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粪便微生物移植对 CKD 小鼠菌群组成的影响。

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD.

机构信息

CarMeN Lab, INSA-Lyon, INSERM U1060, INRA, University Claude Bernard Lyon 1, 69100 Villeurbanne, France.

Department of Nephrology, Hospices Civils de Lyon, Lyon Sud Hospital, 69310 Pierre Bénite, France.

出版信息

Toxins (Basel). 2020 Nov 24;12(12):741. doi: 10.3390/toxins12120741.

Abstract

BACKGROUND

Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD.

METHODS

Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation.

RESULTS

Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function.

CONCLUSIONS

These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.

摘要

背景

慢性肾脏病(CKD)是一种以尿毒症毒素积累为特征的肾脏疾病,目前降低其浓度的策略有限。大量数据支持肠道微生物群在 CKD 并发症中的关键作用,以及作为尿毒症毒素产生的主要来源。在这里,我们探讨了粪便微生物群移植(FMT)是否可以减轻 CKD 小鼠的代谢并发症和尿毒症毒素积累。

方法

通过含有 0.25%(w/w)腺嘌呤的饮食诱导肾功能衰竭 4 周。将小鼠随机分为三组:对照组、CKD 组和 CKD+FMT 组。4 周后,CKD 小鼠接受来自健康小鼠或磷酸盐缓冲液(作为对照)的粪便微生物群移植(FMT)。移植后 3 周,探索肠道微生物群结构、尿毒症毒素血浆浓度和代谢谱。

结果

与 alpha 多样性的增加相关,我们观察到 FMT 治疗后肠道微生物群紊乱明显改善。FMT 进一步降低了 p-对甲酚硫酸盐的积累,改善了葡萄糖耐量。肾功能没有变化。

结论

这些数据表明,FMT 通过对肠道微生物多样性的有益影响,限制了肠道邻苯二酚途径产生的尿毒症毒素的积累。需要进一步研究以调查 FMT 的效率、在 CKD 患者中进行移植的时机和粪便量,以成为一种治疗选择。

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