Intestinal dysbiosis in inflammatory bowel disease associated with primary immunodeficiency

Sokol, Harry; Mahlaoui, Nizar; Aguilar, Claire; Bach, Perrine; Join‐Lambert, Olivier; Garraffo, Aurélie; Seksik, Philippe; Danion, François; Jégou, Sarah; Straube, Marjolène; Lenoir, Christelle; Neven, Bénédicte; Moshous, Despina; Blanche, Stéphane; Pigneur, Bénédicte; Goulet, Olivier; Ruemmele, Frank; Suarez, Félipe; Beaugerie, Laurent; Pannier, Stéphanie; Mazingue, Françoise; Lortholary, Olivier; Galicier, Lionel; Pïcard, Capucine; Basile, Geneviève de Saint; Latour, Sylvain; Fischer, Alain

doi:10.1016/j.jaci.2018.09.021

Cited by 24 publications

(24 citation statements)

References 14 publications

(12 reference statements)

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“…Beside pathogens which are typically acquired from the environment, often provoking acute infections and are the target of immunity, also members of the resident microbiota, found in most healthy hosts, may be the cause for several inflammatory disorders in a genetic or environmental predisposed organism (90)(91)(92)(93)(94). The exact mechanisms mediating pathology remain largely unclear, but commensal bacteria are capable of triggering inflammatory disease in immunosufficient rodents by altering barrier function, invading the gut epithelium and stimulating local inflammatory responses (pathobionts) (93,94).…”

Section: Discussionmentioning

confidence: 99%

Bacterial Immunogenicity Is Critical for the Induction of Regulatory B Cells in Suppressing Inflammatory Immune Responses

et al. 2020

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B cells fulfill multifaceted functions that influence immune responses during health and disease. In autoimmune diseases, such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, depletion of functional B cells results in an aggravation of disease in humans and respective mouse models. This could be due to a lack of a pivotal B cell subpopulation: regulatory B cells (Bregs). Although Bregs represent only a small proportion of all immune cells, they exhibit critical properties in regulating immune responses, thus contributing to the maintenance of immune homeostasis in healthy individuals. In this study, we report that the induction of Bregs is differentially triggered by the immunogenicity of the host microbiota. In comparative experiments with low immunogenic Bacteroides vulgatus and strong immunogenic Escherichia coli, we found that the induction and longevity of Bregs depend on strong Toll-like receptor activation mediated by antigens of strong immunogenic commensals. The potent B cell stimulation via E. coli led to a pronounced expression of suppressive molecules on the B cell surface and an increased production of anti-inflammatory cytokines like interleukin-10. These bacteria-primed Bregs were capable of efficiently inhibiting the maturation and function of dendritic cells (DCs), preventing the proliferation and polarization of T helper (Th)1 and Th17 cells while simultaneously promoting Th2 cell differentiation in vitro. In addition, Bregs facilitated the development of regulatory T cells (Tregs) resulting in a possible feedback cooperation to establish immune homeostasis. Moreover, the colonization of germfree wild type mice with E. coli but not B. vulgatus significantly reduced intestinal inflammatory processes in dextran sulfate sodium (DSS)-induced colitis associated with an increase induction of immune suppressive Bregs. The quantity of Bregs directly correlated with the severity of inflammation. These findings may provide new insights and therapeutic approaches for B cell-controlled treatments of microbiota-driven autoimmune disease.

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Section: Discussionmentioning

confidence: 99%

Bacterial Immunogenicity Is Critical for the Induction of Regulatory B Cells in Suppressing Inflammatory Immune Responses

et al. 2020

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“…This association of immunosuppressive phenomena with bacterial dysbiosis in cancer has also been supported by the detection of dysbiotic intestinal microbiota in patients with primary immunodeficiency, such as X-linked inhibitor of apoptosis (XIAP) deficiency. Interestingly, not only do the intestinal microbiota present alterations in its composition in these patients, but also some of the taxa with increased abundance ( Scardovia , Fusobacterium , Rothia dentocariosa , and Veillonella ) are members of the oral microbiota [182] that are also involved in the pathogenesis of inflammatory bowel disease and CRC [183]. Thus, the intestinal microbiota of patients with primary immunodeficiency presents distinct perturbations, indicating a primary defect in host immunity as a core of intestinal dysbiosis.…”

Section: Possible Mechanisms Of Oral Microbiota Involvement In Crcmentioning

confidence: 99%

Oral Bacteria and Intestinal Dysbiosis in Colorectal Cancer

Koliarakis

Messaritakis

Νikolouzakis

et al. 2019

IJMS

156

148

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The human organism coexists with its microbiota in a symbiotic relationship. These polymicrobial communities are involved in many crucial functions, such as immunity, protection against pathogens, and metabolism of dietary compounds, thus maintaining homeostasis. The oral cavity and the colon, although distant anatomic regions, are both highly colonized by distinct microbiotas. However, studies indicate that oral bacteria are able to disseminate into the colon. This is mostly evident in conditions such as periodontitis, where specific bacteria, namely Fusobacterium nucrelatum and Porphyromonas gingivalis project a pathogenic profile. In the colon these bacteria can alter the composition of the residual microbiota, in the context of complex biofilms, resulting in intestinal dysbiosis. This orally-driven disruption promotes aberrant immune and inflammatory responses, eventually leading to colorectal cancer (CRC) tumorigenesis. Understanding the exact mechanisms of these interactions will yield future opportunities regarding prevention and treatment of CRC.

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“…Few other studies evaluated the gut microbiota-host interactions in other human IEI. Fecal microbiota and association with IBD were analyzed in patients with chronic granulomatous disease (CGD, 10 patients), X-linked inhibitor of apoptosis (XIAP) deficiency (six patients) and partial tetratricopeptide repeat domain 7A (TTC7A) deficiency (five patients), and compared to non-genetically-determined/polygenic IBD (18 patients) and 23 healthy subjects [134]. CGD is caused by gene mutations that affect the function of the nicotinamide adenine dinucleotide phosphate (NADPH) complex, resulting in defective production of microbicidal reactive oxygen species (ROS) [135,136].…”

Section: Studies In Other Human Inborn Errors Of Immunitymentioning

confidence: 99%

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

Castagnoli

Pala

Bosticardo

et al. 2021

IJMS

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Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host’s innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.

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Intestinal dysbiosis in inflammatory bowel disease associated with primary immunodeficiency

Cited by 24 publications

References 14 publications

Bacterial Immunogenicity Is Critical for the Induction of Regulatory B Cells in Suppressing Inflammatory Immune Responses

Bacterial Immunogenicity Is Critical for the Induction of Regulatory B Cells in Suppressing Inflammatory Immune Responses

Oral Bacteria and Intestinal Dysbiosis in Colorectal Cancer

Gut Microbiota–Host Interactions in Inborn Errors of Immunity

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