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Review
. 2020 Aug 25:11:1823.
doi: 10.3389/fimmu.2020.01823. eCollection 2020.

Psychological Stress, Intestinal Barrier Dysfunctions, and Autoimmune Disorders: An Overview

Hanna Ilchmann-Diounou  1 , Sandrine Menard  1
Affiliations
Review

Psychological Stress, Intestinal Barrier Dysfunctions, and Autoimmune Disorders: An Overview

Hanna Ilchmann-Diounou et al. Front Immunol. .

Abstract

Autoimmune disorders (ADs) are multifactorial diseases involving, genetic, epigenetic, and environmental factors characterized by an inappropriate immune response toward self-antigens. In the past decades, there has been a continuous rise in the incidence of ADs, which cannot be explained by genetic factors alone. Influence of psychological stress on the development or the course of autoimmune disorders has been discussed for a long time. Indeed, based on epidemiological studies, stress has been suggested to precede AD occurrence and to exacerbate symptoms. Furthermore, compiling data showed that most of ADs are associated with gastrointestinal symptoms, that is, microbiota dysbiosis, intestinal hyperpermeability, and intestinal inflammation. Interestingly, social stress (acute or chronic, in adult or in neonate) is a well-described intestinal disrupting factor. Taken together, those observations question a potential role of stress-induced defect of the intestinal barrier in the onset and/or the course of ADs. In this review, we aim to present evidences supporting the hypothesis for a role of stress-induced intestinal barrier disruption in the onset and/or the course of ADs. We will mainly focus on autoimmune type 1 diabetes, multiple sclerosis and systemic lupus erythematosus, ADs for which we could find sufficient circumstantial data to support this hypothesis. We excluded gastrointestinal (GI) ADs like coeliac disease to privilege ADs not focused on intestinal disorders to avoid confounding factors. Indeed, GIADs are characterized by antibodies directed against intestinal barrier actors.

Keywords: immune response; intestinal permeability; microbiota; multiple sclerosis; psychological stress; systemic lupus erythematosus; type 1 diabetes.

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Figures

Figure 1
Figure 1
Consequences of stress on intestinal barrier and systemic inflammation. Psychological stress can impair intestinal barrier at different levels. Indeed, stress can lead to microbiota dysbiosis, intestinal hyperpermeability, and intestinal inflammation. Interestingly, all these elements are highly connected and regulate one another. Microbiota dysbiosis can trigger intestinal hyperpermeability and intestinal inflammation; and in contrast, both intestinal hyperpermeability and intestinal inflammation can induce microbiota dysbiosis. Finally, stress can also induce systemic inflammation that might be related to intestinal inflammation.
Figure 2
Figure 2
Defect of intestinal barrier and systemic immune response is observed in three examples of autoimmune disorders (ADs): type 1 diabetes (T1D), systemic lupus erythematosus (SLE), and multiple sclerosis (MS). (A) T1D is associated with microbiota dysbiosis, intestinal hyperpermeability, increased IL-17 secretion in the intestine and at systemic level, and increased myeloperoxidase (MPO) in the intestine. Interestingly, colonization by a complex microbiota is protective from type 1 diabetes. (B) SLE is associated with microbiota dysbiosis and increased secretion at the intestinal level of IL-17 and IL-22 by T cells and IFN-α and IFN-β by dendritic cells. At the systemic level, there is a higher secretion of IL-6 and TNF-α by monocytes and macrophages in SLE. Interestingly, colonization by a complex microbiota is deleterious for SLE onset. (C) MS is associated with microbiota dysbiosis, intestinal hyperpermeability, and increased secretion at the intestinal level of IL-17 and IFN-γ by T cells. At the systemic level, the number of innate lymphoid cell (ILC) population was observed in MS. Interestingly, colonization by a complex microbiota is deleterious for MS onset.
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