Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition
Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition
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粪便微生物群移植通过调节免疫细胞功能和肠道微生物群组成控制小鼠慢性肠道炎症
DOI：
10.3390/cells8060517
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发表时间：
2019-06-01
期刊：
影响因子：
6
通讯作者：
Facciotti, Federica
中科院分区：
文献类型：
--
作者：
Burrello, Claudia;Giuffre, Maria Rita;Facciotti, Federica
不同的胃肠道疾病，包括炎症性肠病（IBD），已经与肠道微生物群组成的改变，即生态失调有关。粪便微生物群移植（FMT）被认为是溃疡性结肠炎患者的一种令人鼓舞的治疗方法，主要是由于恢复正常的结果。我们最近发现，FMT在急性实验性结肠炎中的治疗作用与粘膜免疫系统和肠道微生物群组成的功能调节有关。在这里，我们分析了在慢性实验性结肠炎（一种与IBD患者更相似的疾病）期间，FMT治疗性给药对免疫介导的粘膜炎症途径的影响。将来自生物量正常供体的粘液和粪便经口给予患有葡聚糖硫酸钠（DSS）诱导的慢性结肠炎的小鼠。免疫表型和功能的浸润结肠免疫细胞的细胞荧光分析。通过16S rRNA测序分析肠道微生物组的组成差异。在经历慢性肠道炎症的小鼠中，治疗性FMT能够通过调节促炎基因、抗菌肽和粘蛋白的表达来减少结肠炎症。先天性和适应性粘膜免疫细胞在FMT处理的小鼠中表现出降低的促炎性特征。最后，恢复正常生物核心生态有助于炎症的解决。因此，FMT能够通过诱导抗炎免疫途径的协同激活来控制慢性肠道实验性结肠炎，在机制上支持了溃疡性结肠炎患者中报道的FMT治疗的积极结果。
Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.