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Diet → Gut →Brain axis: role of Short Chain Fatty Acids (SCFAs)

Diet → Gut →Brain axis: role of Short Chain Fatty Acids (SCFAs)

Short-Chain Fatty Acids (SCFAs)

Short-Chain Fatty Acids result from bacterial fermentation of dietary fibers and resistant starch in our gut. They constitute the main source of nutrition for the cells in the colon and play an important role in our health. It was found that SCFAs can help reduce the risk of inflammatory diseases, digestive disorders, type 2 diabetes, and colon cancer as well as play an important role in the microbiota-gut-brain crosstalk.

Acetic acid, propionic acid, and butyric acid constitute the three most common SCFAs. Acetic acid, the shortest of the fatty acids, operates as an energy source for our muscles and also helps to keep the pH of the gut environment stable. Butyric acid has anti-inflammatory effects and contributes to cholesterol stabilization. Research has shown that it is involved in the treatment/prevention of Crohn’s disease, colon cancer [1] and type 2 diabetes. Propionic acid, like butyrate, protects against inflammations and may play a role in the prevention of colon cancer. Moreover, this SCFA is essential for our immune system and oral health.

Gut microbiota plays an important role in the bidirectional communication between the gut-brain axis, through various signaling mechanisms. Specifically, research has related the levels of SCFAs to mental and neurological issues [2].

SCFAs food sources

Dietary choices can affect the amount of SCFAs produced in our system. Higher quantities of SCFAs are present in high fiber and low-fat diets, compared to diets with a lower fiber intake [3] As SCFAs are generated through bacterial fermentation of dietary fibers, eating fiber-rich foods (fruits, vegetables, legumes, etc.) leads to increased production of these compounds. Moreover, foods made via bacterial fermentation like butter, cheese, and yogurt, also constitute rich sources of SCFAs [4].

It becomes clear that detecting the concentration of SCFAs in the human body can provide valuable information on one’s nutritional status and therefore health, making timely and beneficial interventions easier.

In Nutrishield, case study III focuses on the assignment of the (co)relation between various metabolites from exhaled breath and dietary quality for children with various diet habits and cognitive abilities. For this, RU has analyzed the breath samples and together with CU performed multivariate modelling to relate these data to the nutritional status. Our preliminary results indicate the potential of breath metabolites and specifically of SCFA to predict nutritional status in children. The next step is to investigate how significant breath metabolites relate to specific elements of the diet (e.g. SCFA in relation to fiber intake).

Furthermore, a non-invasive method via exhaled breath has been validated for measuring and analyzing the SCFA levels [5]. This uses single exhalation and can be applied safely to all categories of participants, including children.




Health profits

Food Sources

Acetic acid

Energy source for muscles

 pH stabilization

Appetite control

dairy products, bread, pasta

 liquid eggs

Butyric acid

Energy source for colon cells

Anti-inflammatory  effects

Protection against cancer

Neural system and brain protection

 cheese, butter,  milk

Propionic acid

Immune system protection

Oral health

Anti-inflammatory  effects

Protection against cancer

bread, pasta-noodles, aged cheese, eggs




  1. Scheppach W, Bartram HP, Richter F. Role of short-chain fatty acids in the prevention of colorectal cancer. Eur J Cancer. 1995 Jul-Aug;31A(7-8):1077-80.
  2. Silva, Y.P., Bernardi, A., Frozza, R.L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol. 2020, 11, 25.
  3. Ou, J., Carbonero, F., Zoetendal, E. G., Delany, J. P., Wang, M., Newton, K., et al.  Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am. J. Clin. Nutr. , 2013, 98, 111–120.
  4. Shimizu H, Masujima Y, Ushiroda C, Mizushima R, Taira S, Ohue-Kitano R, Kimura I. Dietary short-chain fatty acid intake improves the hepatic metabolic condition via FFAR3. Sci Rep. 2019, 9(1):16574.
  5. Henderson, B., Lopes Batista, G., Bertinetto, C. G., Meurs, J., Materić, D., Bongers, C. C. W. G., et al.. Exhaled Breath Reflects Prolonged Exercise and Statin Use during a Field Campaign. Metabolites (2021), 11, 192.


NUTRISHIELD aims at creating a personalised platform for the young. The platform will consist of novel methods & techniques, which analyse a wide range of biomarkers related to nutrition and health disorders.