Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child, Objectives: Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children. Design: Prospective multicenter cohort study. Setting: Three U.K.-based PICUs. Patients: Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55). Interventions: Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls. Measurements and Main Results: Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = –0.2; p = 0.037). Conclusions: Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Drs. Wijeyesekera and Wagner contributed equally. Dr. Wijeyesekera developed and supervised the metabolic profiling strategy, undertook data analysis, and wrote the article. Dr. Wagner developed and supervised the microbial profiling strategy, undertook data analysis, and wrote the article. Dr. De Goffau analyzed the microbial data and co-wrote the article. Ms. Thurston undertook sample processing and data analysis. Drs. Rodrigues Sabino and Zaher, Ms. White, Ms. Ridout, and Dr. Valla undertook sample processing, data collection, and analysis. Dr. Meyer undertook data analysis. Drs. Peters, Branco, Torok, Meyer, and Klein contributed to protocol development, supervised data analysis, and co-wrote the article. Dr. Parkhill developed the microbial profiling protocol, supervised all aspects of the microbial data analysis, and co-wrote the article. Drs. Frost and Holmes developed the metabolic profiling protocol, supervised all aspects of the metabolic data analysis, and co-wrote the article. Dr. Pathan conceived and supervised the study and wrote the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). 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), and a Levi-Montalcini award from the European Society of Intensive Care Medicine (to Dr. Pathan). 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. Dr. Rodrigues Sabino’s institution received funding from National Institute for Health Research Imperial Biomedical Research Centre Institute of Translational Medicine and Therapeutics Call for Experimental Medicine Proposals. Dr. Valla received funding from Baxter and Nutricia. Dr. Meyer received funding from academic lectures for Danone, Nestle and Mead Johnson, and from the Mead Johnson Allergy Advisory Board. Dr. Frost’s institution received funding from Nestle and Heptares, and he received support for article research from Research Councils UK and Bill & Melinda Gates Foundation. Drs. Frost, Parkhill, and Pathan received support for article research from Wellcome Trust/Charity Open Access Fund. Dr. Parkhill’s institution received funding from Wellcome Trust, and he received funding from Next Gen Diagnostics Llc. Dr. Pathan’s institution received funding from European Society of Intensive Care Medicine, Evelyn Trust, and Wellcome Trust. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Nazima Pathan, FRCPCH, PhD, Department of Paediatrics, University of Cambridge, Level 8, Addenbrookes Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom. E-mail: np409@cam.ac.uk Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
ΩτοΡινοΛαρυγγολόγος Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,
Translate
Ετικέτες
Κυριακή 14 Ιουλίου 2019
Αναρτήθηκε από
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
στις
2:51 π.μ.
Ετικέτες
00302841026182,
00306932607174,
alsfakia@gmail.com,
Anapafseos 5 Agios Nikolaos 72100 Crete Greece,
Medicine by Alexandros G. Sfakianakis
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Αρχειοθήκη ιστολογίου
-
►
2023
(278)
- ► Φεβρουαρίου (139)
- ► Ιανουαρίου (139)
-
►
2022
(1962)
- ► Δεκεμβρίου (107)
- ► Σεπτεμβρίου (158)
- ► Φεβρουαρίου (165)
- ► Ιανουαρίου (163)
-
►
2021
(3614)
- ► Δεκεμβρίου (152)
- ► Σεπτεμβρίου (271)
- ► Φεβρουαρίου (64)
- ► Ιανουαρίου (357)
-
►
2020
(3279)
- ► Δεκεμβρίου (396)
- ► Σεπτεμβρίου (157)
- ► Φεβρουαρίου (382)
- ► Ιανουαρίου (84)
-
▼
2019
(11718)
- ► Δεκεμβρίου (265)
- ► Σεπτεμβρίου (545)
-
▼
Ιουλίου
(1727)
- Viruses, Vol. 11, Pages 701: Metagenomic N...
- Vaccines, Vol. 7, Pages 77: Nanobodies that Neutr...
- Antibiotic and Pesticides Residues in Breast Milk
- Social Sciences, Vol. 8, Pages 229: The Street-Wi...
- Psych, Vol. 1, Pages 429-430: Expression of Conce...
- Microorganisms, Vol. 7, Pages 230: Contras...
- Medicina, Vol. 55, Pages 423: Handheld Ult...
- JCM, Vol. 8, Pages 1144: Shock Index Predi...
- Humanities, Vol. 8, Pages 130: The Composi...
- Children, Vol. 6, Pages 89: Emerging Topics in Ca...
- Cancers, Vol. 11, Pages 1091: Glioblastoma...
- Impact of skeletal muscle mass volume on surgica...
- A method using the cephalic vein for superdraina...
- Direct muscle neurotization with long acellular ...
- Allergy, Asthma , Immunology
- CranioMaxillofacial Surgery
- Neuroradiology/Head and Neck ImagingOriginal Res...
- Systems approach reveals photosensitivity and P...
- NeuroOncology
- Griseofulvin versus Terbinafine for pediatric Ti...
- Identification of Cryptococcus Antigen in HIV‐po...
- Epidemiology and Management Burden of Invasive F...
- Phaeohyphomycosis caused by Phialophora american...
- MicrosurgeryEarly View Online Version of Recor...
- Chondro-Osseous Respiratory Epithelial Adenoma...
- Otolaryngology
- Adult-Type Rhabdomyoma of the Omohyoid Muscle ...
- Thyroglossal Duct Cyst Carcinoma in a Young Fe...
- Case Reports in Otolaryngology Volume 2019, Arti...
- Lung Perfusion Scintigraphy in Eisenmenger Syndr...
- Case Reports in Otolaryngology
- Otology & Neurotology
- Hunger-Activated AgRP Neurons Inhibit MPOA Neur...
- Development of a delayed-release nutrient for appe...
- Neoadjuvant BRAF‐targeted therapy in regionally ...
- Discoidin domain receptors: A promising target i...
- Self-seeding circulating tumor cells promote th...
- Necrosis Rather Than Apoptosis is The Dominant f...
- Magician's Corner: How to Start Lear...
- Impact of Long Wavelength Ultraviolet A1 and Vis...
- Method for Measurements of Terrestrial Ultravio...
- Unusually complicated course of a common disease...
- Lead poisoning has been described in older childre...
- Teaching Topic Immediate Transfusion in Africa...
- INTERACTIVE MEDICAL CASE
- Weighing the Risks and Rewards of Peanut Oral...
- Buried bumper syndrome (BBS) is one of the uncommo...
- GASTROENTEROLOGY ENDOSCOPY: NOT JUST A PROCEDURA...
- Health Physics
- Techniques in Shoulder & Elbow Surgery
- Primer on Precision Medicine for Complex Chronic...
- Clinical and Translational Gastroenterology
- Technological Pedagogical and Content Knowledge ...
- Intraoperative Placement of Paravertebral Cathet...
- Heterogeneity of human pancreatic islet isolatio...
- Anaesthesia
- Academic Medicine
- Menopause
- Clinical Orthopaedics and Related Research(R)
- pH-sensitive anti-CTLA4 antibodies: yes to effi...
- Therapeutics
- American Journal of Therapeutics
- FULL MOON > AUGUST - We have the Algonquin Indians...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Pediatric Radiology
- Obesity Surgery
- Pediatric Orthopaedics
- Rheumatology
- Anaesthesiology
- Cardiovascular Medicine
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Trauma and Acute Care Surgery
- Cancer Research and Clinical Oncology
- Endocrine
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Hypertension
- Angiogenesis
- Musculoskeletal Surgery
- Physiological Sciences
- Cardiology
- Gastroenterology
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Update on treatment options for blast-induced he...
- Triglycerides and endothelial function: molecula...
- Neuropsychology as a Method of Diagnosis and Tre...
- Combination of laser microdissection, 2D-DIGE an...
- Plasma lipoproteome in Alzheimer’s disease: a p...
- Validation of a novel model for the early dete...
- Journal of the European Academy of Dermatology a...
- ► Φεβρουαρίου (1143)
- ► Ιανουαρίου (744)
-
►
2017
(2)
- ► Φεβρουαρίου (1)
- ► Ιανουαρίου (1)
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου