Gut Microbiota and Amino Acid Metabolism in Post-CPB Delayed Neurocognitive Recovery
Role of the Holdemanella Biformis-Related Amino Acid Metabolic Guild and Intestinal Barrier Injury in Cardiopulmonary Bypass-Associated Delayed Neurocognitive Recovery: A Prospective Observational Cohort Study
Delayed neurocognitive recovery (dNCR) is a common neurological complication in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Emerging evidence suggests that CPB-associated hypoperfusion and perioperative stress remodel the gut microbiome and impair intestinal barrier integrity, which may contribute to neuroinflammation and cognitive decline via the gut-brain axis. This prospective observational cohort study aims to investigate the longitudinal trajectories of the gut metagenome (specifically focusing on Holdemanella biformis and amino acid metabolic functions), fecal and plasma metabolites (L-lysine, L-tryptophan, tryptophanol, and short-chain fatty acids), and plasma markers of intestinal barrier injury (I-FABP) and endotoxin response (LBP) from pre-operation (T0) to post-operation (T2) in adult CPB patients, and to evaluate their associations with postoperative dNCR and domain-specific cognitive changes.
Przegląd badań
Status
Warunki
Interwencja / Leczenie
Szczegółowy opis
Adult patients (aged 18 years or older) scheduled for elective cardiac surgery under cardiopulmonary bypass (CPB) will be prospectively enrolled. Comprehensive neuropsychological assessments covering global cognition (MoCA), learning and memory (HVLT or RAVLT), executive function (Trail Making Test B), and attention/processing speed (Digit Span and Digit Symbol tests) will be conducted at baseline (T0: 1 to 3 days before surgery) and postoperatively (T2: 5 to 10 days after surgery or before hospital discharge). Postoperative delirium will be screened daily using CAM or CAM-ICU. Paired stool and blood samples will be collected at both T0 and T2. Stool samples will undergo shotgun metagenomic sequencing and targeted metabolomics profiling (pre-specified panel: L-lysine, L-tryptophan, tryptophanol, acetate, propionate, and butyrate). Blood samples will be analyzed for intestinal fatty acid-binding protein (I-FABP) and lipopolysaccharide-binding protein (LBP). Linear mixed-effects models and multivariable regression adjusting for age and clinical covariates will be applied to identify time-by-dNCR interaction effects and associations with the continuous global cognitive composite delta-Z score.
Typ studiów
Zapisy (Szacowany)
Kontakty i lokalizacje
Kontakt w sprawie studiów
- Nazwa: Xiaoliang Wang
- Numer telefonu: 13776615743
- E-mail: wxl145381@njmu.edu.cn
Kopia zapasowa kontaktu do badania
- Nazwa: Feier Chen
- Numer telefonu: 18155529314
- E-mail: Liberate0109@outlook.com
Lokalizacje studiów
-
-
Jiangsu
-
Nanjing, Jiangsu, Chiny, 210006
- Rekrutacyjny
- Nanjing First Hospital
-
Kontakt:
- Xiaoliang Wang
- Numer telefonu: 13776615743
- E-mail: wxl145381@njmu.edu.cn
-
Kontakt:
- Feier Chen
- Numer telefonu: 18155529314
- E-mail: Liberate0109@outlook.com
-
-
Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Metoda próbkowania
Badana populacja
Adult patients (aged 18 years or older) admitted to Nanjing First Hospital for elective cardiac surgery requiring cardiopulmonary bypass (CPB).
Opis
Inclusion Criteria:
- (1) Aged 18 years or older; (2) Scheduled for elective cardiac surgery under cardiopulmonary bypass (CPB); (3) Able to complete Chinese neurocognitive assessments at baseline; (4) Able to provide a baseline stool sample at T0 (1 to 3 days before surgery); (5) Signed informed consent obtained.
Exclusion Criteria:
- (1) Preoperative delirium; (2) Inability to complete baseline neurocognitive assessments (e.g., severe visual, auditory, or language impairment); (3) Active gastrointestinal infection or inflammatory bowel disease (IBD); (4) History of recent fecal microbiota transplantation (FMT); (5) Severe pre-existing neurological or psychiatric disorders (e.g., dementia, stroke with severe sequelae, schizophrenia).
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Modele obserwacyjne: COHORT
- Perspektywy czasowe: PROSPECTIVE
Kohorty i interwencje
Grupa / Kohorta |
Interwencja / Leczenie |
|---|---|
|
Adult CPB Cohort
Adult patients aged 18 years or older undergoing elective cardiac surgery with cardiopulmonary bypass (CPB), evaluated longitudinally at T0 (1-3 days preoperatively) and T2 (5-10 days postoperatively or before discharge) for cognitive function, gut microbiome, fecal metabolites, and plasma intestinal injury biomarkers. |
Observational collection of paired stool and blood samples and administration of neuropsychological test batteries at T0 and T2 during routine perioperative care for cardiac surgery with CPB. No experimental therapeutic intervention is administered. |
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Change in Global Cognitive Composite Z-Score (Delta-Z)
Ramy czasowe: Baseline (T0: 1 to 3 days before surgery) and Postoperative (T2: 5 to 10 days after surgery or prior to hospital discharge)
|
A composite cognitive Z-score calculated from a neuropsychological test battery assessing learning and memory (Hopkins Verbal Learning Test [HVLT] or Rey Auditory Verbal Learning Test [RAVLT]), executive function (Trail Making Test Part B [TMT-B]), and attention/processing speed (Digit Span and Digit Symbol tests). Individual test change scores (T2 minus T0) are standardized and combined into a global cognitive composite delta-Z score (higher values indicate better cognitive preservation). |
Baseline (T0: 1 to 3 days before surgery) and Postoperative (T2: 5 to 10 days after surgery or prior to hospital discharge)
|
|
Incidence of Delayed Neurocognitive Recovery (dNCR)
Ramy czasowe: From baseline (T0: 1 to 3 days before surgery) to T2 (5 to 10 days after surgery or prior to hospital discharge)
|
Proportion of participants classified as having delayed neurocognitive recovery (dNCR) at T2 based on the reliable change index / pre-specified Z-score decline rules across the neuropsychological battery and Montreal Cognitive Assessment (MoCA). |
From baseline (T0: 1 to 3 days before surgery) to T2 (5 to 10 days after surgery or prior to hospital discharge)
|
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Changes in Fecal Metagenomic Taxonomic and Functional Profiles
Ramy czasowe: Baseline (T0: 1 to 3 days before surgery) and Postoperative (T2: 5 to 10 days after surgery or prior to hospital discharge)
|
Longitudinal changes in gut microbial community structure, specifically the relative abundance, prevalence, and strain markers of Holdemanella biformis, and KEGG Orthology (KO)/MetaCyc functional modules related to lysine, tryptophan, phosphotransferase system (PTS), and short-chain fatty acid (SCFA) metabolism. |
Baseline (T0: 1 to 3 days before surgery) and Postoperative (T2: 5 to 10 days after surgery or prior to hospital discharge)
|
|
Changes in Fecal Targeted Amino Acid Metabolites and Short-Chain Fatty Acids (SCFAs)
Ramy czasowe: Baseline (T0: 1 to 3 days before surgery) and Postoperative (T2: 5 to 10 days after surgery or prior to hospital discharge)
|
Concentrations of pre-registered fecal metabolites including L-lysine, L-tryptophan, tryptophanol, acetate, propionate, and butyrate quantified at T0 and T2. |
Baseline (T0: 1 to 3 days before surgery) and Postoperative (T2: 5 to 10 days after surgery or prior to hospital discharge)
|
|
Changes in Plasma Intestinal Fatty Acid-Binding Protein (I-FABP) and Lipopolysaccharide-Binding Protein (LBP)
Ramy czasowe: Baseline (T0: 1 to 3 days before surgery) and Postoperative (T2: 5 to 10 days after surgery or prior to hospital discharge)
|
Blood levels of I-FABP (marker of intestinal epithelial injury) and LBP (marker of host endotoxin response) measured by ELISA. |
Baseline (T0: 1 to 3 days before surgery) and Postoperative (T2: 5 to 10 days after surgery or prior to hospital discharge)
|
|
Incidence of Postoperative Delirium (POD)
Ramy czasowe: Postoperative Day 1 through Postoperative Day 7 (or hospital discharge)
|
Assessed daily after surgery using the Confusion Assessment Method (CAM) or CAM for the Intensive Care Unit (CAM-ICU). |
Postoperative Day 1 through Postoperative Day 7 (or hospital discharge)
|
Współpracownicy i badacze
Sponsor
Śledczy
- Dyrektor Studium: Xiaoliang Wang, The First Affiliated Hospital with Nanjing Medical University
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Zakończenie podstawowe (Szacowany)
Ukończenie studiów (Szacowany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Inne numery identyfikacyjne badania
- KY20190404-03-KS-01
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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