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

Official title

Impact of Probiotics Combined with Antibiotic Prophylaxis on Gut Microbiome Balance in Patients Undergoing Elective Orthopedic Surgery, Double-Blinded Randomized Controlled Trial

Overview

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

• Drug Placebo 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 supplement Probiotic 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.

Primary outcome measures

• Maintenance of Gut Microbiome Balance [Time frame: 2 weeks preoperatively (T0) to 1 month postoperatively (T4).]

Secondary outcome measures (6)

• Firmicutes/Bacteroidetes Ratio [Time frame: 2 weeks preoperatively (T0) to 1 month postoperatively (T4).]
• Short-Chain Fatty Acid (SCFA) Production [Time frame: 2 weeks preoperatively (T0) to 1 month postoperatively (T4).]
• Dysbiosis Index [Time frame: 2 weeks preoperatively (T0) to 1 month postoperatively (T4).]
• Microbiome health index ( MHI) OR Microbiome health index for post-antiobiotic (MHI- A) [Time frame: 2 weeks preoperatively (T0) to 1 month postoperatively (T4).]
• WHO-5 Well-being Index [Time frame: 1 week preoperatively (T1) and 2 weeks postoperatively (T3).]
• EuroQol 5-Dimension (EQ-5D) score. [Time frame: 1 week preoperatively (T1) and 2 weeks postoperatively (T3).]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Turkey (Türkiye) · 4 centers

• Istanbul University Cerrahpasa — Istanbul
• Acıbadem International Joint Center — Istanbul
• Acibadem LABMED Laboratories — Istanbul
• Acıbadem Mehmet Ali Aydınlar University — Istanbul

United States · 1 center

• Parvizi Surgical Innovation — Philadelphia

Thailand · 1 center

• Thonburi Trang Hastanesi — Thailand

Publications

• Anthony WE, Wang B, Sukhum KV, D'Souza AW, Hink T, Cass C, Seiler S, Reske KA, Coon C, Dubberke ER, Burnham CD, Dantas G, Kwon JH. Acute and persistent effects of commonly used antibiotics on the gut microbiome and resistome in healthy adults. Cell Rep. 2022 Apr 12;39(2):110649. doi: 10.1016/j.celrep.2022.110649. PMID 35417701
• Rios JL, Bomhof MR, Reimer RA, Hart DA, Collins KH, Herzog W. Protective effect of prebiotic and exercise intervention on knee health in a rat model of diet-induced obesity. Sci Rep. 2019 Mar 7;9(1):3893. doi: 10.1038/s41598-019-40601-x. PMID 30846801
• Akagawa Y, Kimata T, Akagawa S, Yamaguchi T, Kato S, Yamanouchi S, Hashiyada M, Akane A, Kino M, Tsuji S, Kaneko K. Impact of Long-Term Low Dose Antibiotic Prophylaxis on Gut Microbiota in Children. J Urol. 2020 Dec;204(6):1320-1325. doi: 10.1097/JU.0000000000001227. Epub 2020 Jul 2. PMID 32614253
• Huang Z, Chen J, Li B, Zeng B, Chou CH, Zheng X, Xie J, Li H, Hao Y, Chen G, Pei F, Shen B, Kraus VB, Wei H, Zhou X, Cheng L. Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice. Ann Rheum Dis. 2020 May;79(5):646-656. doi: 10.1136/annrheumdis-2019-216471. Epub 2020 Mar 23. PMID 32205337
• Coulson S, Butt H, Vecchio P, Gramotnev H, Vitetta L. Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles. Inflammopharmacology. 2013 Feb;21(1):79-90. doi: 10.1007/s10787-012-0146-4. Epub 2012 Jul 22. PMID 22821424
• Kullar R, Chisari E, Snyder J, Cooper C, Parvizi J, Sniffen J. Next-Generation Sequencing Supports Targeted Antibiotic Treatment for Culture Negative Orthopedic Infections. Clin Infect Dis. 2023 Jan 13;76(2):359-364. doi: 10.1093/cid/ciac733. PMID 36074890
• Ramires LC, Santos GS, Ramires RP, da Fonseca LF, Jeyaraman M, Muthu S, Lana AV, Azzini G, Smith CS, Lana JF. The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut? Int J Mol Sci. 2022 Jan 27;23(3):1494. doi: 10.3390/ijms23031494. PMID 35163417
• Chisari E, Wouthuyzen-Bakker M, Friedrich AW, Parvizi J. The relation between the gut microbiome and osteoarthritis: A systematic review of literature. PLoS One. 2021 Dec 16;16(12):e0261353. doi: 10.1371/journal.pone.0261353. eCollection 2021. PMID 34914764

Identifiers

NCT: NCT06791993 · 2024-KAEK-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗