Issue 43 Gut Feeling

By Manny W Radomski

Gut feelings. Gut overview

Gut feelings. Gut overview

Healthy vs dysfunctional status


Since 1833, when US army surgeon William Beaumont reported the first scientific study of a link between the gut and the brain*, science has come a long way in tracing the path of contact between the two systems.

The gut-brain axis has been known for decades now. It refers to the connections and two-way communication between the gut and the brain. This axis is crucial for normal brain and gastrointestinal (GI or gut) development and functioning.

More recently, the gut microbiota (collective term for gut microbes) has emerged as a critical regulator of the gut-brain axis. The interactions between the gut microbiota and the gut-brain axis is now referred to as the microbiota-gut-brain axis.

Health and disease implications

Studies of the microbiota-gut-brain axis have been described as a paradigm shift in neuroscience. Emerging evidence shows that gut microbiota regulates the development and many functions of the brain.

Microbiota dysbiosis (disturbance and imbalance) and leaky gut barrier, which allows entry of undigested food particles, toxic waste, and harmful bacteria into the blood circulation, affect physiological, behavioral, cognitive, and memory functions of the brain, contributing to mental health conditions and neuropsychiatric disorders.

Extensive network

The microbiota-gut-brain axis is now shown to involve multiple overlapping systems. All of which engage in constant interactions.

These systems include:

  • nervous system (brain and spinal cord)
  • neural system (neurons, sensors and receptors)
  • neurotransmitters (serotonin and dopamine)
  • endocrine system (hormones and stress response regulation)
  • metabolic system (food and nutrition processing)
  • immune system (immune response and gut barrier to pathogens)

Evidence from across the fields of neuroscience, gastroenterology, and microbiology support the role of gut microbes in various metabolic, gastrointestinal, neurological diseases, and their influence in brain chemistry, mental and behavioral disorders.

Communication and interactions

Communication and interactions of the microbiota-gut-brain axis follow different pathways. They include:

  • direct activation of the vagus nerve
  • production of alteration of neurotransmitters
  • activation of immune signalling
  • via microbial metabolites
  • via stress-induced hormonal response
  • via pro-inflammatory cells

Interactions within these systems often co-occur in the gut, which is home to approximately 500 million nerve endings and the largest concentration of immune cells in the body.

Metabolites - important players

Metabolites derived from both the digestion and microbial fermentation of dietary and nutritional components may have a significant effect on brain processes and immune responses.

For example, manipulating the composition of the gut microbiota has been shown to influence the availability and regulation of fatty acids and tryptophan. In turn, fatty acids and tryptophan can interact with the immune system, thus regulating cellular immune responses.

As an important player in the microbiota-gut-brain axis, metabolites may serve as effective targets for clinical intervention.

Figures: The orchestra plays

The illustrations are simplified view of the interplaying factors and processes. They are not attempts to explain the underlying mechanism of the processes, most of which are still unclear and being investigated.



* Source: Stress is indigestible by Stanley Coren, WellnessOptions, updated 2017,


Fig 1: Healthy vs dysfunctional status

Reference: Moloney RD, et al (2014) The microbiome: stress, health and disease. Mamm Genome (2014) 25:49-74. doi: 10.1007/s00335-013-9488-5

Fig 2 : Mental health, neuropsychological, and behavioral states associated with gut dysbiosis and gut barrier integrity.

Reference: Kelly JR, et al (2016) Breaking down the barrier: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell. Neurosci. 9:392. doi: 10.3389/fncel.2015.00392Dinan TG and Cryan (2017) The microbiome-gut-brain axis in health and disease. Gasterterol Clin N Am 46 (2017) 77-89.doi: 10.1016/j.gtc.2016.09.007

Fung TC, et al (2017) Interactions between the microbiota, immune and nervous systems in health and disease. Nature Neuroscience 20(2):145-155. doi: 10.1038/nn.4476

Rieder R, et al (2017) Microbes and mental health: a review. Brain, Behavior and Immunity. doi: 10.1016/j.bbi.2017.01.016

Ho P and Ross D (2017) More than a gut feeling: the implications of the gut microbiota in psychiatry. Biological Psychiatry 2017. 81:e35-e37. doi: 10.1016/j.biopsych.2016.12.018

Frohlich EE et al (2016) Cognitive impairment by antibiotic-induced gut dysbiosis: analysis of gut microbiota-brain communication. Brain, Behavior, and Immunity 56(2016) 140-155, doi: 10.1016/j.bbi.2016.02.020

Kelly JR et al (2016) Brain-gut microbiota axis: challenges for translation in psychiatry. Ann Epidemiol 2016 pii:S1047-2797(16)30062-X. doi: 10.1016/j.annepidem.2016.02.008

Kelly JR, et al (2016) Breaking down the barrier: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell. Neurosci. 9:392. doi: 10.3389/fncel.2015.00392

Kelly JR et al (2016) Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res 2016: 109-118.

Parashar A and Udayabanu M (2016) Gut microbiota regulates key modulators of social behavior. European Neuropsychopharmacology (2016) 26: 78-91. doi: 10.1016/j.euroneuro.2015.11.002

Rogers GB et al (2016) From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Molecular Psychiatry (2016) 21: 738-748. doi: 10.1038/mp.2016.50

Wang HX and Wang YP (2016) Gut microbiota-brain axis. Chi Med J (Engl) 2016.129 (19): 2373-2380. doi: 10.4103/0366-6999.190667

Carabotti M et al (2015) The gut-brain axis – interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 2015: 28(2), 203-209.

Dinan TG et al (2015) Collective unconscious: how gut microbes shape human behavior. J of Psychiatric Research 63 (2015) 1-9. doi: 10.1016/j.jpsychires.2015.02.021

Sampson TR and Mazmanian SK (2015) Control of brain development, function, and behavior by the microbiome. Cell Host Microbe. 2015. 17(5):565-576. doi: 10.1016/j.chom.2015.04.011