Ultrafine Bubble Water Usefulness in Fecal Microbiota Transplantation: Recognition of Transplanted Microbiota in Intestinal Epithelial Cells

Background: Indications for various diseases such as diabetes mellitus and metabolic syndrome, etc. of Fecal Microbiota Transplantation (FMT) have been investigated. For the establishment of the FMT therapy, the examination of the solvent has not been carried out, though the use of the physiological saline is fixed, at present. We have produced the Mr. Shimizu made ultrafine bubble water (UFB) that produces a larger number of bubbles than existing UFB.Objective: To verify the usefulness of UFB, we prepared a conventional Saline and UFB-prepared microbial preparation (Bio3); (Bio3/Saline) and (Bio3/UFB). The bacterial preparations, Bio3, contain glycated bacteria, lactic acid bacteria, and butyric acid bacteria. FMT was carried out to the diabetic model mouse using these microbial preparations, and whether the disease state was improved was examined. Cultured intestinal epithelial cells (CaCO-2) were also used to test for differentiation by UFB and Saline from variations in several receptors that recognize microbiota-mRNA. In addition, glucose uptake into cells was measured.Methods: FMT with (Bio3/UFB) and (Bio3/Saline) was performed in streptozotocin-induced diabetic mice (STZ-mice) in duplicate at 0, 7 days. Blood glucose levels (7, 14 days) and blood insulin levels (14 days) were measured. Cultured intestinal epithelial cells were also used to test for differentiation by UFB and Saline from change in several receptors that recognize microbiota-mRNA (Toll-like receptors, NOD-like receptors, and RIG-I-like receptors). In addition, glucose uptake into cells was measured using fluorescently labeled glucose analog (NBDG).Results: UFB could reduce the blood glucose level of STZ-induced diabetic model mice. However, no such effects were observed in Saline. Stimulation of serially diluted Bio3 with UFB-suspension were showed significant alteration in TLR4 and IL-1B-uPNA. The amount of glucose uptake in the (Bio3/UFB) group was significantly different at 30 min, inhibited or delayed. Conclusion: It is concluded that UFB-mediated cross-talk between intestinal bacteria and intestinal epithelial cells and inhibition or delay of intestinal epithelial glucose uptake may have been associated with the reduction of blood glucose levels in diabetic model mice. The superiority of UFB as a suspension used for the transfer of bacteria has been suggested.