The gut microbiome is intricately involved in many of our bodily functions such as digestion, immunity and cognitive function. To gain a better understanding of how the microbiome can influence wellbeing, check out this summary of key microbial metabolites and the role they play in your health.
The last decade has seen a large increase in research about the community of microorganisms that live in our gut, called the gut microbiome. This research has shown that our gut microbiome plays an important role in our health through the production of various metabolites (break down products from the food microbes use for growth) that interact with our body1,2. Although several microorganisms and bacterial metabolites have been linked to specific disease states, we are only at the tip of the iceberg in understanding how and why these microbes and their metabolites are linked to our health.
One exciting way scientists are investigating these links is using an advanced DNA sequencing technology called metagenomics. With metagenomics, it is possible to ‘see’ all the genes in a microorganism and to understand what they might be doing, such as which metabolites they have the potential to produce. As this technology becomes more widespread, some metabolites are emerging in multiple studies as having a strong influence on health and disease.
Below are a few examples of key microbial metabolites that researchers are actively studying for the role they may play in our health:
Short-chain fatty acids
When gut bacteria break down fibre, they primarily produce short-chain fatty acids such as acetate, propionate and butyrate3. Scientists are discovering these short-chain fatty acids are incredibly important for our health because they are involved in several bodily functions4,5 such as:
- maintaining glucose stability
- regulating appetite
- providing fuel for intestinal cells
- maintaining the intestinal cell barrier
- regulating the immune system
- reducing inflammation
It is likely that as our understanding of how the gut microbiome influences health and disease advances, short chain fatty acids will be playing an important role.
3-indolepropionic acid (IPA) is a strong antioxidant produced by some gut bacteria that can help protect the nervous system from damage6. Research has shown low levels of IPA may play a role in the development of type 2 diabetes7,8 and research in animal models suggests IPA may also be involved in maintaining the gut barrier9. IPA is formed by breaking down the amino acid tryptophan. One study observed that consuming foods high in dietary fibre, and in particular rye, correlated with increased IPA production7.
One study observed that consuming foods high in dietary fibre, and in particular rye, correlated with increased IPA production7.
GABA is short for gamma-aminobutyric acid and is an important signalling molecule for the brain (called a neurotransmitter)10. GABA plays a key role in reducing the activity of nerve cells and low levels of GABA have been associated with anxiety and depression11,12. Although GABA is primarily produced by your body, some gut bacterial species can also produce (and consume) GABA. A couple of studies in animal models demonstrated that administering a bacterial species that can produce GABA results in changes to GABA receptors in the brain13 and the activity of sensory neurons14. This suggests it is possible for excess GABA produced by gut bacteria to be taken up by mammalian nerve cells, at least in animal models. It is still too early to know if the same applies in humans, but it offers a tantalising possibility for future research.
Lipopolysaccharides (LPS) are an important component of the cell wall of many bacteria, but when these bacteria die, the LPS is released into the gut where it can promote inflammation15. A high potential to produce LPS has been observed in individuals with colon cancer16, Crohn’s disease17 and insulin resistance18. Additionally, high blood levels of LPS have been observed in individuals with metabolic conditions such as heart disease, type 2 diabetes, non-alcoholic fatty liver disease and obesity19,20. Research suggests that high-fat diets can allow increased quantities of LPS to diffuse from the gut into the blood circulation19. Reducing the intake of fat can help reduce the ability of LPS to enter the bloodstream.
It is an exciting time in medicine as researchers are uncovering more about how the gut microbiome may influence our health and it is likely that metabolites such as the ones listed above, will be playing an important role. Tools such as metagenomic sequencing present a valuable opportunity for both researchers and individuals alike to gain a deeper insight into the gut microbiome.
- Sharon, G. et al. Specialized metabolites from the microbiome in health and disease. Cell Metab. 20, 719–730 (2014).
- Levy, M., Thaiss, C. A. & Elinav, E. Metabolites: messengers between the microbiota and the immune system. Genes Dev. 30, 1589–1597 (2016).
- den Besten, G. et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 54, 2325–2340 (2013).
- Morrison, D. J. & Preston, T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 7, 189–200 (2016).
- Koh, A., De Vadder, F., Kovatcheva-Datchary, P. & Bäckhed, F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell 165, 1332–1345 (2016).
- Bendheim, P. E. et al. Development of indole-3-propionic acid (OXIGONTM) for alzheimer’s disease. J. Mol. Neurosci. 19, 213–217 (2002).
- de Mello, V. D. et al. Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study. Sci. Rep. 7, 46337 (2017).
- Tuomainen, M. et al. Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals. Nutr. Diabetes 8, 35 (2018).
- Venkatesh, M. et al. Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4. Immunity 41, 296–310 (2014).
- Mazzoli, R. & Pessione, E. The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling. Front. Microbiol. 7, 1934 (2016).
- Möhler, H. The GABA system in anxiety and depression and its therapeutic potential. Anxiety Depress. 62, 42–53 (2012).
- Gabbay V, Mao X, Klein RG & et al. Anterior cingulate cortexγ-aminobutyric acid in depressed adolescents: Relationship to anhedonia. Arch. Gen. Psychiatry 69, 139–149 (2012).
- Bravo, J. A. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. U. S. A. 108, 16050–16055 (2011).
- Pokusaeva, K. et al. GABA‐producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. Neurogastroenterol. Motil. 29, e12904 (2017).
- Manco, M., Putignani, L. & Bottazzo, G. F. Gut Microbiota, Lipopolysaccharides, and Innate Immunity in the Pathogenesis of Obesity and Cardiovascular Risk. Endocr. Rev. 31, 817–844 (2010).
- Feng, Q. et al. Gut microbiome development along the colorectal adenoma–carcinoma sequence. Nat. Commun. 6, 6528 (2015).
- He, Q. et al. Two distinct metacommunities characterize the gut microbiota in Crohn’s disease patients. GigaScience 6, 1–11 (2017).
- Pedersen, H. K. et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535, 376 (2016).
- Moreira, A. P. B., Texeira, T. F. S., Ferreira, A. B., do Carmo Gouveia Peluzio, M. & de Cássia Gonçalves Alfenas, R. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br. J. Nutr. 108, 801–809 (2012).
- Cani, P. D. et al. Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes 56, 1761 (2007).