Gut Microbiota–Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice
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- Juneyoung Lee
- From the Department of Neurology, McGovern Medical School (J.L., J.d’A., L.A., V.Q., P.H., B.P.G., L.D.M., V.R.V.), The University of Texas Health Science Center at Houston
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- John d’Aigle
- From the Department of Neurology, McGovern Medical School (J.L., J.d’A., L.A., V.Q., P.H., B.P.G., L.D.M., V.R.V.), The University of Texas Health Science Center at Houston
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- Louise Atadja
- From the Department of Neurology, McGovern Medical School (J.L., J.d’A., L.A., V.Q., P.H., B.P.G., L.D.M., V.R.V.), The University of Texas Health Science Center at Houston
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- Victoria Quaicoe
- From the Department of Neurology, McGovern Medical School (J.L., J.d’A., L.A., V.Q., P.H., B.P.G., L.D.M., V.R.V.), The University of Texas Health Science Center at Houston
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- Pedram Honarpisheh
- From the Department of Neurology, McGovern Medical School (J.L., J.d’A., L.A., V.Q., P.H., B.P.G., L.D.M., V.R.V.), The University of Texas Health Science Center at Houston
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- Bhanu P. Ganesh
- From the Department of Neurology, McGovern Medical School (J.L., J.d’A., L.A., V.Q., P.H., B.P.G., L.D.M., V.R.V.), The University of Texas Health Science Center at Houston
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- Ahmad Hassan
- Department of Molecular and Cell Biology, Institute of Systems Genomics, The University of Connecticut, Storrs (A.H., J.G.)
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- Joerg Graf
- Department of Molecular and Cell Biology, Institute of Systems Genomics, The University of Connecticut, Storrs (A.H., J.G.)
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- Joseph Petrosino
- Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (J.P.)
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- Nagireddy Putluri
- Department of Molecular and Cellular Biology, Dan L. Duncan Comprehensive Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery (N.P.), Baylor College of Medicine, Houston, TX.
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- Liang Zhu
- Biostatistics and Epidemiology Research Design Core, Center for Clinical and Translational Sciences (L.Z.), The University of Texas Health Science Center at Houston
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- David J. Durgan
- Department of Anesthesiology (D.J.D., R.M.B.), Baylor College of Medicine, Houston, TX.
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- Robert M. Bryan
- Department of Anesthesiology (D.J.D., R.M.B.), Baylor College of Medicine, Houston, TX.
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- Louise D. McCullough
- From the Department of Neurology, McGovern Medical School (J.L., J.d’A., L.A., V.Q., P.H., B.P.G., L.D.M., V.R.V.), The University of Texas Health Science Center at Houston
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- Venugopal Reddy Venna
- From the Department of Neurology, McGovern Medical School (J.L., J.d’A., L.A., V.Q., P.H., B.P.G., L.D.M., V.R.V.), The University of Texas Health Science Center at Houston
説明
<jats:sec> <jats:title>Rationale:</jats:title> <jats:p>The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p>To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results:</jats:title> <jats:p> Aged male mice (18–20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2–3 months) or aged biome (18–20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers ( <jats:italic>Bifidobacterium longum</jats:italic> , <jats:italic>Clostridium symbiosum</jats:italic> , <jats:italic>Faecalibacterium prausnitzii</jats:italic> , and <jats:italic>Lactobacillus fermentum</jats:italic> ) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.</jats:p> </jats:sec>
収録刊行物
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- Circulation Research
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Circulation Research 127 (4), 453-465, 2020-07-31
Ovid Technologies (Wolters Kluwer Health)
