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Link between diet, gut microbes and mental health confirmed in new research

by Silvia Dropulich, Monash University

gut microbes - Credit Pixabay CC0 Public domain.jpg

Fermentation of ('resistant') protein in the gut (from highly processed foods) could release toxins into the body's circulation and affect the brain's access to neurotransmitter compounds, according to an international study


This animal study shows that gut microbial fermentation of 'resistant' dietary protein can produce potentially toxic metabolites, which disturb the availability to the brain of key amino acids needed to make key neurotransmitters such as dopamine, serotonin and noradrenaline.

The researchers used radio-labelling techniques to perform a detailed analysis of the metabolic fate of so-called 'resistant protein' in the diets of young pigs. This allowed them to track its breakdown into specific amino acids (the building blocks of protein) via digestion and fermentation by gut microbes, and to trace where these amino acids ended up.

'Resistant' protein is found in many ultra-processed, industrially-produced foods - whose manufacture typically involves heating ingredients to very high temperatures that are not achieved in ordinary cooking. This extreme heat treatment can alter the 'digestibility' of proteins - by our own enzymes, or by the trillions of microbes that live in our guts.

Previous research has already shown that high intakes of ultra-processed foods are strongly 'linked with' poor mental health - as well as with most chronic physical health disorders.  Numerous potential mechanisms could help to explain those associations - but this study focused on one set of these, as it is also established that:

  • diets rich in ultra-processed foods can lead to an unhealthy balance of gut microbes - known as 'dysbiosis'
  • gut dysbiosis can alter the metabolism of amino acids need to make key neurotransmitters needed for normal cell signalling
    • e.g the amino acid tryptophan - instead of being used to make serotonin - can instead be converted into different metabolites (such as kynurenic acid).  And such changes in tryptophan metabolism have long been implicated in low mood, depression and other mood disorders
    • Similarly the amino acid tyrosine can be converted into dopamine, adrenalin, or noradrenalin - but gut microbial fermentation can instead produce potentially toxic metabolites, and mimic dietary tyrosine depletion (also linked with depression and other mental health disorders) 

The researchers were able to demonstrate a clear step-wise pathway between dietary intake, gut microbiota and brain - consistent with their proposal that gut microbial fermentation of dietary resistant protein may affect brain function (by altering the supply of amino acid-derived neurotransmitters and/or the production of potentially toxic metabolites.)

However, further research is still needed to identify exactly which metabolities may reach the brain, and how these affect brain function.

And to map out a full causal pathway, clinical research in humans would still need to show that high resistant protein intake and production of amino acid fermentation metabolites predicted outcomes related to depression and anxiety.

For details of this research, see:

For a recent review of other mechanisms by which ultra-processed foods may affect brain function, see also:

And for a highly accessible and evidence-based account of the 'bigger picture' linking ultraprocessed foods with poor brain health, please see the new book by psychologist Kimberley Wilson:

10th March 2023, Medical Express


Fermentation of protein in the gut could release toxins into the body's circulation and affect the brain's access to neurotransmitter compounds, according to an international study by Monash University researchers.

The research, published in Frontiers in Nutrition, adds to the growing volume of work which seeks to understand the relationship between diet, the gut microbiota and mental health.

Tyrosine is an amino acid and precursor to key neurotransmitters, dopamine, adrenaline and noradrenaline, which have profound effects on mood, reward behavior, wakefulness and motor activity.

Dietary tyrosine depletion has been implicated in an increased risk of clinical depression.

When amino acids such as tyrosine are fermented by gut microbes, they may be converted to potentially toxic compounds, such as ammonia, amines, N-nitroso compounds, phenols, cresols, indoles and hydrogen sulfide rendering them unavailable as neurotransmitter precursors and mimicking dietary depletion.

Gut microbes also have the potential to convert amino acids to neurotransmitters (e.g., dopamine, serotonin) that function as signaling molecules in the enteric nervous system, with systemic and brain accessibility, known as the "gut-brain axis."

"The mechanisms that link diet, gut microbiota and mental health are challenging to investigate as this is a complex metabolic pathway," said lead study author Professor Louise Bennett from Monash University's School of Chemistry.

"Demonstrating that bacterial metabolites released in the gut can reach the brain, known as the 'gut-brain axis' is a key step in defining the relationship between nutrition and mental health," she said.

"Our study found that metabolites of gut-fermented protein and specifically amino acid precursors to neurotransmitters such as tyrosine, are potentially able to reach the brain and could influence brain functions including mood."

The research team found that gut microbial metabolism of amino acids from a high dietary intake of resistant protein diet could yield potentially toxic metabolites from fermented protein and disturb the availability of neurotransmitter precursors to the brain.

The researchers used isotope radiolabeling to test the biodistribution of specific nutrients in pigs, chosen for study as their digestive systems were the most closely matched to humans.

"The research has, for the first time, demonstrated a step-wise pathway between dietary intake, gut microbiota and brain," said Professor Bennett.

"We found that a high dietary intake of resistant protein diet alters the pool of amino acids available for normal digestion and metabolism and that digestion of amino acids by microbes in the gut produces unknown compounds that may be able to access the brain."