Metagenomic sequencing revealed significant differential abundance species between FMT.R and FMT.NR
nausea, flatulence, diarrhea, abdominal pain, PD, depression, gastrointestinal disorders
ADVERSE EVENTS, GASTROINTESTINAL DISORDERS
As our data showed, FMT had a positive effect on clinical outcomes in patients with PD, and remarkable improvement was observed in gastrointestinal disorders. Most patients experienced better bowel movement and had less abdominal pain, flatulence, or other symptoms, and the quality of life was significantly improved in most participants. After 3 consecutive weeks of FMT or placebo intervention, the alpha and beta diversity in gut microbiota did not change significantly (Supplementary Figure S2).It is noteworthy that we found that some patients showed obvious improvement in PD symptoms after treatment, while others did not. According to the change in the MDS-UPDRS Part 2 score, which is the Motor Experiences of Daily Living (M-EDL) score, patients were nominated as FMT responders (Comparison of gut microbiota between responders and non-responders after FMT treatment. A: patients who underwent FMT treatment had different responses during follow-up according to the MDS-UPDRS score, and the FMT cohort was subdivided into FMT responders (FMT.R, red lines) and FMT non-responders (FMT.NR, cyan lines) based on MDS-UPDRS 2, FMT.R showed a remarkable decrease in MDS-UPDRS total, part 2, part 3, and part 4 score (*: P < .05, **: P < .01, ***: P < .001, ***: P < .0001, generalized estimating equation); B: schematic illustration of subgroup analysis in the FMT arm; C: α-diversity of gut microbiota in FMT.NR and FMT.R subgroups according to estimate of richness; D: Principal coordinates analysis (PCoA) of the microbiota based on the unweighted unifrac distance between FMT.R and FMT.NR subgroups at the end of this trial by R package Vegan; E: metagenomic sequencing analysis showed there are 20 microbial species with significantly different abundance by comparing FMT.NR with FMT.R subgroup; F: the correlation analysis of gut microbiota taxa and clinic outcome of gastrointestinal disorders, PD symptoms, cognition, and depression (*Totally, 3 adverse events occurred in the FMT arm, 1 nausea and 1 flatulence in the responders, and 1 diarrhea in the non-responders (Supplementary table S3). The GEE model was also applied to evaluate the differences between the two subgroups (Supplementary Table S4). As for MDS-UPDRS score, FMT.R had a significant larger decrease in the total score, part 2 score, part 3 and part 4 score at the end of the follow-up, while FMT.NR did not showed any significant change regarding these indicators. Meanwhile, the MDS-UPDRS part 1 score changed remarkably in the FMT.R subgroup, with no additional change between FMT.R and FMT.NR subgroups. These results suggest that subgroups had different responses to PD improvement. Meanwhile, by assessment of IBS-SSS, GSRS, IBS-QOL, and
Bristol stool scale, FMT.NR showed significant improvement in bowel movement, but only GSRS score had an additional decrease in FMT.R compared to FMT.NR. The evaluation for cognitive function by MMSE and MOCA scale also showed a significant improvement in the FMT.NR with no additional change in FMT.R, suggesting that patients had a noticeable change in the gastrointestinal disorders as well as cognitive function, regardless of their responses in PD symptoms.Given that the different responses to FMT treatment might result from individual variations in gut microbiota (