IDDF2023-ABS-0107 Nanocoating mediated whole gut microbiota transplantation for enhanced biotherapy of inflammatory bowel disease

Background

Fecal microbiota transplantation (FMT) uses fecal microbiota to treat diseases but shows a limited therapeutic effect on small intestinal diseases due to the unique biogeography of small intestinal microbiota.

Methods

Small intestinal fluid and feces from Sprague-Dawley mice were homogenized and filtrated by a 70 μm pore nylon filter to obtain a microbiota solution. Chitosan and alginate were successively coated on the surface of microbe based on the electrostatic interaction. The nanocoating of microbe was characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), size distribution, zeta potential, etc. Resistance assessment of nanocoated microbiota was investigated in simulated gastric fluid in vitro. Fluorescently-labeled Escherichia coli was used for evaluating the impact of nanocoating on bacterial intestinal colonization. Germ-free mouse experiment was implemented for analyzing gut microbiota distribution after FMT, whole gut microbiota transplantation (WMT), FMT by nanocoating (NanoFMT) and WMT by nanocoating (NanoWMT). The efficacy of different groups was investigated by two mouse models, including the Salmonella typhimurium induced colitis model and 5-fluorouracil-induced mucositis. Stool, blood and intestinal tissue samples were collected from all mice. Gut microbiota, cytokine levels and histopathology were subsequently analyzed.

Results

The alternate transformation of zeta potential demonstrated the attachment of chitosan and alginate on the surface of microbe. The changed morphology of microbe was presented by size distribution, TEM and AFM after nanocoating. Nanocoating did not impact the growth performance of microbiota but significantly ameliorated gastrointestinal tolerance in vitro and in vivo models. Significantly, the bacterial count increased 67.8 folds on the small intestine after nanocoating, visually observed by in vivo imaging system based on the fluorescence label of bacteria. Gut biogeography of microbiota was more reasonable in the WMT group than FMT group for the germ-free model. NanoWMT showed the best performance on reversing intestinal contraction, villus disorders and inflammatory levels for the treatment of mouse mucositis, especially on gut microbiota balance.

Conclusions

WMT better adjusted the microbiota distribution of the whole gut, while the nanocoating technology further enhanced the therapeutic effect of WMT for small intestinal diseases.