Antibiotic Prophylaxis, Dysbiosis, Gut -microbiota, Microbiome Analysis, Probiotic
Conditions
Keywords
Gut Microbiome, Intestinal Dysbiosis, Surgical Site Infection, Probiotics, Antibiotic Prophylaxis, Human Milk Oligosaccharides (HMO), Shotgun Metagenomic Sequencing, Short-Chain Fatty Acids (SCFAs)
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.
Interventions
DRUGPlacebo Capsule
Participants will receive an inert placebo capsule that matches the probiotic capsule in size, shape, and color. The placebo will be administered orally twice daily, starting 2 weeks before surgery and continuing for 2 weeks postoperatively.
DIETARY_SUPPLEMENTProbiotic with Human Milk Oligosaccharides (HMO)
Participants will receive a dual-strain probiotic containing Human Milk Oligosaccharides (HMO) in capsule form. The probiotic will be administered orally twice daily, starting 2 weeks before surgery and continuing for 2 weeks postoperatively.
Sponsors
Acibadem University
Acibadem Maslak Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
In addition to participants, care providers, investigators, and outcomes assessors, the study's pharmacy personnel responsible for dispensing the intervention are also masked to the group assignments. Placebo and probiotic capsules are prepared to be identical in appearance and packaging, ensuring that no party involved in the trial can distinguish between the two interventions. Randomization and allocation are managed by an independent third party to maintain blinding integrity throughout the study.
Intervention model description
This study uses a parallel group design where participants are randomly assigned to one of two independent arms. One group receives routine antibiotic prophylaxis with a placebo capsule, while the other group receives routine antibiotic prophylaxis combined with a dual-strain probiotic containing Human Milk Oligosaccharides (HMO). The interventions are administered concurrently over the perioperative period to evaluate their effects on gut microbiome balance and patient recovery. Randomization and blinding ensure unbiased comparisons between the groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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 |
| 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 |
Countries
Thailand, Turkey (Türkiye), United States
Contacts
Primary Contactİbrahim Tuncay, Prof. Dr.
Backup ContactGöksel Dikmen, Assoc. Prof. Dr
Outcome results
None listed