TY - JOUR
T1 - Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case–Control Study
AU - Haak, Bastiaan W.
AU - Westendorp, Willeke F.
AU - van Engelen, Tjitske S. R.
AU - Brands, Xanthe
AU - Brouwer, Matthijs C.
AU - Vermeij, Jan-Dirk
AU - Hugenholtz, Floor
AU - Verhoeven, Aswin
AU - Derks, Rico J.
AU - Giera, Martin
AU - Nederkoorn, Paul J.
AU - de Vos, Willem M.
AU - van de Beek, Diederik
AU - Wiersinga, W. Joost
N1 - Funding Information: We thank Rosan van der Lee and Jorn Hartman for their work in the microbiota sequencing preparations and Mark Davids for his aid in pre-processing the sequences. The centers and investigators participating in the Preventive Antibiotics in Stroke Study are listed in the SI Appendix. Funding Information: This trial was funded by The Netherlands Organization for Health Research and Development (grant no. 171002302 to DvdB and PJN; grant no. 016116358 to DvdB), The Netherlands Heart Foundation (grant no. 2009B095 to DvdB and PJN), the European Research Council (ERC Starting Grant to DvdB), and the Netherlands Organization for Scientific Research (VIDI grant number 91716475 to WJW and Spinoza award to WMdV). Acknowledgments Publisher Copyright: © 2020, The Author(s).
PY - 2021/8
Y1 - 2021/8
N2 - In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case–control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67–75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62–80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon p < 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77, p = 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.
AB - In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case–control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67–75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62–80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon p < 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77, p = 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.
KW - Butyrate
KW - Microbiome
KW - Stroke
KW - Trimethylamine-N-oxide
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85092566362&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33052545
U2 - https://doi.org/10.1007/s12975-020-00863-4
DO - https://doi.org/10.1007/s12975-020-00863-4
M3 - Article
C2 - 33052545
SN - 1868-4483
VL - 12
SP - 581
EP - 592
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 4
ER -