Gut microbiota in a mouse model of obesity and peripheral neuropathy associated with plasma and nerve lipidomics and nerve transcriptomics.
Gut microbiota in a mouse model of obesity and peripheral neuropathy associated with plasma and nerve lipidomics and nerve transcriptomics.
复制标题
DOI：
10.1186/s40168-022-01436-3
复制
发表时间：
2023-03-15
期刊：
影响因子：
15.5
通讯作者：
中科院分区：
文献类型：
--
作者：
周围神经病变（PN）是肥胖、糖尿病前期和2型糖尿病的常见并发症，但其发病机制仍不完全清楚。在PN的小鼠高脂饮食（HFD）肥胖模型中，饮食逆转（HFD-R）至低脂标准饮食（SD）使神经功能和神经脂质组恢复正常。由于肠道微生物组代表了膳食脂肪摄入与神经健康之间的潜在联系，因此目前的研究通过16 S rRNA分析评估了各种肠道生态位中饮食逆转（HFD-R）范式期间微生物组群落结构的变化。膳食脂肪含量（HFD与SD）也与肠道植物群和代谢及PN表型相关。最后，PN相关的微生物类群，与血浆和坐骨神经脂质组和神经转录组被用来确定脂质物种和基因密切相关的PN表型。相对于SD，HFD中的微生物组结构发生了改变，但HFD-R迅速逆转。与代谢健康正相关的特定类群变体与PN负相关，而与代谢健康负相关的特定类群与PN正相关。在HFD中，PN相关的类群变体，包括乳杆菌属、毛梭菌属和Anaerotruncus，也与几种脂质物质呈正相关，尤其是血浆鞘磷脂和坐骨神经甘油三酯升高。负相关，另外存在与其他类群的变种。此外，特定PN相关类群变体和坐骨神经转录组之间出现的关系与炎症，脂质代谢和抗氧化防御途径有关，这些都是在PN发病机制中建立的。目前的结果表明，HFD改变了微生物组结构，某些分类群变体与代谢健康和PN相关。PN相关分类群与某些脂质种类和神经转录组相关通路之间的明显联系还为微生物群的新靶点和PN中相关的潜在作用机制提供了深入了解。因此，这些发现加强了PN中肠道微生物组-外周神经系统特征的可能性，并支持继续研究，重点是定义肠道微生物组和神经健康之间的联系，以提供机制见解和治疗机会。视频摘要在线版本包含补充材料，可通过10. 1186/s40168-022-01436-3获取。
Peripheral neuropathy (PN) is a common complication in obesity, prediabetes, and type 2 diabetes, though its pathogenesis remains incompletely understood. In a murine high-fat diet (HFD) obesity model of PN, dietary reversal (HFD-R) to a low-fat standard diet (SD) restores nerve function and the nerve lipidome to normal. As the gut microbiome represents a potential link between dietary fat intake and nerve health, the current study assessed shifts in microbiome community structure by 16S rRNA profiling during the paradigm of dietary reversal (HFD-R) in various gut niches. Dietary fat content (HFD versus SD) was also correlated to gut flora and metabolic and PN phenotypes. Finally, PN-associated microbial taxa that correlated with the plasma and sciatic nerve lipidome and nerve transcriptome were used to identify lipid species and genes intimately related to PN phenotypes. Microbiome structure was altered in HFD relative to SD but rapidly reversed with HFD-R. Specific taxa variants correlating positively with metabolic health associated inversely with PN, while specific taxa negatively linked to metabolic health positively associated with PN. In HFD, PN-associated taxa variants, including Lactobacillus, Lachnoclostridium, and Anaerotruncus, also positively correlated with several lipid species, especially elevated plasma sphingomyelins and sciatic nerve triglycerides. Negative correlations were additionally present with other taxa variants. Moreover, relationships that emerged between specific PN-associated taxa variants and the sciatic nerve transcriptome were related to inflammation, lipid metabolism, and antioxidant defense pathways, which are all established in PN pathogenesis. The current results indicate that microbiome structure is altered with HFD, and that certain taxa variants correlate with metabolic health and PN. Apparent links between PN-associated taxa and certain lipid species and nerve transcriptome-related pathways additionally provide insight into new targets for microbiota and the associated underlying mechanisms of action in PN. Thus, these findings strengthen the possibility of a gut-microbiome-peripheral nervous system signature in PN and support continuing studies focused on defining the connection between the gut microbiome and nerve health to inform mechanistic insight and therapeutic opportunities. Video Abstract The online version contains supplementary material available at 10.1186/s40168-022-01436-3.
登录
查看更多内容
影响因子：
5.9
作者：
Hasain Z;Raja Ali RA;Ahmad HF;Abdul Rauf UF;Oon SF;Mokhtar NM
通讯作者：
Mokhtar NM
影响因子：
5.5
作者：
Hernandez-Baixauli J;Puigbò P;Torrell H;Palacios-Jordan H;Ripoll VJR;Caimari A;Del Bas JM;Baselga-Escudero L;Mulero M
通讯作者：
Mulero M
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
81.5
作者：
Feldman, Eva L.;Callaghan, Brian C.;Viswanathan, Vijay
通讯作者：
Viswanathan, Vijay
DOI：
10.1099/ijsem.0.004283
发表时间：
2020-01-01
影响因子：
2.8
作者：
Flaiz, Maximilian;Baur, Tina;Bengelsdorf, Frank R.
通讯作者：
Bengelsdorf, Frank R.