Spatial Metabolomics: Revolutionizing Food, Medicine Research

Tsinghua University Press

Spatial metabolomics, as an emerging interdisciplinary field deeply integrating metabolomics with spatial analysis technologies, is fundamentally transforming our comprehension of metabolic networks within organisms. By retaining the original spatial distribution information of metabolites in tissues, it achieves a cognitive leap from "identifying what exists" to "pinpointing where it occurs." In the realm of plant science, this technology has been employed to elucidate three-dimensional distribution maps of bioactive components across distinct tissue regions of medicinal plants. With sustained technological innovations, the global market for spatial metabolomics analysis services is expanding at an 8.7% compound annual growth rate (CAGR), projected to reach $348 million by 2031, with China's market exhibiting particularly notable growth momentum.

"Medicinal and Edient Homology," a core tenet of traditional Chinese medicine (TCM) philosophy, derives its material foundation from the synergistic effects of multi-component systems. A single medicinal herb or food often contains tens to hundreds of bioactive constituents—such as flavonoids, organic acids, and polysaccharides in hawthorn, which collectively constitute its chemical basis for lipid-lowering and digestive functions. Upon entering biological systems, these components undergo intricate absorption-distribution-metabolism-excretion (ADME) processes, interacting with intestinal microbiota, enzymatic systems, and multi-organ targets to form dynamic metabolic networks. Current research confronts three principal challenges:

First, the "black box" of component interactions persists. Traditional metabolomics evaluates holistic effects through metabolite profiling in blood or urine but struggles to localize in situ targets of specific components within organs or cellular substructures. Second, the spatiotemporal dynamics of medicinal and edient substances remain poorly characterized. Their efficacy exhibits temporal accumulation and spatial specificity, yet conventional methods lack the resolution to capture these dimensions. Third, the environment-substance-organism triadic relationship demands exploration. Specialized environments (e.g., high-altitude hypoxia) induce plants to synthesize unique components (e.g., salidroside in Rhodiola), which in turn enhance organismal adaptability to such environments. The mechanistic transmission of these environmental imprints urgently requires validation at the spatial metabolic level.

Leveraging its advantages in in situ analysis and high-resolution visualization, spatial metabolomics provides revolutionary tools to address these challenges. Its applications converge on three strategic directions:First, unraveling the spatiotemporal trajectories of multi-components in vivo. Through mass spectrometry imaging (MSI), the distribution and transformation pathways of medicinal and edient substances can be visually mapped across biological systems. This "component-absorption site-target organ" full-chain tracing will offer precise guidance for optimizing product efficacy. When integrated with artificial intelligence (AI) algorithms for multi-dimensional data mining, it enables the establishment of quantitative structure-activity relationships (QSAR) between spatial metabolite distributions and bioactivities, propelling formula design from empirical combinations to data-driven predictions. Second, elucidating metabolic interactions in intestinal microdomains. The intestine serves as a critical action site for medicinal and edient substances. By combining spatial metabolomics with laser capture microdissection, researchers can perform in situ analysis of microbial metabolic microenvironments across intestinal zones (e.g., crypts, villus tips, Peyer's patches), thereby uncovering direct evidence of "component-microbiota-host" tripartite dialogues. Third, guiding the geo-authentic evaluation of medicinal materials. The efficacy of medicinal and edient substances is closely tied to their growth environment (geo-authenticity). Spatial metabolomics facilitates the construction of correlation models linking "environmental factors-component spatial patterns-efficacy intensity," thereby providing objective chemical markers for geo-authenticity authentication.

Despite its vast potential, the industrialization of spatial metabolomics in the medicinal and edient field faces practical challenges. High detection costs (The $3,000–$5,000 per sample) limit large-scale applications; plant tissue matrix effects interfere with imaging accuracy; and standardized protocols for multi-omics data integration remain lacking. Nevertheless, promising solutions are emerging: the development of specialized plant sample preparation protocols (e.g., biodegradable matrix coatings), the promotion of domestically produced high-resolution mass spectrometry imaging devices to reduce costs, the establishment of spatial metabolome databases for medicinal and edient components to enable data sharing, and the formulation of industry technical guidelines and standards to streamline data acquisition and analysis workflows.

In summary, spatial metabolomics is spearheading a revolutionary transition in medicinal and edient research from "macroscopic holistic effect evaluation" to "microscopic spatial resolution." Through synergistic innovations in AI-assisted image recognition, ultra-sensitive probe labeling, and in situ metabolic flux analysis, three breakthroughs are anticipated: 1) the creation of the first human spatial metabolome atlas for medicinal and edient components; 2) the development of personalized dietary recommendation systems based on spatial metabolic profiles; and 3) the invention of environment-responsive smart cultivation technologies to directionally enrich bioactive compounds. Aligning with the "Healthy China 2030" initiative's emphasis on leveraging TCM's unique advantages and modernizing its practices, spatial metabolomics will provide pivotal technological support to advance medicinal and edient substances from traditional empiricism to precision science, ultimately realizing the vision of "optimizing food utility and maximizing medicinal efficacy." In domains such as geo-authenticity evaluation, active constituent identification, and personalized interventions, this technology will empower China's medicinal and edient industry to seize global health innovation leadership, rejuvenating millennia-old wisdom for contemporary well-being.

About the Author

Boran Zhu is a researcher at Nanjing University of Chinese Medicine, a recipient of the Jiangsu Provincial Young Science and Technology Talent Support Program, and the Standing Director of the Jiangsu Association of Medicated Diet. He serves as a Youth Editorial Board Member for journals including Journal of Future Foods, Traditional Medicine Research, and Food & Medicine Homology, and as a reviewer for several SCI journals such as Advanced Science, Phytomedicine, and npj Science of Food. He has presided over 7 research projects, including those funded by the National Natural Science Foundation of China(NSFC). His main research focuses on basic research of heart and brain diseases in traditional Chinese medicine, modern biological studies on diet and health, and the application of small molecule imaging technology in TCM research.

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