Neuroimmunogastroenterology: At the Interface of Neuroimmunology and Gastroenterology

Sanchez, John Michael S.; McNally, J. Scott; Cortez, Melissa; Hemp, James; Pace, Laura A.; Clardy, Stacey

doi:10.3389/fneur.2020.00787

Cited by 8 publications

(8 citation statements)

References 241 publications

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“…It is thus possible that patients with irAEs harbor commensal-specific T cells that are also cross-reactive to host proteins, with these cross-reactive T cells becoming further dysregulated in response to CPI treatment. Consistent with such a model, gut T cells have previously been shown to contribute to the incidence of CNS inflammation in the context of celiac disease and IBD 57,58 . While celiac disease is caused by the generation of food-reactive T cells and other immune populations, and affected patients experience abdominal pain in the small intestine where food-derived antigens are abundant 59 , a subset of celiac disease patients also exhibit inflammation in the brain 60,61 , presumably due to the migration of dysregulated T cells from the gut to the CNS.…”

Section: Discussionmentioning

confidence: 60%

Commensal-specific CD4 T cells promote inflammation in the central nervous system via molecular mimicry

White

Cabrera

Ochoa-Raya

et al. 2022

Preprint

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Commensal bacteria are critical regulators of both tissue homeostasis and the development and exacerbation of autoimmunity. However, it remains unclear how the intestinal microbiota contributes to inflammation in tissues such as the central nervous system (CNS) where these microbes are typically absent and whether T cell receptor (TCR) specificity for commensal-derived antigens is important to the development of tissue inflammation-related outcomes. Here, we found that ileum- and cecum-colonizing segmented filamentous bacteria (SFB)-specific T cells (clone TCR7B8) can infiltrate the CNS wherein they can be reactivated and produce high levels of inflammatory cytokines including IFNg, IL-17A, TNFa, and GM-CSF in the absence of regulatory T cells. In contrast, other SFB-specific T cells (clone TCR1A2) recognizing an epitope in which 8/9 amino acids overlap with those recognized by TCR7B8 failed to induce such neuroinflammation. Despite their similar SFB-derived peptide antigen targets, TCR7B8 was found to recognize peptides derived from host proteins including receptor tyrosine-protein kinase ErbB2, trophinin 1, and anaphase-promoting complex subunit 2 in vitro, whereas TCR1A2 did not, indicating that TCR7B8 induces CNS inflammation via molecular mimicry. Immune checkpoint blockade accelerated TCR7B8-mediated CNS inflammation, suggesting a potential cause of immune-related adverse events induced in cancer patients undergoing such treatment. Together, our findings reveal a potential mechanism whereby gut commensal-specific T cells are dysregulated and contribute to extraintestinal inflammation.

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Section: Discussionmentioning

confidence: 60%

Commensal-specific CD4 T cells promote inflammation in the central nervous system via molecular mimicry

White

Cabrera

Ochoa-Raya

et al. 2022

Preprint

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“…That a leaky gut could indeed lead to neurologic manifestations is also clearly corroborated by the noted observation that IBD is often associated with CNS demyelination, the hallmark of MS (70,71); conversely, neurological disorders are often associated with gastrointestinal symptoms (72).…”

Section: Neurological Consequences Of a "Leaky" Gutmentioning

confidence: 73%

The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?

Parodi

Rosbo

2021

Front. Immunol.

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A large and expending body of evidence indicates that the gut-brain axis likely plays a crucial role in neurological diseases, including multiple sclerosis (MS). As a whole, the gut-brain axis can be considered as a bi-directional multi-crosstalk pathway that governs the interaction between the gut microbiota and the organism. Perturbation in the commensal microbial population, referred to as dysbiosis, is frequently associated with an increased intestinal permeability, or “leaky gut”, which allows the entrance of exogeneous molecules, in particular bacterial products and metabolites, that can disrupt tissue homeostasis and induce inflammation, promoting both local and systemic immune responses. An altered gut microbiota could therefore have significant repercussions not only on immune responses in the gut but also in distal effector immune sites such as the CNS. Indeed, the dysregulation of this bi-directional communication as a consequence of dysbiosis has been implicated as playing a possible role in the pathogenesis of neurological diseases. In multiple sclerosis (MS), the gut-brain axis is increasingly being considered as playing a crucial role in its pathogenesis, with a major focus on specific gut microbiota alterations associated with the disease. In both MS and its purported murine model, experimental autoimmune encephalomyelitis (EAE), gastrointestinal symptoms and/or an altered gut microbiota have been reported together with increased intestinal permeability. In both EAE and MS, specific components of the microbiota have been shown to modulate both effector and regulatory T-cell responses and therefore disease progression, and EAE experiments with germ-free and specific pathogen-free mice transferred with microbiota associated or not with disease have clearly demonstrated the possible role of the microbiota in disease pathogenesis and/or progression. Here, we review the evidence that can point to two possible consequences of the gut-brain axis dysfunction in MS and EAE: 1. A pro-inflammatory intestinal environment and “leaky” gut induced by dysbiosis could lead to an altered communication with the CNS through the cholinergic afferent fibers, thereby contributing to CNS inflammation and disease pathogenesis; and 2. Neuroinflammation affecting efferent cholinergic transmission could result in intestinal inflammation as disease progresses.

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“…Therefore, in this study, CRS-R was used to evaluate the state of consciousness of patients.Research suggests that there is a bidirectional neuromodulation pathway between the brain and the gut, that is, the brain-gut axis (BGA). It is mediated by immune factors [ 16 , 17 ]. When the brain is damaged by irreversible ischemia and hypoxia, the function of the cerebral cortex decreases, resulting in a decline in the ability of the central nervous system to regulate the enteric nervous system, and the function of the enteric nervous system is relatively independent.…”

Section: Discussionmentioning

confidence: 99%

Establishment and evaluation of a prediction model for acute gastrointestinal injury in patients with prolonged disorder of consciousness

Hu²,

Zhou³

et al. 2022

BMC Gastroenterol

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Objective To establish a prediction model for acute gastrointestinal injury (AGI) in patients with prolonged disorder of consciousness (pDOC) and to evaluate and apply the prediction model. Methods The clinical data of 165 patients with pDOC admitted to the hyperbaric oxygen department from January 2021 to December 2021 were retrospectively reviewed, and the patients were divided into an AGI group (n = 91) and an N-AGI group (n = 74) according to whether AGI occurred. A prediction model was built by fitting multiple independent influencing factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the model, the Hosmer–Lemeshow (H–L) test was used to evaluate the goodness-of-fit of the model, and the ROC curve and calibration curve were drawn to evaluate the predictive performance. A nomogram was plotted to visualize the prediction model. Results According to the multivariate logistic regression analysis results, the prediction model was finally constructed with the CRS-R score, DAO, PCT, ALB, and I-FABP, and a nomogram was generated. The area under the ROC curve (AUC) of the prediction model was 0.931, the sensitivity was 83.5%, and the specificity was 93.2%. The data were divided into 5 groups for the H–L test (χ2 = 2.54, P = 0.468 > 0.05) and into 10 groups for the H–L test (χ2 = 9.98, P = 0.267 > 0.05). A calibration curve was drawn based on the test results, indicating that the prediction model has a good goodness-of-fit and good prediction stability. Conclusion The prediction model for AGI in pDOC patients constructed in this study can be used in clinical practice and is helpful to predict the occurrence of AGI in pDOC patients.

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Neuroimmunogastroenterology: At the Interface of Neuroimmunology and Gastroenterology

Cited by 8 publications

References 241 publications

Commensal-specific CD4 T cells promote inflammation in the central nervous system via molecular mimicry

Commensal-specific CD4 T cells promote inflammation in the central nervous system via molecular mimicry

The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?

Establishment and evaluation of a prediction model for acute gastrointestinal injury in patients with prolonged disorder of consciousness

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