Mapping the influence of the gut microbiota on small molecules in the brain through mass spectrometry imaging
Mapping the influence of the gut microbiota on small molecules in the brain through mass spectrometry imaging
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DOI：
10.1101/2020.03.13.987164
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发表时间：
2020-03
期刊：
影响因子：
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通讯作者：
Heather Hulme;Lynsey M. Meikle;Nicole Strittmatter;J. Swales;G. Hamm;S. Brown;S. Milling;A. MacDonald;R. Goodwin;R. Burchmore;D. Wall
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文献类型：
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作者：
Heather Hulme;Lynsey M. Meikle;Nicole Strittmatter;J. Swales;G. Hamm;S. Brown;S. Milling;A. MacDonald;R. Goodwin;R. Burchmore;D. Wall
背景肠道微生物区系几乎影响人类健康的方方面面。最近的工作强调了肠道微生物区系通过微生物组-肠道-脑轴在神经健康中的潜在作用。微生物可以直接或间接地影响大脑；通过神经递质的产生，宿主免疫调节剂的诱导，或通过释放或诱导其他微生物或宿主分子。方法在这里，我们使用质谱学成像(MSI)，一种无标记的成像工具，来描绘在无菌、抗生素治疗和对照的小鼠的肠道和大脑中发生的分子变化。结果我们确定了神经递质及其前体在脑和肠道切片上的空间分布和相对定量。利用小分子的非靶向MSI，我们检测到与对照组相比，无菌动物大脑中四种已鉴定代谢物的水平发生了显著变化：维生素B5、3-羟基-3-甲基戊二酸、3-甲基-4-(三甲基氨基)丁酸和4-(三甲基氨基)戊酸。然而，抗生素治疗在治疗一周后没有引起大脑中这些代谢物的显著变化。结论MSI可用于确定肠道和脑中细菌和宿主代谢物的空间分布和定量，同时也为发现微生物-肠道-脑轴通讯的新媒介提供了可能性。
Background The gut microbiota is known to influence virtually all facets of human health. Recent work has highlighted a potential role for the gut microbiota in neurological health through the microbiome-gut-brain axis. Microbes can influence the brain both directly and indirectly; through neurotransmitter production, induction of host immunomodulators, or through the release or induction of other microbial or host molecules. Methods Here we used mass spectrometry imaging (MSI), a label-free imaging tool, to map the molecular changes that occur in the murine gut and brain in germ-free, antibiotic-treated and control mice. Results We determined the spatial distribution and relative quantification of neurotransmitters and their precursors across brain and gut sections in response to the microbiome. Using untargeted MSI of small molecules, we detected a significant change in the levels of four identified metabolites in the brains of germ-free animals compared to controls; vitamin B5, 3-hydroxy-3-methylglutaric acid, 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate. However, antibiotic treatment induced no significant changes in these metabolites in the brain after one week of treatment. Conclusions This work exemplifies the utility of MSI as a tool in determining the spatial distribution and quantification of bacterial and host metabolites in the gut and brain whilst also offering the potential for discovery of novel mediators of microbiome-gut-brain axis communication.