Nanjing Consensus on Methodology of Washed Microbiota Transplantation

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Nanjing Consensus on Methodology of Washed Microbiota Transplantation

Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for various gastrointestinal and systemic disorders. However, the methods and outcomes of FMT vary significantly across different centers worldwide. To address this issue and improve the clinical practice and trials related to FMT, the Fecal Microbiota Transplantation-Standardization Study Group developed the Nanjing Consensus on Washed Microbiota Transplantation (WMT). This consensus provides detailed guidance on the methodology of WMT, which differs from the manually processed FMT described in previous expert recommendations.

Development of the Consensus

The Nanjing Consensus was developed by a panel of 28 experts from 22 hospitals or institutes across 15 cities. These experts were divided into five groups based on their expertise: Group 1 focused on donor screening, Group 2 on the washing microbiota protocol, storage, and transport, Group 3 on patient preparation, Group 4 on delivery decision, and Group 5 on safety and management. The consensus process involved a Delphi method and a face-to-face plenary meeting. The best available evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.

After three rounds of anonymous voting and editing, consensus was reached for all 31 statements. All statements passed the 80% agreement threshold in each round. The final consensus was presented to all 28 panel members on December 12, 2019, in Nanjing, China.

Donor Screening

The first part of the consensus focuses on donor screening, which is crucial for ensuring the safety and efficacy of WMT. The following statements were agreed upon:

  1. Education for Candidate Donors: Education targeting candidate donors should be conducted to increase their willingness to donate feces.
  2. Informed Consent: Candidates must be informed of the potential risks and benefits of FMT for recipients.
  3. Questionnaire Interview: A questionnaire should be conducted to exclude candidates with risk factors in their medical history and lifestyle habits.
  4. Face-to-Face Interview: Donors who pass the primary screening must undergo a face-to-face interview with a trained physician.
  5. Laboratory Screening: Potential donors must undergo blood and stool testing to rule out transmissible infectious diseases and potential dysbiosis-related diseases within three weeks before donation.
  6. Monitoring Screening: Donors with repeat donations should undergo monitoring screening after holidays, travel, or recovery from sickness.
  7. Questionnaire on Donation Day: Eligible donors must complete a questionnaire on the day of donation to exclude any interim risk factors.
  8. Reporting Changes: Donors should report any blood, mucus, or changes in stool consistency noticed in the donated stool.

Washing Microbiota Protocol, Storage, and Transport

The second part of the consensus addresses the preparation, storage, and transport of washed microbiota:

  1. Reduced Adverse Events: Washed microbiota preparation contributes to reduced FMT-related adverse events (AEs).
  2. Quality Control: Quality control of washed microbiota preparation is pivotal for improving the acceptance of FMT from patients and physicians.
  3. Time Limitation: Limiting the time from stool collection to microbiota delivery is conducive to preserving functional fecal microbiota.
  4. Qualified Facilities: Quality control of washed microbiota preparation is dependent on appropriately qualified facilities.
  5. Storage at -80°C: Washed microbiota can be stored at -80°C for up to one year by adding glycerol to a final concentration of 10%. Frozen microbiota should be thawed in a warm (37°C) water bath before use.
  6. Transportation: Frozen washed microbiota materials should be sealed and remain frozen during transportation.
  7. Temporary Storage: Frozen washed microbiota suspensions can be stored with dry ice or in a freezer at <-20°C for temporary storage or transportation.

Patient Preparation

The third part of the consensus focuses on preparing patients for WMT:

  1. Informed Consent: Patients or their guardians should be informed of the donor source and the methods of microbiota preparation.
  2. Antibiotics: Antibiotics should be stopped 12-48 hours before microbiota delivery.
  3. Bowel Lavage: The decision on bowel lavage before microbiota delivery should be based on patients’ conditions.
  4. Blood Testing: All recipients of WMT should undergo blood testing for transmissible infections.

Delivery Decision

The fourth part of the consensus addresses the methods of delivering washed microbiota:

  1. Aspiration Pneumonia: Aspiration pneumonia is a serious AE that can be related to FMT delivery methods.
  2. Mid-Gut Delivery: Washed microbiota can be delivered into the mid-gut through the endoscopic channel, nasojejunal tube, gastrostomy tube, or jejunostomy tube.
  3. Colonic TET: Washed microbiota suspensions can be delivered through colonic trans-endoscopic tubing (TET).
  4. Colonoscopy: Colonic infusion under colonoscopy can be considered when a single infusion is sufficient for the patient.
  5. Enema: Microbiota delivered by enema might be less effective than colonoscopy and colonic TET.
  6. Capsules: Conscious patients with Clostridium difficile infection (CDI) who can tolerate capsules are suitable to choose capsulized preparation of washed microbiota.
  7. Nasogastric Tube: Suitable conscious pediatric patients who have no other alternative can be given washed fecal microbiota suspensions through the nasogastric tube.

Safety and Management

The fifth part of the consensus focuses on the safety and management of WMT:

  1. Clinical Governance: The clinical governance of WMT is mandatory, and the service should be provided by trained physicians.
  2. Stool Sample Storage: The stool sample from a donor should be stored for at least two years for safety traceability. The donor screening documentation and laboratory records should be stored for at least ten years.
  3. Regional WMT Center: Regional WMT centers in hospitals are encouraged to provide professional WMT services and microbiota-related research.
  4. Laboratory Conditions: The laboratory conditions for WMT are required to meet level 2 and are encouraged to meet level 3.
  5. Staff Training: The staff of the WMT center must receive training on WMT.

General Steps for the Preparation of Washed Microbiota Suspensions

The consensus also provides general steps for the preparation of washed microbiota suspensions:

  1. Feces Collection: Feces should preferably be collected on-site in a disposable feces container in a dedicated room only for donors.
  2. Disposable Devices: All devices directly contacting fecal matters used for fecal collection, suspension filtration, centrifugation, and washing should be disposable.
  3. Fecal Quantity: Feces from adults less than 50 g are not recommended for processing using an automatic purification system for enriching microbiota.
  4. Centrifugation: The fecal suspension is transferred to centrifugation tubes for centrifugation at 700 g for three minutes, and the supernatant is discarded.
  5. Repeated Washing: This process is repeated three times using sterile saline to make the suspension.
  6. Final Preparation: 10 cm³ (about 1.0 x 10¹³ bacteria) of final precipitated microbiota is the basic unit dose for clinical use. The volume ratio of final precipitation to vector solution is 1:2 for making suspensions for fresh or frozen use.
  7. Anaerobic Processing: Anaerobic fecal processing is encouraged if possible.

Conclusion

The Nanjing Consensus on Methodology of Washed Microbiota Transplantation provides comprehensive guidance on the standardization of WMT. By addressing key aspects such as donor screening, microbiota preparation, patient preparation, delivery methods, and safety management, this consensus aims to improve the clinical practice and outcomes of FMT. The detailed recommendations and steps outlined in the consensus are expected to enhance the acceptance and efficacy of WMT in clinical settings.

doi.org/10.1097/CM9.0000000000000954

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