Irritable Bowel Syndrome, Depression, and Neurodegeneration: A Bidirectional Communication from Gut to Brain

Abstract

Patients with irritable bowel syndrome (IBS) are increasingly presenting with a wide range of neuropsychiatric symptoms, such as deterioration in gastroenteric physiology, including visceral hypersensitivity, altered intestinal membrane permeability, and gastrointestinal motor dysfunction. Functional imaging of IBS patients has revealed several abnormalities in various brain regions, such as significant activation of amygdala, thinning of insular and anterior cingulate cortex, and increase in hypothalamic gray matter, which results in poor psychiatric and cognitive outcomes. Interrelations between the enteric and central events in IBS-related gastrointestinal, neurological, and psychiatric pathologies have compelled researchers to study the gut-brain axis-a bidirectional communication that maintains the homeostasis of the gastrointestinal and central nervous system with gut microbiota as the protagonist. Thus, it can be disrupted by any alteration owing to the gut dysbiosis or loss of diversity in microbial composition. Available evidence indicates that the use of probiotics as a part of a balanced diet is effective in the management of IBS and IBS-associated neurodegenerative and psychiatric comorbidities. In this review, we delineate the pathogenesis and complications of IBS from gastrointestinal and neuropsychiatric standpoints while also discussing the neurodegenerative events in enteric and central nervous systems of IBS patients and the therapeutic potential of gut microbiota-based therapy established on clinical and preclinical data.

Keywords: depression; gut dysbiosis; irritable bowel syndrome; microbiota-gut-immune-glia axis; neurodegeneration.

Figure 1

Mechanisms of prebiotic and probiotic action in modulating bidirectional gut−brain axis. A healthy human gut is unable to digest macronutrients, including plant-derived polysaccharides. Probiotics produce enzymes to digest the fibers and carbohydrates to produce short-chain fatty acids (SCFA) in the form of lactic acid and acetic acids. Prebiotics serve as a source of nutrition for the stimulation and propagation of commensal bacteria in the gut. The presence of SCFA reduces the pH of the intestinal lumen, preventing the growth of pathogen, or it has anti-microbial activity. Certain probiotic strains could restore the intestinal barrier function by increasing the expression of tight junction proteins as well as mucus-secretion genes. They also help modulate the intestinal immune system by reducing the amount of pro-inflammatory cytokines. In addition, probiotics exhibit neuromodulatory effects by enhancing neurochemical production in the gut, including serotonin, GABA, tryptamine, noradrenaline, dopamine, and acetylcholine. As cytokines and neurotransmitters will impair the integrity of the blood−brain barrier, this leads to potentially damaging effects of inflammatory or pathogenic elements that link to the central nervous system to secrete stress hormones.