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前瞻性研究揭示了 2 型糖尿病患者接受粪便微生物群移植治疗的临床应答的宿主微生物决定因素。

Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients.

机构信息

Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Front Cell Infect Microbiol. 2022 Mar 25;12:820367. doi: 10.3389/fcimb.2022.820367. eCollection 2022.

DOI:10.3389/fcimb.2022.820367
PMID:35402293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8990819/
Abstract

BACKGROUND

Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.

METHODS

We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.

RESULTS

We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p<0.01), blood glucose (from 8.483 ± 0.497 to 7.286 ± 0.454 mmol/L, p<0.01), and uric acid (from 309.4 ± 21.5 to 259.1 ± 15.8 µmol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 ± 0.600 to 5.471 ± 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family and the genus (family ) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83.

CONCLUSION

Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of and in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.

摘要

背景

越来越多的证据表明,肠道微生物组(GM)的改变有助于 2 型糖尿病(T2DM)的发展,粪便微生物群移植(FMT)成功治疗了各种人类疾病。然而,FMT 治疗对 T2DM 患者的益处尚不清楚。

方法

我们招募了 17 名 T2DM 患者进行非盲、单臂干预试验的 FMT。共招募了 20 名健康个体作为基线对照。在接受来自健康供体的 FMT 治疗 12 周后,评估 17 名 T2DM 患者的 HbA1c%和代谢参数变化。在 FMT 治疗前和治疗后 12 周,通过粪便样本的 16S rRNA 基因扩增子测序来描述 GM 组成。

结果

我们发现 FMT 可以重建 T2DM 患者的 GM。我们观察到 HbA1c%(从 7.565±0.148 降至 7.190±0.210,p<0.01)、血糖(从 8.483±0.497 降至 7.286±0.454mmol/L,p<0.01)和尿酸(从 309.4±21.5 降至 259.1±15.8μmol/L,p<0.01)显著降低,而餐后 C 肽(从 4.503±0.600 升至 5.471±0.728ng/ml,p<0.01)显著增加。在 FMT 治疗后 12 周时,对这些检测结果进行了仔细评估,我们发现个体对 FMT 治疗的反应存在差异。在 17 名 T2DM 患者中,有 11 名患者的 T2DM 症状明显改善。与非应答者相比,FMT 应答者预处理粪便中的 科和 属(科)水平显著升高,这可以通过曲线下面积为 0.83 来预测临床反应。

结论

我们的研究结果表明,某些 T2DM 患者可能从 FMT 中受益,患者粪便中预处理的 科和 属丰度可能作为选择接受 FMT 的 T2DM 患者的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/e41f51a932c3/fcimb-12-820367-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/5e989fcef452/fcimb-12-820367-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/7f56add00212/fcimb-12-820367-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/ae372ec7f771/fcimb-12-820367-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/e41f51a932c3/fcimb-12-820367-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/5e989fcef452/fcimb-12-820367-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/7f56add00212/fcimb-12-820367-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/ae372ec7f771/fcimb-12-820367-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/8990819/e41f51a932c3/fcimb-12-820367-g004.jpg

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