TY - JOUR
T1 - Profiling gut microbiota and bile acid metabolism in critically ill children
AU - Kean, Iain Robert Louis
AU - Wagner, Joseph
AU - Wijeyesekera, Anisha
AU - de Goffau, Marcus
AU - Thurston, Sarah
AU - Clark, John A.
AU - White, Deborah K.
AU - Ridout, Jenna
AU - Agrawal, Shruti
AU - Kayani, Riaz
AU - O’Donnell, Roddy
AU - Ramnarayan, Padmanabhan
AU - Peters, Mark J.
AU - Klein, Nigel
AU - Holmes, Elaine
AU - Parkhill, Julian
AU - Baker, Stephen
AU - Pathan, Nazima
N1 - Funding Information: This research/study/project was funded/supported by the NIHR Imperial Biomedical Research Centre (BRC). We would like to thank the children and families participating in the study, along with the clinicians treating them. We would like to thank Miss Esther Daubney RNC for her assistance with the archival data. We also thank the core informatics, sequencing, and pathogen informatics teams at the Wellcome Trust Sanger Institute. This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: Aspects of the work were funded by an Imperial College Biomedical Research Centre award (to Drs. Holmes and Pathan), the Evelyn Trust (to Drs. Parkhill and Pathan), a Wellcome Trust Core Informatics Award (to Dr. Parkhill), Great Ormond Street Hospital Children’s Charity (to Drs. Peters and Ramnarayan), a Wellcome Trust Fellowship (Dr. Baker 215515/Z/19/Z), a Levi-Montalcini award from the European Society of Intensive Care Medicine (to Dr. Pathan) and an Action For Medical Research UK award (Dr. Pathan GN2751). The research was supported by the National Institute for Health Research Biomedical Research Centres based at Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Great Ormond Street Hospital NHS Foundation Trust, Imperial College Healthcare NHS Trust, and Imperial College London. NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). Funding Information: The work in this study is supported by funding to NP from Action Medical Research, the Evelyn Trust and the European Society of Intensive Care Medicine. JP and SB received funding from The Wellcome Trust, and JP received funding from Next Gen Diagnostics Llc. The remaining authors have disclosed that they do not have any potential conflicts of interest. Funding Information: This research/study/project was funded/supported by the NIHR Imperial Biomedical Research Centre (BRC). We would like to thank the children and families participating in the study, along with the clinicians treating them. We would like to thank Miss Esther Daubney RNC for her assistance with the archival data. We also thank the core informatics, sequencing, and pathogen informatics teams at the Wellcome Trust Sanger Institute. This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of the Lachnospiraceae recovered during the late-acute phase (days 8–10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift in Lachnospiraceae. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids.
AB - Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of the Lachnospiraceae recovered during the late-acute phase (days 8–10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift in Lachnospiraceae. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids.
UR - http://www.scopus.com/inward/record.url?scp=85132299914&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-022-13640-0
DO - https://doi.org/10.1038/s41598-022-13640-0
M3 - Article
C2 - 35729169
SN - 2045-2322
VL - 12
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 10432
ER -