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Research suggests, with increasing evidence, that the gut microbiome has a strong correlation with the occurrence, progression, and treatment of cardiovascular diseases.¹ Scientists speculate that gut microbiota dysbiosis, including an impaired mucosal barrier, gut microbiota–generated metabolites, and the related signaling pathway, may serve as explanations for some of the mechanisms about the occurrence and development of cardiovascular diseases.¹

A cross-sectional study published in 2023, of 8,973 participants aged 50 to 65, suggests a link between certain bacteria living in the gut (taken by fecal sample) and coronary atherosclerotic plaques.² Sixty-four species were associated with a coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. As the largest cardiovascular and metagenomics study to date, this research provides further evidence that oral species are commonly transmitted to the gut, suggesting that the gut and oral microbiota may be connected.²

Another large-scale study with 893 participants suggests that certain families of gastrointestinal bacteria can either positively or negatively affect cardiovascular health.³ Different compositions in the gut microbiome were correlated to both BMI and lipid levels, independent of genetics, age, and gender. Lower levels of bacterial families Christensenellaceae and Rikenellaceae, class Mollicutes, genus Dehalobacterium, and kingdom Archaea correlated with high BMI. The researchers estimated that 4.5-6% of BMI, triglyceride, and HDL variations could be explained by these variations in the microbiome, independent of other risk factors.³

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

Fecal Transfers

Fecal microbiota transplantation (FMT) may affect the course of some cardiometabolic diseases, including metabolic syndrome and type 2 diabetes (T2D).⁴ A recent study suggests that a single oral FMT administration, coupled with daily low-fermentable fiber supplementation, may improve insulin sensitivity and microbial diversity in people with severe obesity and metabolic syndrome.⁵

Another small 2017 human study (n=38) investigated the effect of lean donor (allogenic) versus own (autologous) FMT to male recipients with metabolic syndrome.⁵ Results after the allogenic FMT indicated a significant improvement in insulin sensitivity at six weeks, accompanied by altered microbiota composition.⁵ However, the benefits and microbiota composition changes were short-term, returning to baseline measurements at 18 weeks. Investigators noted that participants did not deviate from their regular lifestyle practices, including diet, during the study and that this may have impacted the FMT benefit.⁶

In an animal study, Wang et al found that rebuilding the microbiota in T2D mice by FMT improved insulin resistance and attenuated pancreatic islet β-cell destruction, thereby alleviating hyperglycemia.⁷ Study results on FMT in cardiometabolic diseases are varied, and clinical application may be limited.⁴

Microbiota Mechanisms & Metabolism

One mechanism by which the microbiome affects the body is through generation of metabolites that alter host physiology^8-10 and influence metabolic inflammation.¹¹ 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.¹² Recent systematic reviews have associated high circulating levels of TMAO with cardiometabolic disorders in adults,¹³ as well as both major adverse cardiovascular events and all-cause mortality.¹⁴ The microbiome may also influence remote body sites through alterations of pathways such as the short-chain fatty acids and bile acids pathways.^8,15

The gut microbiome is also known to affect metabolism and may contribute to insulin resistance and metabolic syndrome.^12,16 In individuals with metabolic syndrome, arterial stiffness predicts cardiovascular risk.¹⁷ 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.¹⁷

Dietary Impacts

This research is exciting in part because the microbiome changes rapidly in response to diet,¹⁸ making nutrition an important part of the microbiome-cardiometabolic equation.^19,20 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,²¹ 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.²²

Treating the gut using diet, probiotics, prebiotic foods, and other therapies may reduce risks for many cardiometabolic patients. IFM’s Cardiometabolic Food Plan is one therapeutic resource that is easily personalized and helps to support cardiac and metabolic health, in part by effecting the microbiome. Learn more about cardiometabolic conditions and clinical applications that support your patient’s health journey at IFM’s upcoming Cardiometabolic Advanced Practice Module (APM).

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References

1. Wang L, Wang S, Zhang Q, He C, Fu C, Wei Q. The role of the gut microbiota in health and cardiovascular diseases. Mol Biomed. 2022;3(1):30. doi:10.1186/s43556-022-00091-2
2. Sayols-Baixeras S, Dekkers KF, Baldanzi G, et al. Streptococcusspecies abundance in the gut is linked to subclinical coronary atherosclerosis in 8973 participants from the SCAPIS cohort. Circulation. 2023;148(6):459-472. doi:10.1161/circulationaha.123.063914
3. 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
4. Zheng L, Ji YY, Wen XL, Duan SL. Fecal microbiota transplantation in the metabolic diseases: current status and perspectives. World J Gastroenterol. 2022;28(23):2546-2560. doi:10.3748/wjg.v28.i23.2546
5. Mocanu V, Zhang Z, Deehan EC, et al. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial. Nat Med. 2021;27(7):1272-1279. doi:10.1038/s41591-021-01399-2
6. Kootte RS, Levin E, Salojärvi J, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 2017;26(4):611-619. doi:10.1016/j.cmet.2017.09.008
7. Wang H, Lu Y, Yan Y, et al. Promising treatment for type 2 diabetes: fecal microbiota transplantation reverses insulin resistance and impaired islets. Front Cell Infect Microbiol. 2020;9:455. doi:10.3389/fcimb.2019.00455
8. Tang W, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res. 2017;120(7):1183-1196. doi:10.1161/CIRCRESAHA.117.309715
9. Tang W, Hazen SL. The gut microbiome and its role in cardiovascular diseases. Circulation. 2017;135(11):1008-1010. doi:10.1161/CIRCULATIONAHA.116.024251
10.  Ottosson F, Brunkwall L, Smith E, et al. The gut microbiota-related metabolite phenylacetylglutamine associates with increased risk of incident coronary artery disease. J Hypertens. 2020;38(12):2427-2434. doi:10.1097/HJH.0000000000002569
11.  Tilg H, Zmora N, Adolph TE, Elinav E. The intestinal microbiota fuelling metabolic inflammation. Nat Rev Immunol. 2019;20(1):40-54. doi:10.1038/s41577-019-0198-4
12.  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
13.  Abbasalizad Farhangi M, Vajdi M. Gut microbiota–associated trimethylamine N-oxide and increased cardiometabolic risk in adults: a systematic review and dose-response meta-analysis. Nutr Rev. 2021;79(9):1022-1042. doi:10.1093/nutrit/nuaa111
14.  Guasti L, Galliazzo S, Molaro M, et al. TMAO as a biomarker of cardiovascular events: a systematic review and meta-analysis. Intern Emerg Med. 2021;16(1):201-207. doi:10.1007/s11739-020-02470-5
15.  Brown JM, Hazen SL. Microbial modulation of cardiovascular disease. Nat Rev Microbiol. 2018;16(3):171-181. doi:10.1038/nrmicro.2017.149
16.  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
17.  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
18.  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
19.  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):1-12. doi:10.1111/nyas.12945
20.  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(1):149-161. doi:10.1146/annurev-med-062218-023720
21.  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
22.  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