigen-specific chimeric antigen receptors. These approaches have revolutionized cancer treatments and have the potential for the protection of high-risk children from developing autoimmune diseases and effective management of inflammatory disorders. The review also focuses on the findings of studies that indicate that the responses to a variety of immunotherapies can be enhanced by strategic manipulation of gut microbiota, thus emphasizing on the importance of proper interaction between the gut microbiota and immune system for sustained health benefits and improvement of the quality of life of pediatric patients.

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Microbial drivers of IBD identified by levels of IgA coating

Cited by 3 publications

References 1 publication

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases

Intestinal Microbiota in Common Chronic Inflammatory Disorders Affecting Children

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