The Gut-Brain Axis (And Gut Feelings)

How The Gut Controls Our Thoughts and Mood

Have you ever been told to go with your gut feeling?

This article describes why.

 
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Basics

 
 

The gut is approximately the same weight as the brain. R

The gut is inhabited by 10^13 to 10^14 microorganisms. This is significantly greater than the number of human cells. R

The microorganisms in the gut contain more than 100x as many genes as the human genome. R

The brain-gut axis is a two way street, so the brain can communicate with the gut and vice versa. R

Changes in the gut microbiota may cause:

  • Mental health issues (such as anxiety, depression, schizophrenia, and stress) R R
  • Clostridium difficile infection R
  • Irritable bowel syndrome (IBS) R
  • Pathogen colonization (i.e. vancomycin-resistant Enterococcus) R
  • Autoimmune and allergic diseases R
  • Obesity and metabolic disorders R
  • Neuropsychiatric disorders such as autism R
  • Parkinson's Disease R

From Birth To Adults

When we are babies, we have a low diversity of microbiota: mainly Proteobacteria and Actinobacteria. Over time out microbiota become more diverse with the presence of firmicutes and bacteroidetes. R R R

Vaginally delivered babies from healthy mothers that are breast-fed have neonatal microbiota. R

Those who are delivered by C-section, receive antibiotics, and aren't breast-fed, may develop:

  • Low stomach acidity R
  • Increased pathogenic bacteria in the gut R
  • Less microbial diversity R
  • Autism R
  • Cerebral Palsy R

Interestingly, rats separated from their mother had decreased fecal Lactobacillus levels on the third day. R

Also, the season of the birth makes a difference. For example, mothers nursing from July to October produced significantly less human milk oligosaccharides (important for beneficial gut bacteria in infants) compared to those nursing from November to June. R

Those in nursing homes tend to have far less diverse microbiota and a less varied diet. R

"Hygiene" and "Old Friends"

The hygiene hypothesis originated in 1989. According to this hypothesis, the reduced contact with microorganisms, especially during childhood, lifestyles away from nature and settlement mainly in large cities have resulted in an increased prevalence of allergic diseases. R

According to old friends hypothesis, Homo sapiens have been evolving and interacting for thousands of years with friendly microorganisms in the body. R 

Specifically, metabolites and nucleic acids produced by living microorganisms in the gut are transported into the human systemic circulation and lead to activation of inactive genes through epigenetic mechanisms, which can benefit health, lead to the development of various diseases and evolution. R R R

Vagus Nerve

The brain and gut are primarily connected via the vagus nerve. R

They are also connected via neural, endocrine, immune and metabolic pathways. R R

Irritable Bowel Syndrome

 
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IBS is typically generally derived from a biopsychosocial etiology and is correlated with depression and anxiety. R

Many studies suggest that trauma in childhood (especially sexual abuse (may be a factor of developing IBS). R

In IBS, aspects of the brain-gut axis communication are alteredR

Short Chain Fatty Acids

The brain is dependent on gut microbes for their metabolic products. R

Short chain fatty acids (SCFAs), such as butyrate, propionate, and acetate, are metabolic products of the gut's microbes. They may exert central effects on the body and brain through g-protein-coupled receptors.

Also, it is probably more likely that they act as epigenetic modulators, since they act on HDACs (histone deacetylases). R

Fasting serum levels SCFAs aren't different between IBS patients and controls, but right after a meal, SCFAs are significantly lower in IBS patients. R

Butyrate may help treat IBS during meals, but could be limited benefit. R

SCFAs also help: R

  • maintain energy balance
  • maintain metabolism
  • modulate adipose tissue
  • modulate liver tissue
  • modulate skeletal muscle and function

I like to take this butyrate for it's beneficial effects on the gut.

Mental Health

 
 

Dysbiosis can have a profound on brain function. R

Dysbiosis can happen for many reasons including: mode of birth delivery, diet, antibiotics, and drug use. R

Certain strains have been shown to produce neurotransmitters or precursors: R R 

  • Bifidobacteriam infantis - increaseses plasma tyrptophan and central serotonin 
  • Lactobacillus and Bifidobacterium spp - produce GABA (from msg)
  • Escherichia, Bacillus, and Saccharomyces spp - produce noradrenaline 
  • Candida, Streptococcus, Escherichaia, and Enterococcus spp - produce serotonin 
  • Bacillus - can produce dopamine
  • Lactobacillus - can produce acetylcholine and increase expression of eCB receptors in the brain R

Most of these are unlikely to cross the blood brain barrier, but they can affect the enteric nervous system. R

Depression

IBS and depression happen hand-in-hand.  They are both associated of very similar biomarkers of inflammation: R

  • IL-6
  • TNF-a
  • CRP

In one study, depressed patients had increased Bacteroidetes, Proteobacteria, and Actinobacteria, but significantly decreased Firmicutes. R

Also, depressives had increased levels of Enterobacteriaceae and Alistipes but reduced levels of FaecalibacteriumR

Rats given Lactobacillus rhamnosus for 28 days showed a decline in both anxiety and depression scores. R

Anxiety

Germ-free and pathogen-free mice are unable to feel anxiety. R

Germ-free rats had high plasma serotonin levels. R

Microbiota are required for feeling anxiety. R

For example, Campylobacter Jejuni administered orally to rats in subclinical doses led to anxiety-like behavior without an immune response. R

The most significant results were observed in the experiment where anxiety-like behavior obtained with high-fat diet was prevented by the administration of Lactobacillus helveticus for 21 days; when the experiment was duplicated using IL-10-deficient rats, no changes in anxiety were observed. These results showed the role of the immune system in the gut-brain axis. R

Stress

There is some evidence from rodent studies that stress can effect the gut barrier function (via degranulating mast cells). R

This allows LPS (lipopolysaccharide) and other molecules to gain access to the blood stream. R

This stimulates TLR4 (toll-like receptor 4) and other TLRs, resulting in the production of inflammatory cytokines. R

Lactobacillus farciminis to rats reduced the HPA axis response to stress (lowering ACTH and CRH). R

Treatment with Lactobacillus helveticus R0052 and Bifidobacterium longum showed psychological stress levels and urinary free cortisol levels were decreased. R

 
 

The Immune System

 
 

The gut microbiota affects the immune system homeostasis. R

Dysbiosis can cause autoimmune disorders. R

Interaction between the microbiota and the gut mucosa regulates the production of several proinflammatory cytokines and chemokines, such as IL-1, IL-8, IL-10 and TGF-β. R

Bacteria living in the gut interact with human cells. R 

This interaction occurs via one of the pattern recognition receptors (PRRs), namely the toll-like receptors. R R 

Ten TLRs have been identified in the immune system. R

These receptors are the first step in cytokine production pathways and are widely expressed in neurons. R R 

Stress on the Mucuosal Lining

 
 

The gut can produce cytokines. These cytokines can travel into the brain via the bloodstream. R

Cytokines effect the hypothalamus the most, since there is less blood brain barrier protecting that region of the brain. R

Stress (specifically cortisol) can disrupt the blood brain barrier via dysregulating the HPA axis. R

Stress can also disrupt the gut blood barrier, activating the immune system. R

Inflammatory cytokines such as interferon-alpha and IL-10 are known to cause depression and are blocked by antidepressants. R R R

Neurogenesis

Taking antibiotics can decrease neurogenesis and cognitive function. R

Probiotics and exercise can rescue neurogenesis and cognitive function. R

This is because Ly6Chi monocytes are crucial for brain homeostasis. R

Autism Spectrum Disorder

 
 

Autism Spectrum Disorder (ASD) has been increasingly rising over the past century. 

Effects of growing up in a more hygienic environment and changes in diet are mainly observed in developed countries, where the incidence of allergic diseases and autism is increasing. R

It is frequently correlated with GI distress. R

In experiments, germ-free mice had more ASD-like symptoms, such as social avoidance and abnormal social behaviors with other mice. When they added microbes back into the mice, they partially normalized their behavior patterns. R R

ASD patients may have gut permeability problems. Supplementation with Bacteriodes fragilis was shown to correct this problem. R

Oxytocin seems to play a role in autism. R

Lactobacillus Reuteri helped increase oxytocin levels in autistic patients. R

In stool sequencing, autistic children show: 

  • a significant decrease of the Bacteroidetes/Firmicutes ratio R
  • elevation of the amount of Lactobacillus spp R
  • modest elevation in Desulfovibrio spp -This seems to be associated with the severity of autism R

Probiotics helped fix these ratiosR

In one small study, a fecal matter transplant improved ASD GI and neurological symptoms overall. R V

Parkinson's Disease

 
 

In contrast to autism, Parkinson's Disease (PD) tends to be later in age, is the second most common neurodegenerative disorder and effects 1-2% of people over 65 years old. R

GI symptoms are associated with PD - constipation, appetite/weight loss, dysphagia, sialorrhea, and GERD. R

a-Synuclein, a presynaptic neuronal protein, is linked to PD. R

It has been found in the enteric nervous system (ENS). The ENS is a mesh-like system of neurons that governs the function of the gastrointestinal system. R

When sequencing stool samples in PD patients:

  • Prevotellaceae are significantly reduced (by ~80%) R
  • Enterobacteriaceae is high correlated with the severity of postural instability and gait difficulty R

FMTs (fecal matter transplants) may be a possible solution to PD in the future, but is still inconclusive. R

Brain-Gut Axis Fixes

 
 

Psychobiotics are probiotics or prebiotics that can be ingested to stimulate the growth of good bacteria and improve your mental health. R

Diet and Fermented Foods

Supplements

Probiotics

Depression:

Stress

Inflammation

Prebiotics

Prebiotics help promote gut microbiota growth, depression, anxiety, and stress. R

Devices

  • Deep transcranial magnetic stimulation R

Drugs

  • GHB (Gamma-hydroxybutyric acid) R
  • P2X7R antagonist R

Stay Away From

  • Antibiotics R
  • Stress R

More Research

  • Regulation of the gut microbiota using diet, probiotics and FMT may have important benefits for preventing and treating depression. R
  • Gut microbes can communicate with the brain through a variety of routes, including the vagus nerve, short-chain fatty acids (SCFAs), cytokines, and tryptophan. R