Washed Microbiota Transplantation for Malnutrition After Nonphysiological Reconstruction of the Upper Gastrointestinal Tract

An Open-label, Multicenter, Randomized Clinical Trial for Malnutrition After Nonphysiological Reconstruction of the Upper Gastrointestinal Tract: Washed Microbiota Transplantation Via Mid-gut Tube Versus Colonic Transendoscopic Enteral Tube

This is a prospective, randomized, multicenter study to evaluate WMT in improving nutritional status in malnourished patients who underwent nonphysiological reconstruction of the upper gastrointestinal tract. In this multicenter trial, sixty-two patients will be enrolled in forteen Chinese sites. Participants will be randomized at a ratio of 1:1 to receive three WMTs through either mid-gut tube or colonic TET. After WMT, each participant will receive free diet plus home enteral nutrition. Home enteral nutrition should last for 2 months at home, with blood, urine and stool samples taken and stored at baseline and 2 months after WMT.

Background: Malnutrition is a common complication of nonphysiological reconstruction of the upper gastrointestinal tract. The potential of washed microbiota transplantation (WMT) in improving nutritional status have been reported. The surgery procedure alters the anatomy and physiology of the digestive tract, which might impact the efficacy and safety of WMT when choosing different delivery way. This study aims to explore the optimal delivery of WMT in malnourished patients after rerouting of the upper gastrointestinal tract.

Methods and design: This multicenter, open-label, and randomized controlled trial will be conducted at forteen hospitals in China. Enteral nutrition (EN) will be administrated at enrollment. Participants will be then randomized at a ratio of 1:1 to receive three WMTs through either mid-gut tube or colonic transendoscopic enteral tubing (TET). Then the patients will receive free diet coupled with home enteral nutrition (HEN) for 8 weeks in both groups, with blood, urine and stool samples taken and stored at baseline and 2 months after WMT. The observation duration is 8 weeks. The primary endpoint is nutritional status of the patients. The nutritional status data obtained at baseline and 8 weeks after discharge includes body mass index (BMI) and skeletal muscle index (SMI). The secondary endpoints are nutritional assessment, nutrition-based laboratory indices, 60-day readmission rate, quality of life, gastrointestinal symptom scale, the safety of WMT and further analysis of the biological specimens.

Conclusion: It is estimated that WMT would help improve nutrition status. Moreover, this trial has the potential to identify the optimal delivery of WMT for patients undergoing nonphysiological reconstruction of the upper gastrointestinal tract.

Inclusion Criteria:

• Patients undergone nonphysiological reconstruction of the gastrointestinal tract (such as Billroth-II, Roux-en-Y, Child, Whipple reconstruction)
• Aged over 18 years old;
• Malnutrition is assessed by Nutritional Risk Screening 2002 score≥3 and Patient Generated Subjective Global Assessment (PG-SGA) score≥4;
• Written informed consent;

Exclusion Criteria:

• Expected survival time < 3 months;
• Still on anti-tumor therapy or it is expected during the visit;
• Complicated with ascites or edema caused by malnutrition;
• Known organic gastrointestinal disease (e.g., gastrointestinal infection, inflammatory bowel disease, or radiation enteritis);
• Undergone other gastrointestinal surgery (e.g., enterectomy, enterostomy, or gastrostomy) except appendectomy or anal fistula surgery;
• Complicated with contraindications of enteral nutrition such as ileus, active gastrointestinal bleeding, and shock;
• Cannot tolerate gastroscopy or colonoscopy;
• Severe comorbidities (e.g., diabetes, cardiopulmonary failure, severe liver or or kidney diseases);
• Complicated with other wasting diseases (e.g., active tuberculosis, hyperthyroidism, diabetes, HIV, active hepatitis, hip fracture, craniocerebral injury, etc.);
• A history of anti-infective treatment within 30 days before enrollment; or need anti-infective treatment at the time of enrollment; or unwilling to stop taking drugs that affect gut microbes, such as probiotics;
• Can not tolerate oral enteral nutrition;
• Women who are pregnant or breastfeeding;
• Participating in another clinical trial;
• Deemed unsuitable for inclusion by the investigators.