Interaction of Intestinal Microorganisms with the Human Host in the Framework of Autoimmune Diseases

Abstract

Autoimmune diseases, such as systemic lupus erythematosus (SLE), are caused by a complex interaction of environmental-, genetic-, and sex-related factors. Although SLE has traditionally been considered independent from the microbiota, recent work published during the last 5 years suggests a strong connection between SLE and the composition of our gut commensals as one of the main environmental factors linked to this disease. Preliminary data have evidenced that (i) interaction of certain microbial-derived molecules with specific cell receptors and (ii) the influence of certain commensal microorganisms over specific immune cell subsets plays an important role in the pathogenesis of SLE and SLE-like diseases. In addition, epigenetic changes driven by certain microbial groups have been recently proposed as an additional link between gut microbiota and SLE. As immune responses elicited against commensal bacteria are deeply dependent on the composition of the latter, and as microbial populations can be modified by dietary interventions, identifying the precise gut microorganisms responsible for worsening the SLE symptoms is of crucial importance for this and other SLE-related diseases, including antiphospholipid syndrome or lupus nephritis. In this minireview, the current knowledge on the relationships between microbes and SLE and SLE-related diseases is compiled and discussed.

Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis

“…Bacterial components may act as antigens that stimulate the systemic immune response[30,31,34,47,48] or that prime immune cells within the intestine that subsequently access peripheral lymphoid tissue[39,117,118]. Molecular mimicry between microbial and host-derived antigens and promiscuous targeting by antigen-sensitized lymphocytes may then initiate or strengthen the autoreactive response in genetically-predisposed individuals[33,57,115]. Investigations in cell cultures, animal models, and patients with diverse systemic immune-mediated diseases have justified these hypotheses and warranted their consideration in autoimmune hepatitis[46-48].…”

“…Epitopes can be shared between microbial components and self-antigens, and this molecular mimicry can result in cross-reacting antibodies or the activation of T lymphocytes in genetically-predisposed individuals[33,184,185] (Figure 2). The reactive T lymphocytes can in turn exhibit promiscuous activity[186] and target epitopes that are distant homologues to the initial antigenic trigger (epitope spread)[187] (Table 1).…”

GUT-the Trojan Horse in Remote Organs’ Autoimmunity

“…Recent studies show that the complex communities of commensal species that occupy our mucosal tissues influence not only the development and homeostasis of the host's immune system but also confer susceptibility to immunemediated disease. Alterations in the fine-tuned but fragile microbiome-host relationship can result in community inhabitant change, whereby the dysbiota is overriding the microbiota, setting the stage for immune dysregulation and potential autoimmunogenesis [13][14][15]. Multiple animal models of human ADs suggest a direct involvement of the commensal microbiota, when invaded with the pathogenic dysbiota, in disease development.…”

“…Data is accumulating that intestinal luminal environmental factors might perturbate the regulatory mechanisms of the tight junction, resulting in a leaky gut thus breaking equilibrium between tolerance and immunity to nonself-antigens. Nutrients, toxins, allergens, carcinogens, intestinal infections, dysbiotic bacteria, drugs and stress and the recently described industrial processed food additives, can breach the tight junction integrity [3,4,[7][8][9][10]12,13,[15][16][17][18]23,24,28,29]. In fact, TJ dysfunction seems to be a primary defect in AD [28][29][30].…”

Microbiota and oxidant-antioxidant balance in systemic lupus erythematosus

“…Although the cause of this pathology is unknown, accumulating evidence suggests that its development is conditioned by genetic, hormonal and environmental factors (7,8), including gut microbiota. Strong evidence in the last years suggests a connection between lupus and the composition of our gut commensals (9). Microbiota might have different mechanisms of action over the host balancing anti-and pro-inflammatory responses (10).…”