Post-operative Ileus and Gut Microbiota

Post-operative Ileus of Colorectal Cancer Patients Associated With Perioperative Gut Microbiota

Postoperative ileus (POI) is a common clinical condition after abdominal surgical procedure, leading to increased patient morbidity and prolonged hospitalisation.The mechanism of POI is not very clear until now. At the end of the 20th century, the inflammatory-mediated ileus hypothesis was introduced. But the initial trigger of the inflammatory cascade is unclear.Previous study demonstrate a clear association between colonic transit time, gut microbiota composition and urinary metabolic phenotype. Here the investigators suggest that the perioperative gut microbiota may contribute to POI.

Study Overview

• Status: Unknown
• Conditions: Post-operative Ileus
• Intervention / Treatment: Other: Fecal and blood samples collection for analysis

Detailed Description

Postoperative ileus (POI) is a common clinical condition after abdominal surgical procedure, leading to increased patient morbidity and prolonged hospitalisation.

The clinical manifestations include abdominal distension, nausea, vomiting and the inability to pass stools or tolerate a solid diet. In addition to the discomfort experienced by patients, postoperative ileus is also an important risk factor for complications such as wound dehiscence and pulmonary and thromboembolic complications. Ileus was found to be an important predictor of extended postoperative hospital stays and costs in patients undergoing colectomy.

The mechanism of POI is not very clear until now. At the end of the 20th century, the inflammatory-mediated ileus hypothesis was introduced. But the initial trigger of the inflammatory cascade is unclear The innate immune system recognises two large classes of macromolecules: first, those related to pathogens or pathogen-associated molecular patterns (PAMPs), and secondly, molecules released in response to cell damage or damage-associated molecular patterns (DAMPs). The prototype of PAMPs is lipopolysaccharide (LPS), a constituent of the Gram-negative bacterial cell wall. Translocation of microbial products into the intestinal tissue is a well-documented feature in POI. Previous study demonstrate a clear association between colonic transit time, gut microbiota composition and urinary metabolic phenotype. Here the investigators suggest that the perioperative microbiome may contribute to POI. This study apply NGS(next generation sequencing) technique to analyse the composition of the perioperative gut microbiota of CRC(colorectal cancer) patients, then analysis the relationship between the dynamic variation of gut microbiota and POI.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Yunwei Wei, professor; Phone Number: +86045185553099; Email: hydwyw11@hotmail.com
• Study Contact Backup: Name: Yang Liu, assistant research fellow; Phone Number: +8618345180169; Email: lyang712@icloud.com

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Recruiting
      • First Affiliated Hospital of Harbin Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study participants are patients need undergo an exhaustive colorectal cancer surgical resection in the First Affiliated Hospital of Harbin Medical University from May 1, 2018 to Dec 31, 2019.

Description

Inclusion Criteria:

• Requirements of informed consent and assent of participant, parent or legal guardian as applicable
• Patients with colorectal cancer scheduled for radical coloproctectomy and between the age of 35 and 80 years old without considering sex.
• Patients with BMI= 18.5-23.9

Exclusion Criteria:

• Patients with colorectal cancer with distant metastasis
• Chronic renal diseases and hepatic cirrhosis
• Chronic ischemic heart disease with unstable angina, chronic heart failure at class III or IV and acute myocardial infarction in the last 6 months
• Individuals with a history of Chronic diarrhea
• Individuals with a history of Diabetes mellitus
• Individuals with a history of Hypertension
• Individuals with a history of autoimmune diseases
• Use of antibiotics and probiotics 3 mouth before samples collection
• Individuals with a history of abdominal operation due to any reason
• Individuals with any history of cancer other than colorectal cancer
• Individuals with Inflammatory bowel disease

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Delayed transit; CRC patients with delayed gut transit recovery( first time defecation >3 day )	Other: Fecal and blood samples collection for analysis; Fecal sample analysis will consist of the following procedure : Microbial DNA extraction, amplicon library construction, sequencing and analysis; Clustering "MiSeq" reads into operational taxonomic units (OTUs).
Normal transit; CRC patients with normal gut transit recovery( first time defecation <=3 day )	Other: Fecal and blood samples collection for analysis; Fecal sample analysis will consist of the following procedure : Microbial DNA extraction, amplicon library construction, sequencing and analysis; Clustering "MiSeq" reads into operational taxonomic units (OTUs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gut microbiome dynamics in colorectal cancer patients during the perioperative period between two groups	The diversity, structure of fecal microbiota and relative abundance of special bacterial taxa 16S rRNA gene sequencing will be performed.	The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection)
The time ranging from operation day to the day of first defecation	The recovery of gut transit can be indicated by the first defecation	Up to 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of plasma i-FABP(intestinal fatty acid-binding protein)	The detection of i-FABP is useful to determine localized changes in intestinal damage.	The day before operation day, every day from first to fifth post-operative day
Concentration of plasma LPS	The presence of lipopolysaccharide (LPS) has been used as an indirect measurement of bacterial translocation and systemic exposure to bacteria.	The day before operation day, every day from first to fifth post-operative day
Concentration of fecal LPS	LPS was derived from gram-negative bacteria in the intestinal tract, and LPS in blood was derived from feces.	The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection)
Concentration of fecal calprotectin	Fecal calprotectin is not only an indicator of intestinal inflammation, but also an indicator of intestinal mucosal barrier.	The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection)

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Harbin Medical University
• Investigators: Study Director: Yunwei Wei, First Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): September 30, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: May 13, 2019
• First Submitted That Met QC Criteria: July 4, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): July 8, 2019
• Last Update Submitted That Met QC Criteria: July 4, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Gut Microbiota; perioperative period; Post-operative Ileus
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Obstruction; Ileus
• Other Study ID Numbers: Yunwei Wei 2019-04-19

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