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

NCT06791993 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2024-KAEK-03
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 6

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.

Conditions

Dysbiosis; Gut -microbiota; Microbiome Analysis; Probiotic; Antibiotic Prophylaxis

Keywords

Gut Microbiome; Intestinal Dysbiosis; Surgical Site Infection; Probiotics; Antibiotic Prophylaxis; Human Milk Oligosaccharides (HMO); Shotgun Metagenomic Sequencing; Short-Chain Fatty Acids (SCFAs)

Outcome Measures

Primary Outcomes (1)

• Maintenance of Gut Microbiome Balance

  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.

  2 weeks preoperatively (T0) to 1 month postoperatively (T4).

Secondary Outcomes (6)

• Firmicutes/Bacteroidetes Ratio

  2 weeks preoperatively (T0) to 1 month postoperatively (T4).

• Short-Chain Fatty Acid (SCFA) Production

  2 weeks preoperatively (T0) to 1 month postoperatively (T4).

• Dysbiosis Index

  2 weeks preoperatively (T0) to 1 month postoperatively (T4).

• Microbiome health index ( MHI) OR Microbiome health index for post-antiobiotic (MHI- A)

  2 weeks preoperatively (T0) to 1 month postoperatively (T4).

• WHO-5 Well-being Index

  1 week preoperatively (T1) and 2 weeks postoperatively (T3).

Study Arms (2)

Routine Antibiotic Prophylaxis + Placebo

PLACEBO COMPARATOR

This arm receives routine antibiotic prophylaxis with a single dose of intravenous Cefazolin and a placebo capsule to match the probiotic intervention.

Drug: Placebo Capsule

Routine Antibiotic Prophylaxis + Probiotics

EXPERIMENTAL

This arm receives routine antibiotic prophylaxis with a single dose of intravenous Cefazolin and a dual-strain probiotic containing Human Milk Oligosaccharides (HMO).

Dietary Supplement: Probiotic with Human Milk Oligosaccharides (HMO)

Interventions

Placebo Capsule DRUG

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.

Routine Antibiotic Prophylaxis + Placebo

Probiotic with Human Milk Oligosaccharides (HMO) DIETARY_SUPPLEMENT

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.

Also known as: Dual-Strain Probiotic

Routine Antibiotic Prophylaxis + Probiotics

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Acibadem Maslak Hospital: lead
• Acibadem University: collaborator

Study Sites (6)

Parvizi Surgical Innovation

Philadelphia, Pennsylvania, 19107, United States

Location

Thonburi Trang Hastanesi

Thailand, 40002, Thailand

Location

Istanbul University Cerrahpasa

Istanbul, 34098, Turkey (Türkiye)

Location

Acıbadem International Joint Center

Istanbul, 34457, Turkey (Türkiye)

Location

Acibadem LABMED Laboratories

Istanbul, 34752, Turkey (Türkiye)

Location

Acıbadem Mehmet Ali Aydınlar University

Istanbul, 34752, Turkey (Türkiye)

Location

Related Publications (10)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Favazzo LJ, Hendesi H, Villani DA, Soniwala S, Dar QA, Schott EM, Gill SR, Zuscik MJ. The gut microbiome-joint connection: implications in osteoarthritis. Curr Opin Rheumatol. 2020 Jan;32(1):92-101. doi: 10.1097/BOR.0000000000000681.

  PMID: 31724973 BACKGROUND

• Boer CG, Radjabzadeh D, Medina-Gomez C, Garmaeva S, Schiphof D, Arp P, Koet T, Kurilshikov A, Fu J, Ikram MA, Bierma-Zeinstra S, Uitterlinden AG, Kraaij R, Zhernakova A, van Meurs JBJ. Intestinal microbiome composition and its relation to joint pain and inflammation. Nat Commun. 2019 Oct 25;10(1):4881. doi: 10.1038/s41467-019-12873-4.

  PMID: 31653850 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Dysbiosis; Surgical Wound Infection

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wound Infection; Infections; Postoperative Complications

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Javad Parvizi, Prof. Dr.

  International Joint Center Acibadem, Parvizi Surgical Innovation

  STUDY CHAIR

• Emanuele Chisari, Dr., Ph.D.

  Parvizi Surgical Innovation, University of Groningen

  STUDY DIRECTOR

Central Study Contacts

İbrahim Tuncay, Prof. Dr.

CONTACT

+90 212 304 43 78; ituncay@gmail.com

Göksel Dikmen, Assoc. Prof. Dr

CONTACT

+90 505 202 1748; goksel.dikmen@acibadem.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: January 24, 2025
• Study Start: February 1, 2025
• Primary Completion: August 1, 2025
• Study Completion: October 1, 2025
• Last Updated: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Data access will be granted to researchers who provide a methodologically sound proposal. Proposals should be directed to goksel.dikmen@acibadem.com To gain access, data requestors will need to sign a data access agreement.

Locations

TU (4); US (1); TH (1)