[Effect of fecal microbiota transplantation on type 1 diabetes mellitus in non-obese diabetic mice and its underlying mechanism].

To investigate the effects of fecal microbiota transplantation (FMT) on non-obese diabetic (NOD) mice of type 1 diabetes mellitus (T1DM) and its underlying mechanisms. A total of 8-9 week-female NOD mice were randomly divided into control (=36) and FMT groups (=36) according to the random number table. Fecal microbiota from C57BL/6 mice were transplanted into FMT group, and control group were transplanted with microbiota from themselves, once every two days for 5 times. The insulitis score and incidence of T1DM were compared between two groups;16S rRNA gene sequencing was used to evaluate the structure of fecal bacteria in NOD mice. The expressions of intestinal barrier related genes were detected by real-time quantitative PCR. The proportions of regulatory T cells (Tregs), helper T cell (Th)-1 and Th17 in the enteric-pancreatic immune axis were detected by flow cytometry. Amino acid in serum was measured by amino acid metabolomics. Incidence of T1DM in NOD mice from FMT group was 40.9% (9/22), lower than 72.7% (13/22) from control group at 26 weeks of age (=0.034). FMT promoted colonization of probiotics such as , , and ; mRNA of intestinal barrier related genes were up-regulated in FMT group [ mucins(Muc)-1: 0.93±0.29 vs 2.97±0.79, =0.036; Muc2: 0.72±0.39 vs 10.70±3.54, =0.019;Muc3: 1.79±0.69 vs 10.97±2.78, =0.009;Muc4: 1.01±0.23 vs 2.42±0.49, =0.029;Occludin(Ocln): 0.96±0.08 vs 1.81±0.36, =0.045; Claudin(Cldn)-1:0.94±0.17 vs 2.20±0.43, =0.022] compared to control. The proportions of Treg in mesenteric lymphoid node, pancreatic lymph node and peyer's patches of FMT group [(6.10±0.49)% vs (7.54±0.27)%, =0.020;(5.28±0.39)% vs (6.42±0.34)%, =0.048;(6.78±0.42)% vs (7.88±0.13)%, =0.029] were increased compared to control,while proportions of Th1 [(1.02±0.06)% vs (0.83±0.06)%, =0.040;(0.82±0.10)% vs (0.56±0.05)%, =0.038;(1.28±0.12) vs (0.85±0.07), =0.012] and proportions of Th17 [(0.40±0.01)% vs (0.30±0.02)%, =0.004;(0.40±0.02)% vs (0.31±0.02)%, =0.008;(0.51±0.06) vs (0.36±0.02), =0.027] were decreased. The contents of leucine [(92.86±7.32) vs (91.87±12.62) μmol/L, =0.027], valine [(162.74±15.97) vs (155.89±25.70) μmol/L, =0.046] and isoleucine [(75.65±5.59) vs (73.61±9.67) μmol/L, =0.048] in serum were decreased in FMT group. FMT can alleviate insulitis and T1DM occurrence in NOD mice, of which mechanism may be related to remodeling gut microbiota and improving intestinal barrier function, affecting immune response of enteric-pancreatic immune axis, correcting amino acid metabolism disorder and reducing the accumulation of branch chain amino acids in NOD mice.