Gut Microbiome Communication: The Gut-Organ Axis
The are known as the human gut microbiota. The gut microbiome performs numerous functions, including protecting the barrier integrity of the intestine, producing vitamins such as B12 and K and regulating the immune system. The gut microbiome metabolizes available substrates and releases various metabolites, such as (SCFA) and neuro-active compounds, that become the biochemical signals that travel through the various axes and . This innate communication system demonstrates the impact the gut microbiome has on human physiology.
Gut-Brain Axis
Neurologically active compounds produced by the gut microbiome affect by regulating production, metabolism and transmission of neurotransmitters. Microbes in the gut metabolize the amino acid tryptophan into and other metabolites, regulating serotonin levels in the brain. Cortisol release during slows the , which control gastrointestinal peristalsis and chyme production in the stomach and small intestine. Disrupted microbial composition in the gut is an observed outcome. Furthermore, studies demonstrate patients with anxiety have elevated levels of pro-inflammatory cytokines and diminished anti-inflammatory, SCFA-producing microbiome.
Gut-Skin Axis
Skin and the gastrointestinal tract share the following common traits, which form the :
- Colonized by microbiota.
- Rich in immune cells, nerve- and blood-supply.
- Large organs with total surface area measuring >20 meters squared, on average.
- Lined with epithelial cells that form a protective barrier from their outside environments.
is reported to involve multiple channels including the . For example, manifests as gastrointestinal reactions (stomach cramps, diarrhea), immune reactions (runny nose, sneezing, itching) and skin reactions (rash, hives). Studies have found exposure to peanut protein from indoor dust through non-intact skin can elicit peanut allergy in patients. Evidence suggests close to 10% of patients with irritable bowel syndrome have . Furthermore, study participants with demonstrated increased serum vitamin-D levels and greater gut microbiome diversity, compared to those taking vitamin-D supplements alone. These examples illustrate bi-directional communication between the gut and skin via the immune and endocrine systems.
Gut-Pancreas-Liver Axis
In addition to serotonin, gut microbes metabolize tryptophan into the organic compound . Indole has been shown to regulate short- and long-term (GLP-1) secretion, a hormone released in the intestine to regulate in response to a meal. GLP-1 stimulates pancreatic insulin production and reduces glucose production and insulin clearance by the liver. Microbial fermentation of dietary fiber yields SCFA, which are also known to stimulate GLP-1 secretion.
Dysbiosis Is Linked to Diseases of the Body and Mind
Disruption to the gut microbiome composition is known as . A consequence of dysbiosis is altered amounts of metabolites produced by the microbiome, which may be tied to the development of various diseases, like , and . Although more research is needed to fully understand the mechanisms explaining dysbiosis and disease, low-grade inflammation is a common theme in conditions associated with gut dysbiosis.
Lipopolysaccharides Trigger Immune Responses and Inflammation
Members of the gut microbiota synthesize lipopolysaccharides (LPS), which are also a part of the gram-negative bacterial cell wall Dysbiosis is often characterized by an increased phyla ratio associated with decreased SCFA, increased LPS and inflammation. In the dysbiotic state, increases in LPS disrupt intestinal barrier integrity and trigger , depending on their source. This inflammatory response further damages gut barrier integrity, allowing translocation of gut microbes and LPS directly into the bloodstream or through the portal circulation.
Increased concentration of LPS in the gut and in circulation is associated with and even insulin resistance. LPS bind to Toll-like receptors (TLR), a receptor site expressed on most cells. LPS binding to TLR activates cytokine-induced inflammation observed in , , and .
Mechanistic (Mammalian) Target of Rapamycin Implicated In Diabetes and Acne
(mTOR) is a protein kinase enzyme involved in different metabolic processes. MTOR binds with other proteins to form complexes involved in specific metabolic processes. Overactivation of the mTOR pathway from increased microbial production of , a histidine metabolite, is implicated in prediabetes and type 2 diabetes. MTOR activation also increases .
Reduced SCFA Production Linked to Autism, Epilepsy and Schizophrenia
Dysbiosis with reduced production of SCFA, particularly butyrate, and high levels of cytokines are found in children and teens with . Metabolism of amino acids tryptophan and glutamate is altered. This alteration reduces production of serotonin and , 2 important inhibitory neurotransmitters also associated with and .
The Interplay between the Gut Microbiome, the Gut-Organ Axis and Dysbiosis
The state of your health might just lie within your intestines. One’s overall health can be explained, in part, by the diversity and composition of intestinal microbes and their genes, collectively known as the human gut microbiome. The gut-organ axis is a bi- or multi-directional, multi-channel communication system that allows the gut and extraintestinal organs to communicate with one another and is fundamental to understanding how the gut microbiome affects human health.
A growing number of studies are linking dysbiosis to acute and chronic diseases. In dysbiosis, pro-inflammatory microbiota produce metabolites that reach extraintestinal organs via distinct gut-organ axes, setting the stage for disease.
A key takeaway from the scientific evidence surrounding the gut microbiome, the gut-organ axis and dysbiosis is that health can be impaired, improved and even restored, depending on the microbiome composition and the anti- or pro-inflammatory nature of their metabolites. It is these metabolites that are the biochemical signals impacting physiology and, thus, health and disease via the gut-organ axis.
Microbial communities exist on, in and around people, plants, animals and the environment, making the microbiome relevant to nearly all facets of life. Learn more about the function and compositions of these microbial communities.
