Bidirectional communication between the gut microbiome and the brain, known as the microbiota–gut–brain-axis, involves neuroendocrine-immune pathways. Metabolites produced when the amino acids are metabolized by the human gut microbiota can enter the bloodstream and have systemic effects. Australian and Ethiopian researchers investigated whether gut microbial metabolism of amino acids could interfere with the availability of neurotransmitter precursors to the brain in pigs. The results revealed that the radioactivity of the 14C- tyrosine was discovered in the brain after gut microbial fermentation.
Tyrosine is the precursor the catecholamines dopamine and noradrenaline. L-Tyrosine is converted to l-3,4-dihydroxyphenylalanine (L-DOPA) by the rate-limiting enzyme tyrosine hydroxylase and then catalyzed into dopamine. Downstream, β-hydroxylase converts dopamine to noradrenaline.
These findings imply that gut microbial fermentation of amino acids and neurotransmitter precursors like tyrosine, may affect brain function by interfering with the availability of neurotransmitter precursors to the brain.
There is a need to better understand the connection between nutrition, gut microbiota, and mental health. A dietary modulation of the microbiota–gut–brain-axis appears to be a promising approach for the prevention and treatment of mental health disorders.
About the study
The researchers developed a new workflow using the 14C radiolabeling to study complex nutrient-disease relationships. Pigs were chosen as the preclinical model because their digestive system is most similar to that of humans compared to other non-primate species.
The proposed workflow involves taking the 14C-labeled nutrient orally and after a short period of time for digestion and metabolism, collecting blood, urine, feces, organs, and tissues to determine the biodistribution of the 14C.
The biodistribution of the 14C-labeled metabolites is characterized by measuring the radioactivity in the samples using liquid scintillation counting. Ultra-high performance liquid chromatography and high-resolution mass spectrometry analysis were used to identify specific metabolites.
The scientists analyzed the biodistribution of the 14C-labeled omega-3 essential fatty acid, a-linolenic acid (ALA), and the 14C-labeled amino acid and neurotransmitter precursor tyrosine (Tyr) after gut microbial fermentation. ALA was chosed to test the workflow because the biodistribution of ALA is well documented, allowing for comparison between findings from the workflow and the literature to confirm that the workflow is effective at measuring the biodistribution of nutrients in tissues and organs.
The findings demonstrated that the radioactivity of the 14C-ALA was detected in tissues, indicating normal utilization of this essential fatty acid. Besides the high loss of the 14C-ALA radioactivity (52%) in urine and feces (likely due to the encapsulation technique), the remaining biodistribution of radioactivity showed the highest levels in liver, kidney and fat, and the lowest levels in brain tissues.
There was also a high loss of 14C-Tyr radioactivity (49%) in urine and feces. The most significant finding, however, was the discovery of the 14C-Tyr radioactivity in the brain (corresponding to 0.15% of the original dose), indicating that tyrosine fermented by microbes or its metabolites may be able to affect brain function.
This study has demonstrated that the radioactivity of the 14C- tyrosine was found in the brain after gut microbial fermentation. This confirms a relationship between nutrition, gut microbiota and the brain, as well as the possibility that metabolites of gut-fermented amino acid precursors to neurotransmitters such as tyrosine, may have an impact on brain functions.
The authors came to the conclusion that more study is needed to identify the compounds that enter the brain and how they affect brain function.
This article was published in Frontiers in Nutrition.
Murray M, et al. (2023) Demonstrating a link between diet, gut microbiota and brain: 14C radioactivity identified in the brain following gut microbial fermentation of 14C-radiolabeled tyrosine in a pig model. Front. Nutr. 10: 1127729. (Open Access) https://www.frontiersin.org/articles/10.3389/fnut.2023.1127729/full