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A new publication from researchers at the University of Colorado Boulder shows how gut bacteria increase the risk of cardiovascular disease by contributing to the stiffening of the blood vessels during aging. This study is the first to demonstrate that changes to the gut microbiome promote vascular aging and harm health [1].

The researchers treated groups of young and old mice with a range of antibiotics that are known to kill gut bacteria. Following this, they examined the vascular systems of the mice, particularly the lining of the blood vessels (endothelium) and the stiffness in their large arteries. Additionally, the researchers measured a number of biomarkers, including free radicals, antioxidants, pro-inflammatory cytokines, and nitric oxide in the blood.

After 3-4 weeks of treatment, the researchers once again measured the biomarkers and looked at the vascular system. There was no change in the young group of mice; however, the old mice saw significant improvement in both vascular health and biomarkers. The researchers note that the treatment had suppressed the microbiome of the aged mice and, in doing so, improved their health. Therefore, they concluded that something in the microbiome of old mice was contributing to vascular aging.

In order to determine what might be doing this, they took fecal samples from untreated young and old mice and compared the gut bacteria of both. They typically observed that the samples of old mice had more pro-inflammatory microbes, which are known to be linked to the onset of various diseases. They also noted that older mice had higher populations of Proteobacteria, a family that includes salmonella and desulfovibrio, a pro-inflammatory bacterium.

Finally, the researchers examined the gut bacteria metabolites in the blood of both young and old mice. The old mice had triple the metabolite trimethylamine N-oxide (TMAO) of the younger mice. TMAO is associated with an increased risk of atherosclerosis, strokes, and heart attacks.

The researchers propose that age-related changes to the gut microbiota lead to an increase of harmful metabolites, including TMAO, which enter the bloodstream and cause damage to the blood vessel walls through inflammation and oxidative stress.

They also make it clear that antibiotics should not be used to prevent cardiovascular diseases, as the range of side effects is considerable and using them during the experiment was not a refined approach. The microbiota contains a myriad of bacteria, many of which are beneficial to our health, so using antibiotics, which harms both good and bad bacteria, is not a good idea.

The next step would be to develop a compound that is capable of selectively targeting the bacteria that produce TMAO or blocking it in some other manner.

Abstract

Oxidative stress‐mediated arterial dysfunction (e.g. endothelial dysfunction and large elastic artery stiffening) is the primary mechanism driving age‐related cardiovascular diseases. Accumulating evidence suggests the gut microbiome modulates host physiology because dysregulation (‘gut dysbiosis’) has systemic consequences, including promotion of oxidative stress. The present study aimed to determine whether the gut microbiome modulates arterial function with ageing. We measured arterial function in young and older mice after 3–4 weeks of treatment with broad‐spectrum, poorly‐absorbed antibiotics to suppress the gut microbiome. To identify potential mechanistic links between the gut microbiome and age‐related arterial dysfunction, we sequenced microbiota from young and older mice and measured plasma levels of the adverse gut‐derived metabolite trimethylamine N‐oxide (TMAO). In old mice, antibiotics reversed endothelial dysfunction [area‐under‐the‐curve carotid artery dilatation to acetylcholine in young: 345 ± 16 AU vs. old control (OC): 220 ± 34 AU, P < 0.01; vs. old antibiotic‐treated (OA): 334 ± 15 AU; P < 0.01 vs. OC] and arterial stiffening (aortic pulse wave velocity in young: 3.62 ± 0.15 m s−1 vs. OC: 4.43 ± 0.38 m s−1; vs. OA: 3.52 ± 0.35 m s−1; P = 0.03). These improvements were accompanied by lower oxidative stress and greater antioxidant enzyme expression. Ageing altered the abundance of gut microbial taxa associated with gut dysbiosis. Lastly, plasma TMAO was higher with ageing (young: 2.6 ± 0.4 μmol L−1  vs. OC: 7.2 ± 2.0 μmol L−1; P < 0.0001) and suppressed by antibiotic treatment (OA: 1.2 ± 0.2 μmol L−1; P < 0.0001 vs. OC). The results of the present study provide the first evidence for the gut microbiome being an important mediator of age‐related arterial dysfunction and oxidative stress and suggest that therapeutic strategies targeting gut microbiome health may hold promise for preserving arterial function and reducing cardiovascular risk with ageing in humans.

Conclusion

The gut microbiome is becoming increasingly implicated in aging, and it is no real surprise that certain populations of bacteria produce harmful metabolites. With the growing popularity of research that links the microbiome to aging, it is likely that we will see more of it in the near future.

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Literature

[1] Brunt, V. E., Gioscia‐Ryan, R. A., Richey, J. J., Zigler, M. C., Cuevas, L. M., Gonzalez, A., … & Ackermann, G. (2019). Suppression of the gut microbiome ameliorates age‐related arterial dysfunction and oxidative stress in mice. The Journal of physiology.

CategoryNews, Research
About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
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