Causative Role of Anoxic Environment in Bacterial Regulation of Human Intestinal Function.

IF 2.3 4区 医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2022-10-01 DOI:10.1007/s12195-022-00735-x
Chengyao Wang, Andrea Cancino, Jasmine Baste, Daniel Marten, Advait Anil Joshi, Amreen Nasreen, Abhinav Bhushan
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引用次数: 1

Abstract

Introduction: Life on Earth depends on oxygen; human tissues require oxygen signaling, whereas many microorganisms, including bacteria, thrive in anoxic environments. Despite these differences, human tissues and bacteria coexist in close proximity to each other such as in the intestine. How oxygen governs intestinal-bacterial interactions remains poorly understood.

Methods: To address to this gap, we created a dual-oxygen environment in a microfluidic device to study the role of oxygen in regulating the regulation of intestinal enzymes and proteins by gut bacteria. Two-layer microfluidic devices were designed using a fluid transport model and fabricated using soft lithography. An oxygen-sensitive material was integrated to determine the oxygen levels. The intestinal cells were cultured in the upper chamber of the device. The cells were differentiated, upon which bacterial strains, a facultative anaerobe, Escherichia coli Nissle 1917, and an obligate anaerobe, Bifidobacterium Adolescentis, were cultured with the intestinal cells.

Results: The microfluidic device successfully established a dual-oxygen environment. Of particular importance in our findings was that both strains significantly upregulated mucin proteins and modulated several intestinal transporters and transcription factors but only under the anoxic-oxic oxygen gradient, thus providing evidence of the role of oxygen on bacterial-epithelial signaling.

Conclusions: Our work that integrates cell and molecular biology with bioengineering presents a novel strategy to engineer an accessible experimental system to provide tailored oxygenated environments. The work could provide new avenues to study intestine-microbiome signaling and intestinal tissue engineering, as well as a novel perspective on the indirect effects of gut bacteria on tissues including tumors.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-022-00735-x.

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缺氧环境在细菌调节人体肠道功能中的作用。
地球上的生命依赖氧气;人体组织需要氧气信号,而许多微生物,包括细菌,在缺氧环境中茁壮成长。尽管存在这些差异,但人体组织和细菌却彼此紧密共存,比如在肠道中。氧气如何控制肠道与细菌的相互作用仍然知之甚少。方法:为了解决这一空白,我们在微流控装置中创建了双氧环境,研究氧在肠道细菌对肠道酶和蛋白质的调节中的作用。采用流体输运模型设计了双层微流体器件,并用软光刻技术制作了双层微流体器件。一种对氧敏感的材料被用来测定氧含量。在装置的上腔中培养肠细胞。细胞分化后,在此基础上,将兼性厌氧菌大肠杆菌(Escherichia coli Nissle 1917)和专性厌氧菌青少年双歧杆菌(Bifidobacterium adolescence)与肠道细胞一起培养。结果:微流控装置成功建立了双氧环境。在我们的发现中特别重要的是,这两种菌株都显著上调粘蛋白并调节几种肠道转运蛋白和转录因子,但仅在缺氧-缺氧梯度下,从而提供了氧气在细菌-上皮信号传导中的作用的证据。结论:我们的工作将细胞和分子生物学与生物工程相结合,提出了一种新的策略来设计一个可访问的实验系统,以提供定制的含氧环境。这项工作可以为研究肠道微生物组信号和肠道组织工程提供新的途径,并为肠道细菌对包括肿瘤在内的组织的间接影响提供新的视角。补充信息:在线版本包含补充资料,提供地址为10.1007/s12195-022-00735-x。
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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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