What is the gut-brain axis?
The gut-brain axis is the communication that occurs between the gut and the brain through an intricate network of signaling molecules and pathways. Due to this bidirectional connection, various physiological processes can be influenced, including digestion, metabolism, immune response, and mood.
Clinical observations have made a connection between certain gastrointestinal diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), and mental health conditions such as anxiety and depression. This has brought about the idea that the gut-brain axis may have a role to play in these commonly occurring diseases with wide-ranging but mostly unknown mechanisms behind them.
Image Credit: Owlstone Medical Ltd
Research has indicated a connection between the interplay of the gut-brain axis and how physiological stress can exacerbate gut inflammation in specific bowel diseases.
The brain drives this process, which transmits signals to release stress hormones called glucocorticoids. A recent publication by Schneider et al. has shed some light on the role of glial cells in the gut. Glial cells trigger inflammation as they are targeted by glucocorticoids and subsequently release molecules that stimulate immune cells.1
The gut-brain axis is also influenced by the complex interplay of microbes in the gut, bringing about the concept of the microbiota-gut-brain axis. The complex dynamics of this relationship not only have an impact on the digestive system but also affect the immune system and the central nervous system.
For instance, an imbalanced microbiota can stimulate the mucosal immune system. Consequently, molecules such as inflammatory mediators and neuroactive substances are discharged and can pass through the bloodstream systematically around the body, which could change mood and behavior.
As well as facilitating a better comprehension of bowel conditions, the bidirectional communication of the gut-brain axis has become a critical factor in understanding mental health disorders. Metagenomic analysis has exposed a possible correlation between the gut microbiome and certain mental health conditions.
Although an understanding of the exact mechanisms underpinning the influence of gut microbes on the brain is still being formed, research indicates that metabolites or metabolite derivatives (volatile organic compounds, VOCs) originating in the gut microbes can help distinguish between individuals with mental health disorders and those that are otherwise considered healthy. Therefore, volatile compounds created in the gut that are detectable in exhaled breath may offer a novel approach when studying the gut-brain axis.
Breath analysis of the gut-brain axis
One method for the evaluation of VOCs is Breath Biopsy®. In a study published by Smolinska et al., breath VOCs and metagenomics were used to investigate individuals with Crohn’s Disease (CD), and demonstrated a connection between gastrointestinal disease, the gut microbiome, and exhaled breath composition.2
While the microbiome and its associated gastrointestinal diseases may influence the brain, as explained by the microbiota-gut-brain axis, which in turn could affect mood, to date, the direct correlation between gastrointestinal diseases, the gut microbiome, and its impact on the brain has not been made in exhaled breath studies.
However, a study conducted by Henning et al. utilized VOCs found in breath to detect schizophrenia and depression and connected two microbial-produced VOCs to the involvement of the microbiota–gut–brain axis.3
The study revealed five VOCs that had a 76.8% classification accuracy to categorize participants with major depression disorder (MDD) and distinguish them from healthy controls. Moreover, there was an 83.6% accuracy when distinguishing participants with schizophrenia from healthy controls and 80.9% when distinguishing participants with MDD from those with schizophrenia.
Of these five VOCs with reasonable classification accuracy, trimethylamine (TMA) and butyrate could be further associated with the involvement of the microbiota-gut-brain axis. The production of both trimethylamine and butyrate is associated with gut microbes. Therefore, these VOC changes indicate a relationship between microbial metabolites and neurological conditions.
It should be noted that during this study, blanks were not used to distinguish between breath and background signal, and other outliers such as nutrition and medication should also be considered.
Owlstone Medical has developed a standardized method to identify breath VOCs and distinguish them from those in ambient air; more information can be found here.
The most direct evidence showing a VOC passing through the blood-brain barrier through radio labeling. A study conducted by Frost et al. used PET-CT scanning to show how acetate can pass through the blood-brain barrier to be taken up by the brain.4
Like butyrate in the study above, acetate is another short-chain fatty acid that the gut microbes create, supporting the claim of a connection between the gut-brain axis. This indicates that VOCs produced by microbes in the gut can have direct involvement in the brain as they pass through the blood-brain barrier.
Owlstone offers a range of tools and expertise needed to incorporate breath analysis into ongoing gut-brain axis research. As demonstrated in this article, VOCs found in human breath can be leveraged as a tool to gain a deeper understanding of the gut-brain axis.
There are several advantages to conducting VOCs in breath studies. First, collecting breath samples is non-invasive and can be easily performed by individuals with various health conditions.
Second, the range of different breath VOCs can be potential biomarkers for numerous diseases and metabolic processes. Analysis of breath VOC composition offers scientists valuable insights into physiological and pathological bodily states. Moreover, breath sampling has the potential to be performed anywhere, from a clinical setting or even at home.
Owlstone Medical is a global leader in Breath Biopsy for disease detection and precision medicine, having recently developed the VOC Atlas. This database contains a range of validated VOCs typically found in the exhaled breath of healthy individuals and can be a valuable tool to help researchers evaluate the gut-brain axis.
For instance,TMA, the VOC discussed in Henning et al. used to distinguish subjects with mental conditions from healthy individuals, makes a connection between the activity of the microbiota and the gut–brain axis. This compound can be found in Owlstone’s VOC Atlas.
The VOC Atlas is continuously updated and will serve as a critical reference tool for the entire breath research community. For further information, please contact Owlstone to discuss how to investigate breath VOCs for your research interest.
References and further reading
- Schneider, K.M., et al., The enteric nervous system relays psychological stress to intestinal inflammation. Cell, 2023. DOI: 10.1016/j.cell.2023.05.001
- Smolinska, A., et al., Volatile metabolites in breath strongly correlate with gut microbiome in CD patients. Anal Chim Acta, 2018. 1025: p. 1-11. DOI: 10.1016/j.aca.2018.03.046
- Henning, D., et al., Gut-brain axis volatile organic compounds derived from breath distinguish between schizophrenia and major depressive disorder. J Psychiatry Neurosci, 2023. 48(2): p. E117-E125. DOI: 10.1503/jpn.220139
- Frost, G., et al., The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun, 2014. 5: p. 3611. DOI: 10.1038/ncomms4611
About Owlstone Medical Ltd
Owlstone Medical is developing a breathalyzer with a focus on non-invasive diagnostics for cancer, inflammatory disease and infectious disease, the company aims to save 100,000 lives and $1.5B in healthcare costs.
The company’s Breath Biopsy® platform has introduced a new diagnostic modality making it possible to discover novel non-invasive biomarkers in breath using a platform with the potential to transition to point-of-care. The award winning ReCIVA Breath Sampler ensures reliable collection of breath samples.
Breath Biopsy is supporting research into early detection and precision medicine with applications in cancer and a wide range of other medical conditions. Highly sensitive and selective, these tests allow for early diagnosis when treatments are more effective and more lives can be saved.
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