Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice.

Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice.
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高脂饮食喂养小鼠益生菌介导的代谢综合征减轻过程中肠道微生物群的调节。

DOI:
10.1038/ismej.2014.99
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发表时间:
2015-01
期刊:
The ISME journal
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其他
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肠道微生物区系结构紊乱和相关炎症被认为是高脂饮食(HFD)诱导代谢综合征(MS)的重要病因。3株候选益生菌:副乳杆菌CNCM I-4270(LC)、鼠李糖乳杆菌I-3690(LR)和动物双歧杆菌亚种。Lacs I-2494(BA)分别给高脂饲料喂养的小鼠(108 细胞, day−1)灌胃12周。各菌株均可减轻体重增加和巨噬细胞向附睾脂肪组织的渗透,并显著改善葡萄糖-胰岛素稳态和肝脏脂肪变性。基于粪便细菌16S rRNA基因454焦解测序的加权UniFrac主坐标分析表明,益生菌使HFD破坏的肠道微生物区系的整体结构向喂食正常饮食的瘦小鼠倾斜。冗余度分析表明,益生菌改变了83个操作分类单位(OTU)的丰度。49个改变的OTUS与一个或多个寄主MS参数显著相关,并被指定为“功能相关的系统型”。在15个与MS表型负相关的功能相关OTU中有13个被促进,而在34个与MS正相关的OTU中有26个被至少一种益生菌减少,但每个菌株改变了一组不同的功能相关OTU。LC和LR可增加盲肠乙酸盐的表达,但不影响循环脂多糖结合蛋白;相反,BA不增加乙酸盐,但显著降低脂肪和肝脏肿瘤坏死因子-α基因的表达。这些结果表明,乳杆菌和双歧杆菌在一定程度上通过菌株特异性影响小鼠肠道微生物区系的MS相关系统型,从而不同地减轻肥胖共病。
Structural disruption of gut microbiota and associated inflammation are considered important etiological factors in high fat diet (HFD)-induced metabolic syndrome (MS). Three candidate probiotic strains, Lactobacillus paracasei CNCM I-4270 (LC), L. rhamnosus I-3690 (LR) and Bifidobacterium animalis subsp. lactis I-2494 (BA), were individually administered to HFD-fed mice (108 cells day−1) for 12 weeks. Each strain attenuated weight gain and macrophage infiltration into epididymal adipose tissue and markedly improved glucose–insulin homeostasis and hepatic steatosis. Weighted UniFrac principal coordinate analysis based on 454 pyrosequencing of fecal bacterial 16S rRNA genes showed that the probiotic strains shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean mice fed a normal (chow) diet. Redundancy analysis revealed that abundances of 83 operational taxonomic units (OTUs) were altered by probiotics. Forty-nine altered OTUs were significantly correlated with one or more host MS parameters and were designated ‘functionally relevant phylotypes'. Thirteen of the 15 functionally relevant OTUs that were negatively correlated with MS phenotypes were promoted, and 26 of the 34 functionally relevant OTUs that were positively correlated with MS were reduced by at least one of the probiotics, but each strain changed a distinct set of functionally relevant OTUs. LC and LR increased cecal acetate but did not affect circulating lipopolysaccharide-binding protein; in contrast, BA did not increase acetate but significantly decreased adipose and hepatic tumor necrosis factor-α gene expression. These results suggest that Lactobacillus and Bifidobacterium differentially attenuate obesity comorbidities in part through strain-specific impacts on MS-associated phylotypes of gut microbiota in mice.
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