Eric Hall

Background: Cardiovascular disease, due to build up of cholesterol laden atherosclerotic plaques in blood vessels, is the number one cause of death in the United States, accounting for 25% of all deaths.¹ Short chain fatty acids have been identified as beneficial to health previously, but further research has revealed that propionate has the greatest impact on circulating LDL cholesterol, a main factor in the progression of cardiovascular disease.²

Methods: Research sources were identified via multiple PubMed queries. For articles relating to diet and the gut microbiome terms such as “Mediterranean diet and the gut microbiome” were used. Further sources for the role of short chain fatty acids were found using terms like “Propionate’s role in lipid metabolism” and “Propionate effect on the gut microbiome.” Finally, the role of bacterial phylum on the production of short chain fatty acids was researched using terms such as “gut microbiome composition and short chain fatty acid production.”

Results: Oral administration of propionate has been shown to reduce LDL cholesterol by 15.9 mg/dL in one study among participants with LDL levels of >115 mg/dL at baseline.² Increasing levels of propionate have been shown to also increase the amount of satiety hormones PYY and GLP-1, which have been shown to reduce calorie intake and help with weight loss. ³ Additionally, it has also been shown that propionate increases the concentration of regulatory T cells and interleukin 10 (IL-10) within the wall of the large intestine, decreasing the expression of the cholesterol transporting channel protein Niemann-Pick C1 like protein (NPC1L1) and ostensibly decreasing inflammation within the surrounding area given IL-10’s known anti inflammatory properties.² The bacterial phylum Bacteroidetes and Firmicutes normally predominate the colonic bacteria population and are responsible for the majority of propionate synthesis through the fermentation of dietary fiber via the succinate and acrylate pathways.⁴ Whole grains such as whole grain wheat, corn, oat, millet, and barley along with psyllium fiber, lentils, and pea fiber have been shown to significantly increase the production of propionate by encouraging growth of these bacteria in the colon.⁵

Conclusions: The high prevalence of these foods within the Mediterranean diet therefore, hypothetically, contributes to the increased growth of Bacteroidetes and Firmicutes bacteria, increased production of propionate, increased levels of anti inflammatory IL-10 and regulatory T cells, and subsequent decreased LDL cholesterol compared to high fat Western diets, contributing to the observed prevention of cardiovascular disease among its adherents.

Works Cited:

1. Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association. Circulation. 2018;137(12):e67-e492.
2. Haghikia A, Zimmermann F, Schumann P, et al. Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism. European Heart Journal. 2021;43(6):518-533.
3. Chambers ES, Viardot A, Psichas A, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2014:gutjnl-2014-307913.
4. Reichardt N, Duncan SH, Young P, et al. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. Isme j. 2014;8(6):1323-1335.
5. Calatayud M, Van den Abbeele P, Ghyselinck J, Marzorati M, Rohs E, Birkett A. Comparative Effect of 22 Dietary Sources of Fiber on Gut Microbiota of Healthy Humans in vitro. Frontiers in Nutrition. 2021;8.