Biomarker for Ischemic Stroke Using Metabolome: A Clinician Perspective

Evgeny Sidorov,Dharambir K. Sanghera,Jairam K. P. Vanamala 대한뇌졸중학회 2019 Journal of stroke Vol.21 No.1

Finding ischemic stroke biomarker is highly desirable because it can improve diagnosis even before a patient arrives to the hospital. Metabolome is one of new technologies that help to find biomarkers. Most metabolome-related ischemic stroke studies were done in Asia and had exploratory designs. Although failed to find specific biomarkers, they discovered several important metabolite-stroke associations which belong to three pathophysiological mechanisms: Excitotoxicity with activation of glutamate, resulting in the increase of glutamate derivatives proline and pyroglutamate; Oxidative stress with production of free radicals and perturbed concentrations of uric acid, matrix metalloproteinase-9, branch-chained amino acids, sphingolipids, homocysteine, asymmetric dimethylarginine, nitric oxide and folate cycle metabolites; and Stroke mediated inflammation, affecting phospholipid metabolism with perturbed levels of lysophosphatidylethanolamine and lysophosphatidylcholine. The discovered metabolite-stroke associations need further evaluation in prospective, high-quality studies with patients matched for age, risk factors, and medications.

영양 대사체학

홍영식(Young-Shick Hong) 한국식품영양과학회 2014 한국식품영양과학회지 Vol.43 No.2

대사체학이 질병, 약물, 스트레스, 식이, 생활습관, 유전적 차이, 장내 미생물 등에 의해서 발생하는 비정상적인 대사 메커니즘을 규명하고 관련 바이오 마커 발굴에 중요한 역할이 증명됨에 따라, 식품 영양학과 대사체학이 융합된 영양 대사체학의 역할이 더욱 중요해지고 있다. 특히 잘못된 식생활에 따른 미래의 질병 예측이 가능해지고 있어 향후 적절한 질병 예방이나 치료를 위한 적절한 식생활이나 식이에 대한 정보를 제공함으로써 건강 증진은 물론 개인별 맞춤식이나 맞춤약물 처방을 통한 개인 맞춤형 건강관리(personalized health care) 시대가 멀지 않았다. 또한 복잡한 식생활 패턴, 대사 반응에 대한 개인 간 차이 그리고 방대한 대사체 데이터와의 관계들을 효과적으로 밝혀낼 수 있는 기술에 대한 지속적인 개발과 영양 대사체학(nutritional metabolomics)이 유전체학(genomics or transcriptomics)과 단백체학(proteomics) 기술과 융합적으로 연구가 이루어질 때 질병과 식사 섭취 사이의 관계가 더욱 투명하게 규명될 것이다. Metabolomics is the study of changes in the metabolic status of an organism as a consequence of drug treatment, environmental influences, nutrition, lifestyle, genetic variations, toxic exposure, disease, stress, etc, through global or comprehensive identification and quantification of every single metabolite in a biological system. Since most chronic diseases have been demonstrated to be linked to nutrition, nutritional metabolomics has great potential for improving our understanding of the relationship between disease and nutritional status, nutrient, or diet intake by exploring the metabolic effects of a specific food challenge in a more global manner, and improving individual health. In particular, metabolite profiling of biofluids, such as blood, urine, or feces, together with multivariate statistical analysis provides an effective strategy for monitoring human metabolic responses to dietary interventions and lifestyle habits. Therefore, studies of nutritional metabolomics have recently been performed to investigate nutrition-related metabolic pathways and biomarkers, along with their interactions with several diseases, based on animal-, individual-, and population-based criteria with the goal of achieving personalized health care in the future. This article introduces analytical technologies and their application to determination of nutritional phenotypes and nutrition-related diseases in nutritional metabolomics.

The Integral Role and Clinical Significance of Metabolic Profiling in Prostate Cancer: A Narrative Review

Valentin Nikolaevich Pavlov,Marat Fayazovich Urmantsev,Marat Radikovich Bakeev,Olalekan Samuel Akinyemi 대한비뇨기종양학회 2024 Journal of Urologic Oncology Vol.22 No.2

Prostate cancer (PC) is the most commonly diagnosed malignancy among males worldwide. In recent years, there has been a need to find alternative methods for the early diagnosis of PC. Evidence indicates that metabolic dysfunction is a characteristic feature of PC carcinogenesis, with various metabolites acting as biomarkers of tumor growth. Metabolomics is a new science that has emerged at the intersection of molecular biology, biochemistry, and genetics. The complete set of substrates and metabolic products is a metabolic profile, or metabolome. The PC metabolome comprises substances formed as a result of metabolic changes in response to the occurrence of a malignant process in the prostate gland. We have obtained unique data on metabolic changes that allow us to rethink the carcinogenesis of PC. Research on the metabolome opens up new opportunities for the early diagnosis and treatment of PC, with implications for its prognosis.

Report : Analysis of Metabolite Profile Data Using Batch-Learning Self-Organizing Maps

( Jae Kwang Kim ),( Myoung Rae Cho ),( Hyung Jin Baek ),( Tae Hun Ryu ),( Chang Yeon Yu ),( Myong Jo Kim ),( Eiichiro Fukusaki ),( Akio Kobayashi ) 한국식물학회 2007 Journal of Plant Biology Vol.50 No.4

Novel tools are needed for efficient analysis and visualization of the massive data sets associated with metabolomics. Here, we describe a batch-learning self-organizing map (BL-SOM) for metabolome informatics that makes the learning process and resulting map independent of the order of data input. This approach was successfully used in analyzing and organizing the metabolome data for Arabidopsis thaliana cells cultured under salt stress. Our 6 × 4 matrix presented patterns of metabolite levels at different time periods. A negative correlation was found between the levels of amino acids and metabolites related to glycolysis metabolism in response to this stress. Therefore, BL-SOM could be an excellent tool for clustering and visualizing high dimensional, complex metabolome data in a single map.

Can Food Factors Provide Us with the Similar Beneficial Effects of Physical Exercise?

Licht Miyamoto 한국식품과학회 2016 Food Science and Biotechnology Vol.25 No.suppl1

Metabolic diseases have got global health issues. Physical exercise as well as diet therapy is a potent strategy for fighting against the diseases. However, it is often difficult to continue to keep exercise regularly enough to take sufficient effect. Thus, good substitutes for the therapeutic exercise would be greatly beneficial. Recent studies have suggested that 5'AMP-activated protein kinase (AMPK) play important roles in the metabolic alterations by muscle contraction. The notion that AMPK mediates broad effects of physical exercise has been widely accepted, though it has been challenged by observations in some genetically AMPK-disrupted animals. We have demonstrated metabolome-wide significance of AMPK activation in contracting muscles. Thus, pharmacological activation of AMPK can be a promising way to obtain similar effects of the exercise. The relevance of AMPK will be introduced, and possible strategies for obtaining similar effects to the exercise from food factors will be discussed in the current review.

Culture Medium Profiling and Design Assisted by Machine Learning

Massaki KONISHI 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Production media for microbial cultivation is a significant factor to perform efficient cell growth and production. In industrial fermentation processes, raw materials including yeast, malt, and meat extracts, peptone, molasses, and the other agricultural and industrial waste are often used. The compositions can be varied in seasonal and geological varieties, brands, and production-lots, and influence microbial growth and material production. To understand the varieties of medium components, we have suggested that an analytical method assisted by metabolomics-like finger printing using gas-chromatogram mass spectrometry (Tachibana et al. 2019), and by deep neural networks (DNN) architecture (Tachibana et al. 2021) can apply to culture medium profiling. In the study, it was analyzed as a typical microbial cultivation that various brands of yeast extract were influenced to Escherichia coli growth and green fluorescent protein (GFP), a model of foreign protein production. According to our procedure, the bacterial growth and protein production was accurately estimated from the initial medium components profiles measured by GC-MS. Furthermore, significant components were estimated by a permutation algorithm using DNN model. The results indicated that the initial medium components can sufficiently explain the cultivation results including growth and protein production. As well, bioethanol production can be explained by the composition of toxic materials in lignocellulosic hydrolysates (Watanabe et al. 2019; Konishi 2020). To design optimal culture medium for engineered E. coli producing GFP, L81 Latin square design with 3 levels was applied to minimal medium M9 with supplemental components including amino acids and vitamins. To compare suitable machine learning algorithms for estimating GFP production, 12 algorithms, linear regression (LR), Ridge regression (Ridge), Lasso regression (Lasso), support vector machine (SVM), partial least square regression (PLS), decision tree regression (dtree), random forest regression (RFR), neural networks (NN), deep neural networks (DNN), Gradient tree boosting regression (gbr), K neighbor regression (kbr), and voting regression (vtr) were applied. According to evaluate the algorithms by cross validation (supervised: 85% and validation: 15%), although mean square errors between measured and estimated values of test data (MSEtest) were approximately 1.0-1.5 in case of LR, Ridge, Lasso, SVM, and PLS, those of dtree, RFR, gbr, NN, and DNN were in range below 0.06. On the other hand, considering interaction terms of independent variables, the data accurately fit to the all tested algorithms. The MSEtest were in range between 0.03 and 0.07. The results meant that interaction among medium components were strongly influenced to GFP production. Gaussian process optimization using trained DNN model as objective function were applied to exploring the optimal medium composition for GFP production. Based on the experimental confirmation, the improved composition increased GFP fluorescence to 117% against the best in the original experimental dataset in fact. The machine-learning-associated optimization of culture medium can provide high-throughput explore of the optimal medium compositions for not only microbial culture but also mammalian culture in theoretically. Furthermore, the idea will contribute to promote digital transformation for wide range of bioproductions. This research was partly supported by New Energy and Industrial Technology Development Organization (NEDO) project of Ministry of Economy, Trade and Industry (METI), Japan.

Omics in gut microbiome analysis

원태웅,Shin Na-Ri,Kim Joon Yong,Roh Seong Woon 한국미생물학회 2021 The journal of microbiology Vol.59 No.3

Our understanding of the interactions between microbial communities and their niche in the host gut has improved owing to recent advances in environmental microbial genomics. Integration of metagenomic and metataxonomic sequencing data with other omics data to study the gut microbiome has become increasingly common, but downstream analysis after data integration and interpretation of complex omics data remain challenging. Here, we review studies that have explored the gut microbiome signature using omics approaches, including metagenomics, metataxonomics, metatranscriptomics, and metabolomics. We further discuss recent analytics programs to analyze and integrate multi-omics datasets and further utilization of omics data with other advanced techniques, such as adaptive immune receptor repertoire sequencing, microbial culturomics, and machine learning, to evaluate important microbiome characteristics in the gut.

대사체학의 연구 동향, 응용 및 국내 연구 활성화 방안

김소현,양승옥,김경헌,김영석,유광현,윤영란,이동호,이충환,황금숙,정면우,최기환,최형균,Kim, So-Hyun,Yang, Seung-Ok,Kim, Kyoung-Heon,Kim, Young-Suk,Liu, Kwang-Hyeon,Yoon, Young-Ran,Lee, Dong-Ho,Lee, Choong-Hwan,Hwang, Geum-Sook,Chung, Myeon 한국생물공학회 2009 KSBB Journal Vol.24 No.2

대사체학은 동 식물, 미생물뿐만 아니라 식품, 농업, 의약품에 이르기까지 다양한 분야에서 적용될 수 있으며, 최근 미래를 선도할 학문으로서 주목 받고 있는 분야이다. 하지만 우리나라의 대사체학 연구는 아직 기초적 단계이며, 대사체학에 대한 인식도 부족한 상황이다. 따라서 본 논문에서는 대사체 연구 방법에 대해서 간단히 소개하였고, 국내 외 대사체학 연구현황, 대사체 연구의 필요성과 활용방안, 대사체 연구 수행 활성화를 위한 전략들을 소개하였다. 대사체학은 활용 범위가 매우 넓은 것이 특징인데, 예를 들어 functional genomics, 생물의 계통 분류, 생물의 대사경로 규명, 생물을 이용한 유용물질 생산, 신약 및 신소재 개발, biomarker의 개발, 식품 및 천연물 제제의 품질관리, 그리고 환경 및 독성 모니터링 등에 활용될 수 있다. 그러나 국내 대사체학 연구는 초기단계에 머물러 있는 실정이므로 국내 대사체 연구의 발전을 위해서는 연구 주체간의 협력, 해외 선진 기술 습득, 연구 개발 투자, 대사체 분석 전문가 육성, metabolome database 구축 등이 필요하다. 대사체학 연구에 대한 이러한 지원이 이뤄진다면, 대사체학 분야에 있어서 국내수준과 세계수준의 격차는 줄어들 것이다. 또한 결과적으로 대사체학 연구의 발전은 한국 생명공학 분야 (BT)의 발전에도 크게 이바지할 것으로 사료된다. As one of the new areas of 'omics' technology, there is increasing interest in metabolomics, which involves the analysis of low-molecular-weight compounds in cells, tissues, and biofluids, and considers interactions within various organisms and reactions of external chemicals with those organisms. However, metabolomics research is still at a fundamental stage in Korea. Therefore, the purpose of this study was to establish a strategic long-term plan to revitalize the national metabolomics approach and obtain the elementary data necessary to determine a policy for effectively supporting metabolomics research. These investigations clarified the state of metabolomics study both in Korea and internationally, from which we attempted to find the potentiality and fields where a metabolomics approach would be applicable, such as in medical science. We also discuss strategies for developing metabolomics research. This study revealed that promoting metabolomics in Korea requires cooperation with metabolomics researchers, acquisition of advanced technology, capital investment in metabolomics approach, establishment of metabolome database, and education of metabolome analysis experts. This would reduce the gap between the national and international levels of metabolomics research, with the resulting developments in metabolomics having the potential to greatly contribute to promoting biotechnology in Korea.

High Plasticity of the Gut Microbiome and Muscle Metabolome of Chinese Mitten Crab (Eriocheir sinensis) in Diverse Environments

( Xiaowen Chen ),( Haihong Chen ),( Qinghua Liu ),( Kangda Ni ),( Rui Ding ),( Jun Wang ),( Chenghui Wang ) 한국미생물생명공학회(구 한국산업미생물학회) 2021 Journal of microbiology and biotechnology Vol.31 No.2

Phenotypic plasticity is a rapid response mechanism that enables organisms to acclimate and survive in changing environments. The Chinese mitten crab (Eriocheir sinensis) survives and thrives in different and even introduced habitats, thereby indicating its high phenotypic plasticity. However, the underpinnings of the high plasticity of E. sinensis have not been comprehensively investigated. In this study, we conducted an integrated gut microbiome and muscle metabolome analysis on E. sinensis collected from three different environments, namely, an artificial pond, Yangcheng Lake, and Yangtze River, to uncover the mechanism of its high phenotypic plasticity. Our study presents three divergent gut microbiotas and muscle metabolic profiles that corresponded to the three environments. The composition and diversity of the core gut microbiota (Proteobacteria, Bacteroidetes, Tenericutes, and Firmicutes) varied among the different environments while the metabolites associated with amino acids, fatty acids, and terpene compounds displayed significantly different concentration levels. The results revealed that the gut microbiome community and muscle metabolome were significantly affected by the habitat environments. Our findings indicate the high phenotypic plasticity in terms of gut microbiome and muscle metabolome of E. sinensis when it faces environmental changes, which would also facilitate its acclimation and adaptation to diverse and even introduced environments.

A Pilot Study Exploring Temporal Development of Gut Microbiome/Metabolome in Breastfed Neonates during the First Week of Life

Imad Awan,Emily Schultz,John D. Sterrett,Lamya’a M. Dawud,Lyanna R. Kessler,Deborah Schoch,Christopher A. Lowry,Lori Feldman-Winter,Sangita Phadtare 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.2

Purpose: Exclusive breastfeeding promotes gut microbial compositions associated with lower rates of metabolic and autoimmune diseases. Its cessation is implicated in increased microbiome-metabolome discordance, suggesting a vulnerability to dietary changes. Formula supplementation is common within our low-income, ethnic-minority community. We studied exclusively breastfed (EBF) neonates’ early microbiome-metabolome coupling in efforts to build foundational knowledge needed to target this inequality. Methods: Maternal surveys and stool samples from seven EBF neonates at first transitional stool (0–24 hours), discharge (30–48 hours), and at first appointment (days 3–5) were collected. Survey included demographics, feeding method, medications, medical history and tobacco and alcohol use. Stool samples were processed for 16S rRNA gene sequencing and lipid analysis by gas chromatography-mass spectrometry. Alpha and beta diversity analyses and Procrustes randomization for associations were carried out. Results: Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were the most abundant taxa. Variation in microbiome composition was greater between individuals than within (p=0.001). Palmitic, oleic, stearic, and linoleic acids were the most abundant lipids. Variation in lipid composition was greater between individuals than within (p=0.040). Multivariate composition of the metabolome, but not microbiome, correlated with time (p=0.030). Total lipids, saturated lipids, and unsaturated lipids concentrations increased over time (p=0.012, p=0.008, p=0.023). Alpha diversity did not correlate with time (p=0.403). Microbiome composition was not associated with each samples’ metabolome (p=0.450). Conclusion: Neonate gut microbiomes were unique to each neonate; respective metabolome profiles demonstrated generalizable temporal developments. The overall variability suggests potential interplay between influences including maternal breastmilk composition, amount consumed and living environment.