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The Effect of Probiotics on Systemic Inflammation and Metabolic Endotoxemia in Patients Undergoing Bariatric Surgery

Not Applicable
Conditions
Bariatric Surgery Candidate
Dysbiosis
Interventions
Dietary Supplement: placebo
Dietary Supplement: probiotic supplementation
Registration Number
NCT05407090
Lead Sponsor
Medical University of Gdansk
Brief Summary

This study explores the effects of probiotic administration on the outcomes of surgical treatment, and also on the state of the intestinal microbiota and the intestinal barrier. The study protocol is designed as a randomized double-blind placebo-controlled clinical trial. Patients qualified for bariatric surgery will be randomized to receive probiotics or a placebo for 12 weeks. Researchers are going to evaluate changes in intestinal microbiota, epithelial permeability, weight loss, postoperative complications, and serum parameters reflecting inflammation, metabolic profile, and metabolic endotoxemia.

Detailed Description

The study is designed as a randomized double-blind placebo-controlled clinical trial with a 12-week probiotics intervention period. Eighty patients qualified for one of 3 types of bariatric surgery Roux-en-Y Gastric Bypass (RYGB), One-Anastomosis Gastric Bypass (OAGB), Laparoscopic Sleeve Gastrectomy (LSG) will be randomized to receive probiotics or a placebo. The time frame for the study is 6 months before and 6 months after surgery.

During this time, it is planned to collect stool samples at 5-time points: before the start of the study, before the introduction of probiotic therapy, 2 weeks before the operation, and 3 and 6 months after the operation. Collected fecal samples will be subjected to quantitative and qualitative content of the intestinal microbiota using the new generation sequencing method, as well as intestinal permeability parameters such as I-FABP (Intestinal fatty acid-binding protein), bacterial short-chain fatty acids (SCFA), and lipopolysaccharide (LPS).

Simultaneously with the collection of stool samples, an assessment of the patient's nutrition will be performed using the food frequency questionnaire (FFQ) and three-day dietary recall.

The blood samples will be collected at 4-time points: before the start of the study, before the operation, and 3 and 6 months after the operation. The following parameters will be marked in the collected blood samples: glucose, insulin, HbA1c, liver tests: ALT (Alanine transaminase), AST (Aspartate transaminase), GGTP (Gamma-glutamyl Transferase), alkaline phosphatase (ALP), bilirubin; lipid profile, CRP (C-reactive protein), total protein, albumin, inflammatory markers: IL-6, IL-10, Tumor necrosis factor-α (TNF-α), IL-8, IL-R2.

During the examination, tissue samples will be taken at 2-time points. The first is during routine gastroscopy before surgery. Gastroscopy will be performed before the inclusion of the probiotic. Duodenal and stomach biopsy will be performed during gastroscopy. The second time tissue samples will be collected intraoperatively. Gastric specimens will be collected from patients undergoing LSG. Patients qualified for RYGB and OAGB surgery will undergo gastric and jejunum biopsy. The parameters of the intestinal barrier status will be assessed in the collected tissues: Plasmalemma Vesicle-Associated Protein-1 (PLVAP-1), and Regenerating Islet Derived Protein 3 Alpha (Reg3α).

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
80
Inclusion Criteria
  • qualification for LSG, RYGB, OAGB bariatric surgery
  • age over 18
  • written consent to participate in the study
Exclusion Criteria
  • allergy/intolerance to any of the ingredients of the preparations,
  • inflammatory bowel diseases,
  • current antibiotic therapy,
  • immunosuppression,
  • biological treatment,
  • long-term antibiotic therapy,
  • taking probiotics in the 1 month prior to study enrollment,
  • neurodegenerative diseases.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboplaceboPatients will take 4 capsules of a placebo preparation daily.
Probioticprobiotic supplementationPatients will take 4 capsules of a multi-strain probiotic preparation daily. Product characteristics: 1 capsule of the preparation contains ≥2.5 x 10\^9 CFU / g of live bacteria (Bifidobacterium lactis W52, Lactobacillus brevis W63, Lactobacillus casei W56, Lactococcus lactis W19, Lactococcus lactis W58, Lactobacillus acidophilus W37, Bifidobacterium bifidillum W23)
Primary Outcome Measures
NameTimeMethod
Evaluation of changes in inflammation statusbefore the intervention, 3 and 6 months after surgery

The inflammation will be assessed by measuring CRP concentration in the serum

Evaluation of changes in weight loss of the body3 and 6 months after surgery

Weight loss will be measured and expressed in kilograms

Secondary Outcome Measures
NameTimeMethod
Evaluation of changes in endotoxemiabefore the intervention, 3 and 6 months after surgery

Endotoxemia will be assessed by measuring lipopolysaccharide in serum.

Evaluation of changes in nutrition - quality and quantitytwo weeks before surgery and 3 months after surgery

The assessment of the nutrition will be performed using a 3-day food record

Evaluation of changes in the state of the intestinal microbiota - the content of intestinal microbiotabefore the intervention, 2 weeks before surgery, 3 and 6 months after surgery

The state of the intestinal microbiota will be measured by quantitative and qualitative content of the intestinal microbiota using the new generation sequencing method (16s rRNA)

Evaluation of changes in the state of the intestinal microbiota - the content of bacterial metabolites short-chain fatty acids (SCFA)before intervention, 2 weeks before surgery, 3 and 6 months after surgery

The state of the intestinal microbiota will be measured by the quantitative and qualitative content of bacterial metabolites - short-chain fatty acids (SCFA)

Evaluation of changes in the permeability of the intestinal barrierbefore the intervention, 2 weeks before surgery, 3 and 6 months after surgery

The permeability of the intestinal barrier will be measured by the presence of increased intestinal permeability parameter - I-FABP in stool

Evaluation of changes in the state of the intestinal barrierbefore the intervention, in time of surgery

The permeability of the intestinal barrier will be measured by the concentration of PLVAP-1 and Reg3-alfa in collected tissues

Evaluation of changes in inflammation profile in serumbefore the intervention, 3 and 6 months after surgery

The inflammation profile will be assessed by a concentration of cytokines (IL-6, TNF-alfa, IL-10, IL-8, IL-2R) in the serum.

Evaluation of changes in intestine inflammationbefore the intervention, 3 and 6 months after surgery

The intestine inflammation will be measured by the level of calprotectin in the stool

Evaluation of changes in nutrition - frequencybefore the intervention and 6 months after surgery

The assessment of the nutrition will be performed using the food frequency questionnaire (FFQ)

Postoperative complicationsDuring six months after surgery

Postoperative complications will be assessed by the Clavien-Dindo classification of surgical complications (on a scale of 1 to 5, the higher the result, the more intensive treatment is required for the described complication)

Trial Locations

Locations (1)

Medical University of Gdańsk

🇵🇱

Gdańsk, Pomeranian, Poland

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