Gut Microbiota and Amino Acid Metabolism in Post-CPB Delayed Neurocognitive Recovery

November 8, 2026 updated by: XiaoLiang Wang

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Adult patients (aged 18 years or older) admitted to Nanjing First Hospital for elective cardiac surgery requiring cardiopulmonary bypass (CPB).

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: COHORT
  • Time Perspectives: PROSPECTIVE

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Other: Longitudinal Biospecimen Collection and Cognitive Assessment

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Global Cognitive Composite Z-Score (Delta-Z)
Time Frame: 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)
Time Frame: 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)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Fecal Metagenomic Taxonomic and Functional Profiles
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

XiaoLiang Wang

Investigators

  • Study Director: Xiaoliang Wang, The First Affiliated Hospital with Nanjing Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 22, 2026

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

November 8, 2026

First Submitted That Met QC Criteria

November 8, 2026

First Posted (Actual)

November 13, 2026

Study Record Updates

Last Update Posted (Actual)

November 13, 2026

Last Update Submitted That Met QC Criteria

November 8, 2026

Last Verified

November 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • KY20190404-03-KS-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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