دورية أكاديمية

Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice.

التفاصيل البيبلوغرافية
العنوان: Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice.
المؤلفون: Lee J; 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., d'Aigle J; 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., Atadja L; 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., Quaicoe V; 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., Honarpisheh P; 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., Ganesh BP; 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., Hassan A; Department of Molecular and Cell Biology, Institute of Systems Genomics, The University of Connecticut, Storrs (A.H., J.G.)., Graf J; Department of Molecular and Cell Biology, Institute of Systems Genomics, The University of Connecticut, Storrs (A.H., J.G.)., Petrosino J; Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (J.P.)., Putluri N; 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., Zhu L; Biostatistics and Epidemiology Research Design Core, Center for Clinical and Translational Sciences (L.Z.), The University of Texas Health Science Center at Houston., Durgan DJ; Department of Anesthesiology (D.J.D., R.M.B.), Baylor College of Medicine, Houston, TX., Bryan RM Jr; Department of Anesthesiology (D.J.D., R.M.B.), Baylor College of Medicine, Houston, TX., McCullough LD; 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., Venna VR; 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.
المصدر: Circulation research [Circ Res] 2020 Jul 31; Vol. 127 (4), pp. 453-465. Date of Electronic Publication: 2020 May 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Baltimore, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Md. Grune & Stratton.
مواضيع طبية MeSH: Fecal Microbiota Transplantation*, Fatty Acids, Volatile/*biosynthesis , Gastrointestinal Microbiome/*physiology , Infarction, Middle Cerebral Artery/*therapy , Ischemic Stroke/*therapy, Age Factors ; Animals ; Bifidobacterium longum/metabolism ; Brain Chemistry ; Clostridium symbiosum/metabolism ; Faecalibacterium prausnitzii/metabolism ; Fatty Acids, Volatile/analysis ; Fatty Acids, Volatile/blood ; Feces/chemistry ; Interleukin-17/biosynthesis ; Intestines/chemistry ; Intraepithelial Lymphocytes/physiology ; Limosilactobacillus fermentum/metabolism ; Male ; Mice ; Mucin-2/metabolism ; Mucin-4/metabolism ; T-Lymphocytes, Regulatory/physiology
مستخلص: Rationale: 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.
Objective: 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.
Methods and Results: 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 ( Bifidobacterium longum , Clostridium symbiosum , Faecalibacterium prausnitzii , and Lactobacillus fermentum ) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice.
Conclusions: 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.
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معلومات مُعتمدة: R01 NS094543 United States NS NINDS NIH HHS; TL1 TR003169 United States TR NCATS NIH HHS; R01 NS103592 United States NS NINDS NIH HHS; UL1 TR003167 United States TR NCATS NIH HHS; P30 DK056338 United States DK NIDDK NIH HHS; R01 HL134838 United States HL NHLBI NIH HHS; RF1 AG058463 United States AG NIA NIH HHS; P30 CA125123 United States CA NCI NIH HHS; P30 CA125123 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: aging; fecal microbiota transplantation; gut microbiota; inflammation; metabolomics; middle cerebral artery occlusion
المشرفين على المادة: 0 (Fatty Acids, Volatile)
0 (Interleukin-17)
0 (Muc2 protein, mouse)
0 (Muc4 protein, mouse)
0 (Mucin-2)
0 (Mucin-4)
تواريخ الأحداث: Date Created: 20200502 Date Completed: 20210521 Latest Revision: 20221207
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7415518
DOI: 10.1161/CIRCRESAHA.119.316448
PMID: 32354259
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4571
DOI:10.1161/CIRCRESAHA.119.316448