The Gut Brain-Axis in Neurological Diseases

Abstract

Recent evidence suggests that dysfunction of the gutbrain axis may be an important factor contributing to many diseases of the nervous system. Increased gut permeability associated with chronic gastrointestinal dysfunction, as well as changes in the composition of the gut microbiota could contribute to exposure of the enteric and central nervous system to pathogens and its metabolites, including endotoxins and pro-inflammatory cytokines. As a consequence, dysfunction of the host's immune system could contribute to an abnormal immunological response leading to auto-immune conditions, such as multiple sclerosis. So far, gut dysbiosis has been reported in association with Parkinson's disease, Alzheimer's disease, multiple sclerosis, neurodevelopmental and neuropsychiatric conditions, and cerebrovascular disease. These findings suggest that the possibility of targeting the gut microbiota could become a future therapeutic option to treat these conditions. However, before this knowledge can be useful in the clinical setting, more data is needed to establish clear causal relationships between dysfunction of the gut-brain axis and neurological diseases.

Mercury toxic effects on the intestinal mucosa assayed on a bicameral in vitro model: Possible role of inflammatory response and oxidative stress

“…At the systemic level, renal and neurological disorders in early stages of development are the ones that manifest the most in prolonged exposures to Hg. A series of preclinical observations link alterations in the brain-gut axis in the pathogenesis and pathophysiology of several neurological disorders (Barbosa and Reis Barbosa, 2020;Houser and Tansey, 2017;Martin et al, 2018). In children with attention deficit and hyperactivity disorder (ADHD), elevated serum zonulin levels (a marker of intestinal permeability) were associated with impaired social functioning compared to controls.…”

Gut dysbiosis in stroke and its implications on Alzheimer’s disease‐like cognitive dysfunction

“…Residing in the GI tract, the gut microbiome is composed of many highly influential microorganisms 65 . Alteration of the gut microbiome population may exacerbate disease symptoms of gut disorders and CNS diseases, such as AD 15,25 . Fluctuation in microbiota influences the brain via the gut‐brain axis, a bidirectional system with immune, endocrine, neural, and metabolic functions 65,66 .…”

“…Characterizing gut and brain microbiomes, in addition to microbiomes located in other organs, using single‐cell omics and transcriptomics 11,12 will be the first step in elucidating the stroke pathology and progressing cell‐based therapeutic strategies along with other neurological diseases 7 . Furthermore, Parkinson's disease (PD) models have recently revealed the use of potent microbiomes both as a biomarker and therapeutic target, 13,14 shifting from brain‐focused neurological diagnosis and treatments to analysis of peripheral in the progression of PD 15 . In fact, abnormal GI symptoms appear before motor symptoms in PD, suggesting that gut dysbiosis occurs prior to the onset of brain pathology 13,14 .…”

How Advanced Is Our Understanding of the Role of Intestinal Barrier Dysfunction in the Pathogenesis of Recurrent Urinary Tract Infections

“…Accordingly, disruption of the composition and functioning of the microbiota and/or the intestinal barrier may be associated not only with intestinal inflammation but also inflammatory bowel diseases. Current knowledge of the relevance of the intestinal barrier’s function is providing increasing evidence of its interaction with neurological and autoimmune disease, non-alcoholic fatty liver disease, obesity and diabetes, rheumatoid arthritis, and chronic kidney diseases ( Turner, 2009 ; Okumura and Takeda, 2017 ; Vancamelbeke and Vermeire, 2017 ; Meijers et al, 2018 ; Barbosa and Barbosa, 2020 ; Muehler et al, 2020 ). However, although antibiotics remain the basis of RUTIs treatment and prevention, there is a general lack of evidence for altered intestinal barrier function in patients with RUTIs.…”

“…These experimental data provide evidence of long-term antibiotic-induced impairment of intestinal permeability that facilitates the translocation of pathogenic bacteria, antigens, and other microbial products to the systemic circulation leading to chronic inflammation ( Johnson et al, 2015 ; Poole et al, 2017 ; Sharapatov et al, 2021 ). Gut microbiota-derived inflammation, so-called metabolic endotoxemia, has been recently demonstrated to play a key role in the pathogenesis of many diseases such as obesity, type 2 diabetes, pancreatitis, cardiovascular, systemic, kidney, liver, and bone diseases, as well as brain and mental disorders ( Durack and Lynch, 2019 ; Barbosa and Barbosa, 2020 ; Ilchmann-Diounou and Menard, 2020 ; Ren et al, 2020 ; Skinner et al, 2020 ; Zhou et al, 2020 ). Interestingly, endotoxemia and low-level inflammation caused by increased intestinal permeability have also been demonstrated in psychological stress and depression, which often coexist with RUTIs ( de Punder and Pruimboom, 2015 ; Trzeciak and Herbet, 2021 ).…”