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Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids after Traumatic Brain Injury and Impact on Neurologic Outcome.
J Neurotrauma. 2021 09 15; 38(18):2610-2621.JN

Abstract

Traumatic brain injury (TBI) alters microbial populations present in the gut, which may impact healing and tissue recovery. However, the duration and impact of these changes on outcome from TBI are unknown. Short-chain fatty acids (SCFAs), produced by bacterial fermentation of dietary fiber, are important signaling molecules in the microbiota gut-brain axis. We hypothesized that TBI would lead to a sustained reduction in SCFA producing bacteria, fecal SCFAs concentration, and administration of soluble SCFAs would improve functional outcome after TBI. Adult mice (n = 10) had the controlled cortical impact (CCI) model of TBI performed (6 m/sec, 2-mm depth, 50-msec dwell). Stool samples were collected serially until 28 days after CCI and analyzed for SCFA concentration by high-performance liquid chromatography-mass spectrometry/mass spectrometry and microbiome analyzed by 16S gene sequencing. In a separate experiment, mice (n = 10/group) were randomized 2 weeks before CCI to standard drinking water or water supplemented with the SCFAs acetate (67.5 mM), propionate (25.9 mM), and butyrate (40 mM). Morris water maze performance was assessed on post-injury Days 14-19. Alpha diversity remained stable until 72 h, at which point a decline in diversity was observed without recovery out to 28 days. The taxonomic composition of post-TBI fecal samples demonstrated depletion of bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae families, and enrichment of bacteria from the Verrucomicrobiaceae family. Analysis from paired fecal samples revealed a reduction in total SCFAs at 24 h and 28 days after TBI. Acetate, the most abundant SCFA detected in the fecal samples, was reduced at 7 days and 28 days after TBI. SCFA administration improved spatial learning after TBI versus standard drinking water. In conclusion, TBI is associated with reduced richness and diversity of commensal microbiota in the gut and a reduction in SCFAs detected in stool. Supplementation of soluble SCFAs improves spatial learning after TBI.

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Authors+Show Affiliations

Opeyemi OM
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Rogers MB
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Firek BA
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Janesko-Feldman K
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Vagni V
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Mullett SJ
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Wendell SG
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Nelson BP
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
New LA
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Mariño E
Department of Biochemistry, Monash University, Melbourne, Victoria, Australia.
Kochanek PM
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. UPMC Children's Hospital of Pittsburgh Neuroscience Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bayır H
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. UPMC Children's Hospital of Pittsburgh Neuroscience Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Clark RSB
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. UPMC Children's Hospital of Pittsburgh Neuroscience Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Morowitz MJ
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Center for Microbiome and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Simon DW
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. UPMC Children's Hospital of Pittsburgh Neuroscience Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

MeSH

AnimalsBrain Injuries, TraumaticBrain-Gut AxisDietary SupplementsDysbiosisFatty Acids, VolatileFecesGastrointestinal MicrobiomeMaleMaze LearningMiceMice, Inbred C57BLNervous System DiseasesPsychomotor PerformanceRNA, Ribosomal, 16STreatment Outcome

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33957773

Citation

Opeyemi, Oluwasinmisola M., et al. "Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids After Traumatic Brain Injury and Impact On Neurologic Outcome." Journal of Neurotrauma, vol. 38, no. 18, 2021, pp. 2610-2621.
Opeyemi OM, Rogers MB, Firek BA, et al. Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids after Traumatic Brain Injury and Impact on Neurologic Outcome. J Neurotrauma. 2021;38(18):2610-2621.
Opeyemi, O. M., Rogers, M. B., Firek, B. A., Janesko-Feldman, K., Vagni, V., Mullett, S. J., Wendell, S. G., Nelson, B. P., New, L. A., Mariño, E., Kochanek, P. M., Bayır, H., Clark, R. S. B., Morowitz, M. J., & Simon, D. W. (2021). Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids after Traumatic Brain Injury and Impact on Neurologic Outcome. Journal of Neurotrauma, 38(18), 2610-2621. https://doi.org/10.1089/neu.2020.7506
Opeyemi OM, et al. Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids After Traumatic Brain Injury and Impact On Neurologic Outcome. J Neurotrauma. 2021 09 15;38(18):2610-2621. PubMed PMID: 33957773.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids after Traumatic Brain Injury and Impact on Neurologic Outcome. AU - Opeyemi,Oluwasinmisola M, AU - Rogers,Matthew B, AU - Firek,Brian A, AU - Janesko-Feldman,Keri, AU - Vagni,Vincent, AU - Mullett,Steven J, AU - Wendell,Stacy G, AU - Nelson,Brittany P, AU - New,Lee Ann, AU - Mariño,Eliana, AU - Kochanek,Patrick M, AU - Bayır,Hülya, AU - Clark,Robert S B, AU - Morowitz,Michael J, AU - Simon,Dennis W, Y1 - 2021/06/07/ PY - 2021/5/8/pubmed PY - 2022/2/22/medline PY - 2021/5/7/entrez KW - gut–brain axis KW - microbiome KW - short-chain fatty acids KW - traumatic brain injury SP - 2610 EP - 2621 JF - Journal of neurotrauma JO - J Neurotrauma VL - 38 IS - 18 N2 - Traumatic brain injury (TBI) alters microbial populations present in the gut, which may impact healing and tissue recovery. However, the duration and impact of these changes on outcome from TBI are unknown. Short-chain fatty acids (SCFAs), produced by bacterial fermentation of dietary fiber, are important signaling molecules in the microbiota gut-brain axis. We hypothesized that TBI would lead to a sustained reduction in SCFA producing bacteria, fecal SCFAs concentration, and administration of soluble SCFAs would improve functional outcome after TBI. Adult mice (n = 10) had the controlled cortical impact (CCI) model of TBI performed (6 m/sec, 2-mm depth, 50-msec dwell). Stool samples were collected serially until 28 days after CCI and analyzed for SCFA concentration by high-performance liquid chromatography-mass spectrometry/mass spectrometry and microbiome analyzed by 16S gene sequencing. In a separate experiment, mice (n = 10/group) were randomized 2 weeks before CCI to standard drinking water or water supplemented with the SCFAs acetate (67.5 mM), propionate (25.9 mM), and butyrate (40 mM). Morris water maze performance was assessed on post-injury Days 14-19. Alpha diversity remained stable until 72 h, at which point a decline in diversity was observed without recovery out to 28 days. The taxonomic composition of post-TBI fecal samples demonstrated depletion of bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae families, and enrichment of bacteria from the Verrucomicrobiaceae family. Analysis from paired fecal samples revealed a reduction in total SCFAs at 24 h and 28 days after TBI. Acetate, the most abundant SCFA detected in the fecal samples, was reduced at 7 days and 28 days after TBI. SCFA administration improved spatial learning after TBI versus standard drinking water. In conclusion, TBI is associated with reduced richness and diversity of commensal microbiota in the gut and a reduction in SCFAs detected in stool. Supplementation of soluble SCFAs improves spatial learning after TBI. SN - 1557-9042 UR - https://www.unboundmedicine.com/medline/citation/33957773/Sustained_Dysbiosis_and_Decreased_Fecal_Short_Chain_Fatty_Acids_after_Traumatic_Brain_Injury_and_Impact_on_Neurologic_Outcome_ DB - PRIME DP - Unbound Medicine ER -