GUT-the Trojan Horse in Remote Organs’ Autoimmunity

Abstract

Human beings assemble and maintain a diverse but host-specific gut microbial community along the longitudinal axis of the intestines. Helped by a functional tight junction, the default response to commensal microbes is tolerance, whereas the default response to pathogens is an intricately orchestrated immune response, resulting in pathogen clearance. Nutrients and industrial food additives were suggested to impact the intestinal ecosystem and to breach tight junction integrity. Taken together, certain nutritional components, increased intestinal permeability, disease specific dysbiotic pathobionts and their capacity of post translation modification of proteins, are luminal events that impact autoimmunogenesis. The present review expands on the multi gut originated axes and their relationship to remote organ autoimmune diseases. Brain, joint, bone, endocrine, liver, kidney, heart, lung and skin autoimmune diseases are connected to the intestinal luminal compartmental deregulated events to form the gut-systemic organs axes.

Gut-thyroid axis and celiac disease

“…This process is in fact at the basis of the progression of autoimmune diseases and is called molecular mimicry. In the gut, inflammatory pathologies that are related to dysbiosis associated with various factors, such as genetic factors and food, cause alterations of the immune system characterized in IBD and CD (9, 10, 14). Those enteric eco-events induce systemic inflammatory responses, leading to the systemic manifestations of IBD and/or CD, affecting remote organs including the thyroid (10, 14).…”

“…In dysbiotic conditions, this balance is compromised and results in abnormal interaction between the host and microbiota (10). In contrast, the place of the altered microbiome, mainly decrease diversity, in autoimmunity induction was well described (9, 10, 14). Adding the substantial involvement of the microbiome in IBD and CD development and the potential place in HT evolvement, dysbiosis is suggested as a major player in intestinal and thyroidal autoimmunity interaction (12, 13).…”

“…Several potential mechanisms were suggested for the gut mucosa and luminal ecosystems involvement in the thyroid autoimmunity: (i) Gut dysbiosis might disturb the finely tuned immune balance and break tolerance to self-antigens and non-pathogenic non-self-antigens, by posttranslational modification proteins, inducing autoimmunity; (ii) association of lipopolysaccharide-induced Toll-like receptor (TLR) activation with thyroiditis development or production of anti-thyroglobulin antibody in mice was suggested; (iii) induction of Th1 to Th2 shift, inhibition of Th17 differentiation and oral tolerance induction, by retinoic acid might activate tolerogenic immune responses in the gut; (iv) breaching tight junction integrity, resulting in the leaky gut barrier is a common shared pathway in autoimmunogenesis; (v) not less important is the transcriptomic, proteinomic and the metabolomics changes induced by the gut microbes, being direct messengers between the bugs and us. Changes in microbiota and short chain fatty acids production are clearly related to the pathogenesis of CD, but their role in thyroid autoimmunity induction or protection remains to be investigated (9, 10, 12, 13, 14, 15, 16). …”

“…Finally, the plasma concentration of tryptophan is dependent on microbiome composition. Being an essential amino acid and precursor of serotonin, tryptophan impact enteric neurotransmitters balance (14). …”

“…In the opposite aspect, the endogenous hormones can modulate the bacterial proliferative capacity and pathogenicity. Dopamine, norepinephrine, nitric oxide and the inhibitory transmitter GABA are molecules originated from the luminal microbes that influence our endogenous endocrine network (referred to as ‘Microbial endocrinology’ (14)). The microbial intestinal-thyroiditis interrelations were not described in CD and IBD.…”