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Chronic Functional Bowel Syndrome Enhances Gut-Brain Axis Dysfunction, Neuroinflammation, Cognitive Impairment, and Vulnerability to Dementia

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Abstract

The irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder world wide that lasts for decades. The human gut harbors a diverse population of microbial organisms which is symbiotic and important for well being. However, studies on conventional, germ-free, and obese animals have shown that alteration in normal commensal gut microbiota and an increase in pathogenic microbiota—termed “dysbiosis”, impact gut function, homeostasis, and health. Diarrhea, constipation, visceral hypersensitivity, and abdominal pain arise in IBS from the gut-induced dysfunctional metabolic, immune, and neuro-immune communication. Dysbiosis in IBS is associated with gut inflammation. Gut-related inflammation is pivotal in promoting endotoxemia, systemic inflammation, and neuroinflammation. A significant proportion of IBS patients chronically consume alcohol, non-steroidal anti-inflammatories, and fatty diet; they may also suffer from co-morbid respiratory, neuromuscular, psychological, sleep, and neurological disorders. The above pathophysiological substrate is underpinned by dysbiosis, and dysfunctional bidirectional “Gut-Brain Axis” pathways. Pathogenic gut microbiota-related systemic inflammation (due to increased lipopolysaccharide and pro-inflammatory cytokines, and barrier dysfunction), may trigger neuroinflammation enhancing dysfunctional brain regions including hippocampus and cerebellum. These as well as dysfunctional vago-vagal gut-brain axis may promote cognitive impairment. Indeed, inflammation is characteristic of a broad spectrum of neurodegenerative diseases that manifest demntia. It is argued that an awareness of pathophysiological impact of IBS and implementation of appropriate therapeutic measures may prevent cognitive impairment and minimize vulnerability to dementia.

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Abbreviations

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

ALI:

Acute lung injury

APP:

Amyloid precursor protein

BBB:

Blood–brain barrier

BOLD:

Blood oxygen level-dependent signal

CBF:

Cerebral blood flow

CD:

Celiac disease

CFGD:

Chronic functional gastrointestinal disorders

CgA:

Chromogranin A

CRF:

Corticotropin-releasing factor

CVO:

Circumventricular

DLPFC:

Dorsolateral prefrontal cortex

ENS:

Enteric nervous system

EPSC:

Excitatory postsynaptic currents

GIT:

Gastrointestinal tract

HC:

Healthy control

HF:

Heart failure

HLA:

Human leukocyte antigen

IBS:

Irritable bowel syndrome

IFN-γ:

Interferon gamma

IFL:

Airflow limitation

IL:

Interleukin

IL-1ra:

Interleukin-1 receptor antagonist

LPS:

Lipopolysaccharide

nAChR:

Nicotinic acetylcholine receptor

NAA:

N-acetyl-aspartate

NANC:

Non-adrenergic, non-cholinergic pathway

NCGS:

Non-celiac gluten sensitivity

NFκB:

Nuclear factor kappa B

NFT:

Neurofibrillary tangles

NSAID:

Non-steroidal anti-inflammatorY drug

NTS:

Nucleus tractus solitarius (nucleus of the solitary tract)

PSQI:

Pittsburgh sleep quality index

REM:

Rapid eye movement

SFO:

Subfornical organ

tau :

A microtubule-associated protein

TNF:

Tumor necrosis factor

VNS:

Vagus nerve stimulation

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  1. Sleep Disorders Group, EEE Department, Melbourne School of Engineering, The University of Melbourne, Grattan Street, 3rd Floor, Room No. 344, Parkville, VIC, 3010, Australia

    Mak Adam Daulatzai

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Daulatzai, M.A. Chronic Functional Bowel Syndrome Enhances Gut-Brain Axis Dysfunction, Neuroinflammation, Cognitive Impairment, and Vulnerability to Dementia. Neurochem Res 39, 624–644 (2014). https://doi.org/10.1007/s11064-014-1266-6

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