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A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis
Eelke Brandsma1, Niels J Kloosterhuis1, Mirjam Koster1,2
1From the Department of Pediatrics (E.B., N.J.K., M.K., D.C.D., M.R-M., M.G.L., A.d.B., J.F., F.K., B.M.B., M.W., M.H.H., B.v.d.S., D.P.Y.K.), University of Groningen, the Netherlands.
Circulation Research
|December 25, 2018
Summary
A proinflammatory gut microbiota from Caspase1 knockout (Casp1-/-) mice accelerates atherosclerosis in LDL receptor knockout (Ldlr-/-) mice. This involves increased inflammation and reduced beneficial gut bacteria and short-chain fatty acids.
Area of Science:
- Microbiology
- Immunology
- Cardiovascular Science
Background:
- Gut microbiota plays a role in inflammation and atherosclerosis.
- A causal link between gut microbiota, inflammation, and atherosclerosis requires further investigation.
Purpose of the Study:
- To determine if a proinflammatory microbiota from Caspase1 knockout (Casp1-/-) mice accelerates atherosclerosis in LDL receptor knockout (Ldlr-/-) mice.
Main Methods:
- Ldlr-/- mice received antibiotic treatment and fecal microbiota transplantation from Casp1-/- mice (or control Ldlr-/- mice).
- Mice were cohoused and fed either standard chow or a high-fat, cholesterol-rich diet.
- Inflammation, metabolism, intestinal health, and atherosclerotic phenotypes were analyzed.
Main Results:
- Mice receiving Casp1-/- microbiota showed a 29% increase in aortic root plaque size.
- Elevated circulating monocytes, neutrophils, and plasma proinflammatory cytokines were observed.
- Reduced abundance of short-chain fatty acid-producing bacteria and lower cecal short-chain fatty acid levels were found.
Conclusions:
- Transplanting a proinflammatory microbiota into Ldlr-/- mice exacerbates systemic inflammation and accelerates atherosclerosis.
- Gut microbiota composition significantly impacts the development of atherosclerosis.
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