Short Chain Fatty Acids Taken at Time of Thrombectomy in Acute Ischemic Stroke Patients Are Independent of Stroke Severity But Associated With Inflammatory Markers and Worse Symptoms at Discharge

Nicholas Henry, Jacqueline Frank, Christopher McLouth, Amanda L. Trout, Andrew Morris, Jianzhong Chen, Ann M. Stowe, Justin F. Fraser, Keith Pennypacker

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Introduction: Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks. Methods: The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma via chemical derivatization UHPLC coupled tandem mass spectrometry using electrospray ionization and multiple reaction monitoring. Proteomic levels for 184 cardioembolic and inflammatory proteins was quantified from systemic and intracranial plasma by Olink. Arterial blood from cerebrovascular patients undergoing elective neurointerventional procedures was used as controls. Results: Acetate positively correlated with time from last known normal (LKN) and was significantly lower in stroke patients compared to control. Isobutyrate, Butyrate and 2-Methylbutyrate negatively correlated with %ΔNIHSS. Isobutyrate and 2-Methylbutyrate positively correlated with NIHSS discharge. SCFA concentrations were not associated with NIHSS admission, infarct volume, or edema volume. Multiple SCFAs positively associated with systemic and pro-inflammatory cytokines, most notably IL-6, TNF-α, VCAM1, IL-17, and MCP-1. Conclusions: Plasma SCFA concentrations taken at time of stroke are not associated with stroke severity at presentation. However, higher levels of SCFAs at the time of stroke are associated with increased markers of inflammation, less recovery from admission to discharge, and worse symptom burden at discharge.

Original languageEnglish
Article number797302
JournalFrontiers in Immunology
Volume12
DOIs
StatePublished - Jan 19 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Henry, Frank, McLouth, Trout, Morris, Chen, Stowe, Fraser and Pennypacker.

Keywords

  • brain ischemia
  • cytokine - immunological terms
  • inflammation
  • microbiome & dysbiosis
  • neuroimmunology of the gut

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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