Title:Non-Celiac Gluten Sensitivity Triggers Gut Dysbiosis, Neuroinflammation, Gut-Brain Axis Dysfunction, and Vulnerability for Dementia
Volume: 14
Issue: 1
Author(s): Mak Adam Daulatzai
Affiliation:
Keywords:
Axis, cytokines, dysbiosis, gut-brain, lipopolysaccharide, microbiota, neuroinflammation, non-celiac gluten
sensitivity, oxidative-nitrosative stress, vagus nerve stimulation.
Abstract: The non-celiac gluten sensitivity (NCGS) is a chronic functional gastrointestinal disorder which is very
common world wide. The human gut harbors microbiota which has a wide variety of microbial organisms; they are
mainly symbiotic and important for well being. However, “dysbiosis” - i.e. an alteration in normal commensal gut
microbiome with an increase in pathogenic microbes, impacts homeostasis/health. Dysbiosis in NCGS causes gut
inflammation, diarrhea, constipation, visceral hypersensitivity, abdominal pain, dysfunctional metabolic state, and
peripheral immune and neuro-immune communication. Thus, immune-mediated gut and extra-gut dysfunctions, due to
gluten sensitivity with comorbid diarrhea, may last for decades. A significant proportion of NCGS patients may
chronically consume alcohol, non-steroidal anti-inflammatory drugs, and fatty diet, as well as suffer from various comorbid
disorders. The above pathophysiological substrate and dysbiosis are underpinned by dysfunctional bidirectional
“Gut-Brain Axis” pathway. Pathogenic gut microbiota is known to upregulate gut- and systemic inflammation (due to
lipopolysaccharide from pathogenic bacteria and synthesis of pro-inflammatory cytokines); they enhance energy harvest,
cause obesity, insulin resistance, and dysfunctional vago-vagal gut-brain axis. Conceivably, the above cascade of
pathology may promote various pathophysiological mechanisms, neuroinflammation, and cognitive dysfunction. Hence,
dysbiosis, gut inflammation, and chronic dyshomeostasis are of great clinical relevance. It is argued here that we need to
be aware of NCGS and its chronic pathophysiological impact. Therapeutic measures including probiotics, vagus nerve
stimulation, antioxidants, alpha 7 nicotinic receptor agonists, and corticotropin-releasing factor receptor 1 antagonist may
ameliorate neuroinflammation and oxidative stress in NCGS; they may therefore, prevent cognitive dysfunction and
vulnerability to Alzheimer’s disease.
