Cardiometabolic Conditions and the Microbiome

Recent research suggests that the gut microbiome influences many health parameters, including cardiometabolic health. One large-scale study with 893 participants provides evidence that certain families of gastrointestinal bacteria can either positively or negatively affect cardiovascular health.1 Different compositions in the gut microbiome were correlated to both BMI and lipid levels, independent of genetics, age, and gender.1 Lower levels of bacterial families Christensenellaceae and Rikenellaceae, class Mollicutes, genus Dehalobacterium, and kingdom Archaea correlated with high BMI.1 The researchers estimated that 4.5-6% of BMI, triglycerides, and HDL variations could be explained by these variations in the microbiome, independent of other risk factors.1

In the following video, IFM educator Shilpa P. Saxena, MD, discusses how gut health and the microbiome impact cardiovascular health.

(Video Time: 02:00) Dr. Saxena is a board certified family physician who is a faculty member at the Academy of Integrative & Holistic Medicine, George Washington University’s Metabolic Medical Institute, and the Functional Medicine Coaching Academy. She is also a fellow & guest faculty for the Arizona Center for Integrative Medicine.

Although not conclusive, animal studies using fecal transfers allow us to better investigate the nature of the relationship between the microbiome and various diseases. One such analysis transplanted fecal microbiota from human donors to germ-free mice.2 The healthy human controls had a much richer and more diverse microbiome than the individuals with pre-hypertension and hypertension, who had overgrowth of bacteria such as Prevotella and reduced populations of bacteria correlated with improved health.2 After fecal transplantation, the germ-free mice who got material from individuals with hypertension soon exhibited elevated blood pressure themselves.2

One mechanism by which the microbiome affects the body is through generation of metabolites that alter host physiology3,4 and influence metabolic inflammation.5 After performing 16S rRNA gene sequencing in 531 Finnish men, researchers found gut microbiota correlated with fasting serum levels in fatty acids, amino acids, lipids, and glucose, as well as with levels of trimethylamine N-oxide (TMAO), a metabolite associated with coronary artery disease and stroke.6 The microbiome may also influence remote body sites through alterations in the short-chain fatty acids pathway and the bile acids pathways.3,7

The microbiome is also known to affect metabolism, and may contribute to insulin resistance and metabolic syndrome.6,8 In individuals with metabolic syndrome, arterial stiffness predicts cardiovascular risk.9 In a study of 617 women, analysis of the microbiome accounted for 8.3% of the variation in arterial stiffness, while visceral adiposity and insulin resistance only accounted for 1.8%. Examining the microbial makeup showed that butyrate-producing Ruminococcaceae bacteria were negatively correlated with arterial stiffness.9

This research is exciting in part because the microbiome changes rapidly in response to diet,10 making nutrition an important part of the microbiome-cardiometabolic equation.11,12 For example, research suggests that diets naturally rich in polyphenols and/or long-chain n-3 polyunsaturated fatty acids may significantly increase gut microbial diversity and bifidobacteria concentrations impacting glucose and lipid metabolism,13 and that bioactive compounds found in Mediterranean-style diets potentially adjust the ratio of Firmicutes/Bacteroidetes in the microbiome, improving the management and prevention of metabolic syndrome.14

Treating the gut using diet, probiotics, prebiotic foods, and other therapies may reduce risks for many cardiometabolic patients. IFM’s Cardiometabolic Food Plan, which is taught at the Cardiometabolic Advanced Practice Module (APM), provides an easily personalized patient education resource to improve nutrition and cardiac health, in part by effects on the microbiome.

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  1. Fu J, Bonder MJ, Cenit MC, et al. The gut microbiome contributes to a substantial proportion of the variation in blood lipids. Circ Res. 2015;117(9):817-824. doi:10.1161/CIRCRESAHA.115.306807
  2. Li J, Zhao F, Wang Y, et al. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5(1):14. doi:10.1186/s40168-016-0222-x
  3. Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res. 2017;120(7):1183-1196. doi:10.1161/CIRCRESAHA.117.309715
  4. Tang WH, Hazen SL. The gut microbiome and its role in cardiovascular diseases. Circulation. 2017;135(11):1008-1010. doi:10.1161/CIRCULATIONAHA.116.024251
  5. Tilg H, Zmora N, Adolph TE, Elinav E. The intestinal microbiota fueling metabolic inflammation. Nat Rev Immunol. 2020;20(1):40-54. doi:10.1038/s41577-019-0198-4
  6. Org E, Blum Y, Kasela S, et al. Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort. Genome Biol. 2017;18(1):70. doi:10.1186/s13059-017-1194-2
  7. Brown JM, Hazen SL. Microbial modulation of cardiovascular disease. Nat Rev Microbiol. 2018;16(3):171-181. doi:10.1038/nrmicro.2017.149
  8. Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535(7612):376-381. doi:10.1038/nature18646
  9. Menni C, Lin C, Cecelja M, et al. Gut microbial diversity is associated with lower arterial stiffness in women. Eur Heart J. 2018;39(25):2390-2397. doi:10.1093/eurheartj/ehy226
  10. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-563. doi:10.1038/nature12820
  11. Bennett BJ, Hall KD, Hu FB, McCartney AL, Roberto C. Nutrition and the science of disease prevention: a systems approach to support metabolic health. Ann N Y Acad Sci. 2015;1352:1-12. doi:10.1111/nyas.12945
  12. Attaye I, Pinto-Sietsma SJ, Herrema H, Nieuwdorp M. A crucial role for diet in the relationship between gut microbiota and cardiometabolic disease. Annu Rev Med. 2020;71:149-161. doi:10.1146/annurev-med-062218-023720
  13. Vetrani C, Maukonen J, Bozzetto L, et al. Diets naturally rich in polyphenols and/or long-chain n-3 polyunsaturated fatty acids differently affect microbiota composition in high-cardiometabolic-risk individuals. Acta Diabetol. 2020;57(7):853-860. doi:10.1007/s00592-020-01494-9
  14. Louis-Jean S, Martirosyan D. Nutritionally attenuating the human gut microbiome to prevent and manage metabolic syndrome. J Agric Food Chem. 2019;67(46):12675-12684. doi:10.1021/acs.jafc.9b04879

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