IDDF2023-ABS-0057 Nanocapsule of gut microbiota for enhancing efficacy of fecal microbiota transplantation

Background

The invasive nasointestinal and recal administration was commonly used for fecal microbiota transplantation (FMT). Microbiota powder capsule could be non-invasively administrated, but its preparation caused the dead of anaerobic bacteria by the long-time freeze drying. Therefore, a novel strategy combining non-invasive administration with high microbiota activity is needed.

Methods

Silk fibroin and phosphatidylcholine were used for constructing nanocapsule of gut microbiota by layer-by-layer strategy. The coating efficiency of the nanocapsule was represented by a confocal image and flow cytometry analysis. The morphology of the nanocapsule was analyzed by transmission electron microscopy and size distribution. Resistance assessment of gut microbiota nanocapsule was investigated in simulated gastric fluid and mice, respectively. The efficacy of FMT using nanocapsule (NanoFMT) was compared with common FMT in the treatment of colitis model. Stool, blood and intestinal tissue samples were collected from all mice. Gut microbiota, cytokine levels and histopathology were analyzed to evaluate the therapeutic effect of NanoFMT.

Results

Confocal images demonstrated the existence of silk fibroin and phosphatidylcholine labeled by fluorescein on the surface of microbiota. Flow cytometry showed a high coating ratio was present at 74.4%, indicating that nanocapsule of gut microbiota could be acquired (IDDF2023-ABS-0057 Figure 1A). Nanocapsule did not impact the growth performance of gut microbiota but significantly ameliorated gastrointestinal tolerance in vitro and in vivo models. Comparing with common FMT, NanoFMT by gut microbiota nanocapsule remarkably decreased the dead ratio of mice, reversed intestinal contraction and delayed inflammatory disorder during the treatment of the colitis model induced by Salmonella typhimurium (IDDF2023-ABS-0057 Figure 1B). Moreover, NanoFMT group represented better alpha diversity and beta diversity of gut microbiota than FMT group and completely suppressed Salmonella typhimurium (IDDF2023-ABS-0057 Figure 1C). Oral administration of nanocapsule is more acceptable to patients than invasive delivery (nasointestinal and recal administration). Besides, a nanocapsule could be prepared within 1 hour, which was remarkably shorter than the preparation of a common capsule (2-3 days), hence easily preserving the activity of anaerobes.

Conclusions

NanoFMT by gut microbiota nanocapsule rendered better therapeutic effect and gut microbiota regulation than common FMT for treating inflammatory bowel disease, showing excellent potential in clinical application.