Gut–brain axis

Template:Unreviewed Gut Brain Axis The intestinal microbiota involves a wide diversity of microbial species and plays a crucial role in the development of innate and adaptive immune responses. They also influence physiological systems throughout life by modulating gut motility, intestinal barrier homeostasis, absorption of nutrients, and the distribution of somatic and visceral fat. The composition of the intestinal microbiota is established during the first few years of life and is likely shaped by multiple factors including maternal vertical transmission, genetic make up of the individual, diet, medications such as antibiotics, gastrointestinal infections and stress. The Gut Brain Axis describes any interaction between the gastrointestinal tract and the CNS. Indirect evidence from clinical studies Clinicians use on a routine basis laxatives and oral antibiotics to treat patients with altered mental status due to hepatic encephalopathy. Several clinical studies have also shown that patients with autism have altered composition of gut microbiota. These patients have seen short-term beneficial relief through antibiotic treatments. There are also multiple reports that cite patients developing psychosis after being administered with different antibiotics, as a consequence of their microbiota being affected because of the antibiotics. Direct evidence from animal studies Studies using chronic H. pylori infection in mice have shown that this pathogen alters gastric physiology, namely delayed gastric emptying and visceral sensitivity, with up-regulation of SP and CGRP containing nerves in the stomach and the spinal cord. The infection led to abnormal feeding behavior, characterized by frequent feeding bouts, but with less food consumed per feeding bout than controls, which is reminiscent of early satiety observed in patients with functional dyspepsia. The abnormal feeding pattern was accompanied by down-regulation of regulatory peptide Proopio-melanocortin (POMC) in the arcuate nucleus and up-regulation of the pro-inflammatory cytokine TNF-a in the median eminence (ME) of the hypothalamus. The ME is a part of the circumventricular organ, area of the brain where the blood brain barrier is relatively leaky, enabling metabolites/molecules from the systemic circulation to enter the CNS. Altered behavior and biochemical abnormalities persisted for at least two months postbacterial eradication suggesting that changes induced by chronic infection in the CNS may be long lasting or permanent. Perturbation of previously stable microbiota in healthy adult mice by oral administration of non-absorbable antimicrobials, a combination of neomycin, bacitracin and pimaricin, induced changes in colonic microbiota composition in SPF mice, with a marked increase in Firmicutes and decrease in proteobacteria. These changes in gut microbiota resulted in an increase in mouse exploratory behavior and altered BDNF levels in the hippocampus and amygdala.

Gut Brain Axis and Brain Function

Recent research suggests that the gut-brain axis, a bidirectional neurohumoral communication system in the human body, functions as a pathway for the gut microbiota to modulate brain function of its host. The postnatal microbial colonization of the gastrointestinal (GI) tract results in a long-lasting impact on the neural processing of sensory information regarding the hypothalamic-pituitary-adrenal stress response. In studies conducted, early postnatal bacterial colonization in germ free (GF) mice promoted the development of a central nervous system. The c-Fos activation in the paraventricular nucleus was rapidly induced by the inoculation of ''Bifidobacterium infantis''. Trytophan metabolism was modulated by Bifidobacterium infantis, suggesting that the normal gut microbiota can influence the precursor pool for serotonin, which is correlated to neurophysiological behavior. Anxiety-like behavior and central neurochemical changes were relieved in GF mice compared with specific pathogen free (SPF) mice. In addition, bacterial species Clostridial were found at an elevated level in the stools of children with autism than the stools of the children without.

Gut Brain Axis and Behavioral Phenotype

On the onset of birth, the immediate microbial colonization contributes to the development of epithelial barrier function, gut homeostasis, angiogenesis, innate adaptive immune function, and common neuro-developmental disorders (autism, schizophrenia). Compared to the specific pathogen free (SPF) mice, the germ free (GF) mice illustrated increased motor activity, reduced anxiety-like behavior, altered expression of synaptic plasticity-related genes, elevated noradrenaline, dopamine, and 5-hydroxytryptamine turnover in the striatum. When exposed to antibiotics, GI infections and stress, sharp changes in diet, the gut homeostasis and the central nervous system becomes imbalanced. Clinically, the introduction of probiotics, beneficial in the treatment of GI symptoms of disorder, help reduce anxiety, stress, and mood of patients with irritable bowel syndrome (IBS) and chronic fatigue. Lactobacillus reuteri, probiotic, is known to modulate the immune system, decrease anxiety, and reduce the stress-induced increase of corticosterone. Other probiotics can lower inflammatory cytokines, decrease oxidative stress, and improve nutritional status.

Gut-Brain-Liver Axis

The liver plays a dominant role in blood glucose homeostasis by maintaining a balance between the uptake and storage of glucose through the metabolic pathways of glycogenesis and gluconeogenesis. In recent studies, it is illustrated that intestinal lipids regulate glucose homeostasis involving a gut-brain-liver axis. The direct administration of lipids into the upper intestine increases the long chain fatty acyl-coenzyme A (LCFA-CoA) levels in the upper intestines and suppresses glucose production even under sub diaphragmatic vagotomy or gut vagal deafferentation. This interrupts the neural connection between the brain and the gut and blocks the upper intestinal lipids’ ability to inhibit glucose production. The gut-brain-liver axis can regulate the glucose homeostasis in the liver and provide potential therapeutic methods to treat obesity and diabetes.

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