Impact of Probiotics on Gut Microbiome During Antibiotic Prophylaxis in Elective Orthopedic Surgery

Phase 4

Not yet recruiting

• Conditions: Dysbiosis; Gut -microbiota; Microbiome Analysis; Probiotic; Antibiotic Prophylaxis
• Interventions: Drug: Placebo Capsule; Dietary Supplement: Probiotic with Human Milk Oligosaccharides (HMO)

• Registration Number: NCT06791993
• Lead Sponsor: Acibadem Maslak Hospital

Brief Summary

This study aims to evaluate whether probiotics can help maintain a healthy gut microbiome in patients receiving prophylactic antibiotics during elective orthopedic surgery. Antibiotics, while effective in preventing infections, can disrupt the balance of gut bacteria, leading to dysbiosis. The study hypothesizes that the use of probiotics during the perioperative period can prevent or reduce this disruption, supporting gut health and overall well-being. The research seeks to answer whether combining probiotics with routine antibiotic prophylaxis can preserve gut microbiome balance and improve patient outcomes.

Detailed Description

This double-blinded, randomized controlled trial aims to evaluate the effect of probiotics on maintaining gut microbiome balance in patients undergoing elective orthopedic surgery who receive routine prophylactic antibiotics. Antibiotics, while essential for reducing the risk of surgical site infections, are known to disrupt gut microbiota, leading to dysbiosis, an imbalance in microbial composition. Dysbiosis can compromise gut health, reduce microbial diversity, and impair metabolic functions essential for recovery.

The study explores whether a dual-strain probiotic with Human Milk Oligosaccharides (HMO) can prevent or minimize dysbiosis during the perioperative period. By comparing patients receiving routine antibiotics alone with those receiving antibiotics plus probiotics, this trial seeks to identify if probiotics can preserve gut microbial diversity and function.

To assess the impact, fecal samples collected at specific time points will undergo detailed microbiome analysis, including metrics such as microbial richness, diversity, and such. Secondary measures will evaluate the broader effects on patient well-being during the recovery period.

This study is designed to provide evidence for the potential role of probiotics as an adjunct therapy to maintain gut health during antibiotic use, offering a novel approach to improving post-surgical recovery and patient outcomes.

Study Timeline

• Study First Submitted: 2024-12-23
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-18
• Last Update Submitted: 2025-01-18
• Study First Posted: 2025-01-24
• Last Update Posted: 2025-01-24
• Study Start: 2025-02-01
• Primary Completion: 2025-08-01
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Adults aged between 18 and 65 years
• Scheduled for elective low-risk orthopedic surgery (carpal tunnel release, A1 pulley release, knee arthroscopic surgery).

Exclusion Criteria

• History of infection or antibiotic use within the last 12 weeks.
• Use of routine probiotics, vitamins, or herbal supplements in the last 4 weeks.
• Known allergy to beta-lactam or cephalosporin antibiotics.
• History of autoimmune disease, uncontrolled systemic disease, or chronic inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis).
• History of chronic intestinal diseases such as small intestine bacterial overgrowth (SIBO), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), or celiac disease.
• Increased risk of infection due to medical comorbidities or use of immunosuppressive drugs.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Routine Antibiotic Prophylaxis + Placebo	Placebo Capsule	This arm receives routine antibiotic prophylaxis with a single dose of intravenous Cefazolin and a placebo capsule to match the probiotic intervention.
Routine Antibiotic Prophylaxis + Probiotics	Probiotic with Human Milk Oligosaccharides (HMO)	This arm receives routine antibiotic prophylaxis with a single dose of intravenous Cefazolin and a dual-strain probiotic containing Human Milk Oligosaccharides (HMO).

Primary Outcome Measures

Name	Time	Method
Maintenance of Gut Microbiome Balance	2 weeks preoperatively (T0) to 1 month postoperatively (T4).	Evaluate whether probiotic administration preserves gut microbiome balance during the perioperative period by assessing changes in microbial richness, diversity, and evenness. Shotgun metagenomic sequencing analysis will be used to measure microbial composition and diversity.

Secondary Outcome Measures

Name	Time	Method
Microbiome health index ( MHI) OR Microbiome health index for post-antiobiotic (MHI- A)	2 weeks preoperatively (T0) to 1 month postoperatively (T4).	Microbiome Health Index (MHI-A) calculated via microbiome analysis. MHI-A is a biomarker and a quantitative measure method of post-antibiotic dysbiosis and subsequent restoration. Higher MHI-A means higher healthy microbiome with low antibiotic resistance gene. Lower MHI- A mean dysbiosis, high antiobiotic resistance gene
WHO-5 Well-being Index	1 week preoperatively (T1) and 2 weeks postoperatively (T3).	The WHO-5 Well-Being Index (The World Health Organization-Five Well-Being Index) is a self-report instrument measuring mental well-being. It consists of five statements relating to the past two weeks. Each statement is rated on a 6-point scale (0,1,2,3,4,5), with higher scores indicating better mental well-being.; The raw score is calculated by totalling the scores on each of the five questions. Theraw score ranges from zero to 25, zero representing worst possible mental well-beingand 25 representing best possible mental well-being. To get a percentage score ranging from zero to 100, the raw score is multiplied by four.; A percentage score of zero represents worst possible mental well-being; a score of 100 represents best possible mental well-being
Dysbiosis Index	2 weeks preoperatively (T0) to 1 month postoperatively (T4).	Dysbiosis Index is the ratio of the total number of Proteobacteria strains divided by total overall bacteria strain
Firmicutes/Bacteroidetes Ratio	2 weeks preoperatively (T0) to 1 month postoperatively (T4).	Determine changes in the Firmicutes/Bacteroidetes ratio, a key marker of dysbiosis, between intervention groups. Using shotgun metagenomic sequencing.
Short-Chain Fatty Acid (SCFA) Production	2 weeks preoperatively (T0) to 1 month postoperatively (T4).	Assess changes in SCFA production (e.g., acetate, butyrate) as indicators of gut health and microbiome function. Using SCFA quantification through microbiome metabolite analysis.
EuroQol 5-Dimension (EQ-5D) score.	1 week preoperatively (T1) and 2 weeks postoperatively (T3).	EuroQol 5-Dimension (EQ-5D) score (EQ-5D) descriptive system comprises the same five dimensions (MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN / DISCOMFORT and ANXIETY / DEPRESSION), beach dimension having five response levels:no problems, slight problems, moderateproblems, severe problems, unable to/extreme problems. The respondent is asked to indicate his/her health state by checking the box next to the most appropriate response level for each of the five dimensions. Responses are coded as single-digit numbers expressing the severity level selected in each dimension. For instance, 'slight problems' (e.g. 'I have slight problems in walking about') is always coded as '2'. The digits for the five dimensions can be combined in a 5-digit code that describes the respondent's health state; for instance, 21111 means slight problems in the mobility dimension and no problems in any of the other dimensions

Trial Locations

Locations (6)

Parvizi Surgical Innovation; 🇺🇸 Philadelphia, Pennsylvania, United States

Thonburi Trang Hastanesi; 🇹🇭 Thailand, Thailand

Istanbul University Cerrahpasa; 🇹🇷 Istanbul, Turkey

Acıbadem International Joint Center; 🇹🇷 Istanbul, Turkey

Acibadem LABMED Laboratories; 🇹🇷 Istanbul, Turkey

Acıbadem Mehmet Ali Aydınlar University; 🇹🇷 Istanbul, Turkey