Changes in Oral and Gut Microbiome Diversity in Patients undergoing Total Joint Arthroplasty and Receiving Perioperative Antibiotics, a Pilot Case Series

Background Perioperative antibiotic prophylaxis is common practice in joint replacement surgery.8 Antibiotics can cause dysbiosis to the native microbiome which can negatively affect patient health and may play a role Periprosthetic Joint Infection (PJI). The purpose of this pilot feasibility study was to evaluate if (1) we can measure a change in the microbiome of patients undergoing primary hip and knee replacements who receive routine peri-operative antibiotics and (2) at what time point does a patient’s microbiome return to pre-surgery profiles? Methods The study was approved by the University Institutional Review Board (IRB). Consented participants were provided stool and saliva collection kits for: Time (T) 1-1 week prior; T2: 1-week after; T3: 3-months after; and T4: 6-months after Total Joint Arthroplasty (TJA). All samples were reliably shipped and then stored at -80° C. Clinical characteristics and outcomes were obtained for 2 years post-operatively. Bacterial Deoxyribonucleic Acid (DNA) from the stool and saliva samples was analyzed via 16S rDNA gene sequence amplification. DNA extraction was carried out using the Q1 Aamp DNA stool mini kit. DNA concentration and quality was determined by Fragment Analysis on NanoAmp 100 spectrophotometer. Calculated α-diversity and β-diversity measures were summarized using univariate statistics. For α-diversity, a paired t-test was used to assess change between time points (T1 to T2, T1 to T3 and T1 to T4). The effect size of change was calculated and interpreted using Cohen’s d.21 For β-diversity, detrended correspondence analysis (DCA) ordination plots were generated for saliva and stool separately. Results Eight patients agreed to participate. Table 1 provides patient demographics, clinical characteristics, and post-operative antibiotic regime. The patient population was 71.4% female, mean age 72.6+9.2 years, mean Body Mass Index (BMI) 25.6+4.4. All participants were followed up for 2 years and did not have a PJI or disrupted gut microbiota-related complications. We found a small reduction in absolute α-diversity within a week of TJA and antibiotic use, but the effect (Cohen’s d) was more prominent in the oral microbiome than the gut [0.46 (-0.34, 1.22) vs. 0.16 (-0.59, 0.90), respectively], Although there was a greater microbiota diversity in the gut than in the oral cavity, only insignificant changes in α- or β-diversity in the gut after undergoing antibiotic prophylaxis were observed during the postoperative period. Conclusion Out pilot study showed that antibiotic prophylaxis did not significantly impact gut microbiota, and that patient’s microbiome appears to return to normal at 3 months after TJA. We conclude that comparing absolute α-diversity in stool over time is more feasible than measuring changes in Proteobacteria or β-diversity when performing large prospective studies.