Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes
Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes
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DOI：
10.1136/gutjnl-2019-320118
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发表时间：
2020-10-01
期刊：
影响因子：
24.5
通讯作者：
Kovacs, Peter
中科院分区：
文献类型：
--
作者：
Massier, Lucas;Chakaroun, Rima;Kovacs, Peter
目的由于肠道通透性增加，细菌移位到包括人类脂肪组织(AT)在内的各种器官的机制尚不清楚。我们假设：(1)细菌的存在具有高度的组织特异性，(2)细菌的组成和数量与免疫、炎症和代谢负担有关。设计：我们对75例肥胖伴或不伴2型糖尿病(T2D)患者的血液和AT样本(大网膜、肠系膜和皮下)中细菌16S rRNA基因进行了定量和测序，并用催化报告沉积(CARD)-荧光原位杂交(FISH)检测AT中的细菌。结果在严格的实验和生物信息学控制下，在血液和大网膜、皮下和肠系膜AT样品中检测到细菌DNA，范围为0.1~5pg/mgDNA分离物。此外，CARD-FISH可以检测到AT携带的活细菌。变形杆菌和细菌是主要的门，细菌数量以组织特异性的方式与免疫细胞渗透、炎症和代谢参数相关。在患有和不患有T2D的受试者中，细菌组成不同，并与相关的临床措施有关，包括全身和组织特异性炎症标志物。最后，在体外用细菌DNA处理脂肪细胞可以刺激TNFAs和IL6的表达。结论我们的研究为肥胖和T2D的几种AT中细菌和细菌DNA的存在提供了污染意识的证据，并提示细菌在启动和维持局部AT亚临床炎症从而影响肥胖的代谢后遗症中起着重要作用。
Objective Bacterial translocation to various organs including human adipose tissue (AT) due to increased intestinal permeability remains poorly understood. We hypothesised that: (1) bacterial presence is highly tissue specific and (2) related in composition and quantity to immune inflammatory and metabolic burden. Design We quantified and sequenced the bacterial 16S rRNA gene in blood and AT samples (omental, mesenteric and subcutaneous) of 75 subjects with obesity with or without type 2 diabetes (T2D) and used catalysed reporter deposition (CARD) - fluorescence in situ hybridisation (FISH) to detect bacteria in AT. Results Under stringent experimental and bioinformatic control for contaminants, bacterial DNA was detected in blood and omental, subcutaneous and mesenteric AT samples in the range of 0.1 to 5 pg/mu g DNA isolate. Moreover, CARD-FISH allowed the detection of living, AT-borne bacteria.ProteobacteriaandFirmicuteswere the predominant phyla, and bacterial quantity was associated with immune cell infiltration, inflammatory and metabolic parameters in a tissue-specific manner. Bacterial composition differed between subjects with and without T2D and was associated with related clinical measures, including systemic and tissues-specific inflammatory markers. Finally, treatment of adipocytes with bacterial DNA in vitro stimulated the expression ofTNFAandIL6. Conclusions Our study provides contaminant aware evidence for the presence of bacteria and bacterial DNA in several ATs in obesity and T2D and suggests an important role of bacteria in initiating and sustaining local AT subclinical inflammation and therefore impacting metabolic sequelae of obesity.