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Advances in functional analysis of the microbiome: Integrating metabolic modeling, metabolite prediction, and pathway inference with Next-Generation Sequencing data
Sungwon Jung
J. Microbiol. 2025;63(1):e.2411006.   Published online January 24, 2025
DOI: https://doi.org/10.71150/jm.2411006
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  • 71 Download
AbstractAbstract PDF

This review explores current advancements in microbiome functional analysis enabled by next-generation sequencing technologies, which have transformed our understanding of microbial communities from mere taxonomic composition to their functional potential. We examine approaches that move beyond species identification to characterize microbial activities, interactions, and their roles in host health and disease. Genome-scale metabolic models allow for in-depth simulations of metabolic networks, enabling researchers to predict microbial metabolism, growth, and interspecies interactions in diverse environments. Additionally, computational methods for predicting metabolite profiles offer indirect insights into microbial metabolic outputs, which is crucial for identifying biomarkers and potential therapeutic targets. Functional pathway analysis tools further reveal microbial contributions to metabolic pathways, highlighting alterations in response to environmental changes and disease states. Together, these methods offer a powerful framework for understanding the complex metabolic interactions within microbial communities and their impact on host physiology. While significant progress has been made, challenges remain in the accuracy of predictive models and the completeness of reference databases, which limit the applicability of these methods in under-characterized ecosystems. The integration of these computational tools with multi-omic data holds promise for personalized approaches in precision medicine, allowing for targeted interventions that modulate the microbiome to improve health outcomes. This review highlights recent advances in microbiome functional analysis, providing a roadmap for future research and translational applications in human health and environmental microbiology.

Journal Articles
Intervention with kimchi microbial community ameliorates obesity by regulating gut microbiota
Seong-Eun Park , Sun Jae Kwon , Kwang-Moon Cho , Seung-Ho Seo , Eun-Ju Kim , Tatsuya Unno , So-Hyeon Bok , Dae-Hun Park , Hong-Seok Son
J. Microbiol. 2020;58(10):859-867.   Published online September 2, 2020
DOI: https://doi.org/10.1007/s12275-020-0266-2
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  • 19 Web of Science
  • 19 Crossref
AbstractAbstract
The objective of this study was to evaluate anti-obesity effects of kimchi microbial community (KMC) on obesity and gut microbiota using a high fat diet-induced mouse model compared to effects of a single strain. Administration of KMC decreased body weight, adipose tissue, and liver weight gains. Relative content of Muribaculaceae in the gut of the KMCtreated group was higher than that in the high-fat diet (HFD) group whereas relative contents of Akkermansiaceae, Coriobacteriaceae, and Erysipelotrichaceae were lower in KMCtreated group. Metabolic profile of blood was found to change differently according to the administration of KMC and a single strain of Lactobacillus plantarum. Serum metabolites significantly increased in the HFD group but decreased in the KMC-treated group included arachidic acid, stearic acid, fumaric acid, and glucose, suggesting that the administration of KMC could influence energy metabolism. The main genus in KMC was not detected in guts of mice in KMC-treated group. Since the use of KMC has advantages in terms of safety, it has potential to improve gut microbial community for obese people.

Citations

Citations to this article as recorded by  
  • Anti-obesogenic effects of plant natural products: A focus on Korean traditional foods
    Gitishree Das, Luis Alfonso Jiménez Ortega, Sandra Gonçalves, J. Basilio Heredia, Maria de Lourdes Gomes Pereira, Anabela Romano, Han-Seung Shin, Jayanta Kumar Patra
    Trends in Food Science & Technology.2024; 148: 104470.     CrossRef
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    Journal of Functional Foods.2024; 112: 105966.     CrossRef
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    Journal of Microbiology and Biotechnology.2024; 34(2): 306.     CrossRef
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    Molecular Nutrition & Food Research.2023;[Epub]     CrossRef
  • Certain Fermented Foods and Their Possible Health Effects with a Focus on Bioactive Compounds and Microorganisms
    Gülsüm Deveci, Elif Çelik, Duygu Ağagündüz, Elena Bartkiene, João Miguel F. Rocha, Fatih Özogul
    Fermentation.2023; 9(11): 923.     CrossRef
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    PeerJ.2023; 11: e15680.     CrossRef
  • Immunomodulatory effects of Companilactobacillus allii WiKim39 and Lactococcus lactis WiKim0124 isolated from kimchi on lipopolysaccharide-induced RAW264.7 cells and dextran sulfate sodium-induced colitis in mice
    Ye-Rang Yun, Moeun Lee, Jung Hee Song, Eun Ji Choi, Ji Yoon Chang
    Journal of Functional Foods.2022; 90: 104969.     CrossRef
  • Interaction between the PNPLA3 Gene and Nutritional Factors on NAFLD Development: The Korean Genome and Epidemiology Study
    Sooyeon Oh, Jooho Lee, Sukyung Chun, Ja-Eun Choi, Mi Na Kim, Young Eun Chon, Yeonjung Ha, Seong-Gyu Hwang, Sang-Woon Choi, Kyung-Won Hong
    Nutrients.2022; 15(1): 152.     CrossRef
  • Acids produced by lactobacilli inhibit the growth of commensal Lachnospiraceae and S24-7 bacteria
    Emma J. E. Brownlie, Danica Chaharlangi, Erin Oi-Yan Wong, Deanna Kim, William Wiley Navarre
    Gut Microbes.2022;[Epub]     CrossRef
  • The Role of Gut Microbiota Modulation Strategies in Obesity: The Applications and Mechanisms
    Lingyue Shan, Akanksha Tyagi, Umair Shabbir, Xiuqin Chen, Selvakumar Vijayalakshmi, Pianpian Yan, Deog-Hwan Oh
    Fermentation.2022; 8(8): 376.     CrossRef
  • Fermented rice bran supplementation ameliorates obesity via gut microbiota and metabolism modification in female mice
    Shiro Tochitani, Yoshiteru Maehara, Takahiro Kawase, Takamitsu Tsukahara, Ryoichi Shimizu, Taizo Watanabe, Kazuo Maehara, Kenji Asaoka, Hideo Matsuzaki
    Journal of Clinical Biochemistry and Nutrition.2022; 70(2): 160.     CrossRef
  • Bifidobacterium longum 070103 Fermented Milk Improve Glucose and Lipid Metabolism Disorders by Regulating Gut Microbiota in Mice
    Tong Jiang, Ying Li, Longyan Li, Tingting Liang, Mingzhu Du, Lingshuang Yang, Juan Yang, Runshi Yang, Hui Zhao, Moutong Chen, Yu Ding, Jumei Zhang, Juan Wang, Xinqiang Xie, Qingping Wu
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  • What Is the Role of Gut Microbiota in Obesity Prevalence? A Few Words about Gut Microbiota and Its Association with Obesity and Related Diseases
    Julita Tokarek, Joanna Gadzinowska, Ewelina Młynarska, Beata Franczyk, Jacek Rysz
    Microorganisms.2021; 10(1): 52.     CrossRef
  • Eating Fermented: Health Benefits of LAB-Fermented Foods
    Vincenzo Castellone, Elena Bancalari, Josep Rubert, Monica Gatti, Erasmo Neviani, Benedetta Bottari
    Foods.2021; 10(11): 2639.     CrossRef
  • Anti-Inflammatory and Immunomodulatory Properties of Fermented Plant Foods
    Roghayeh Shahbazi, Farzaneh Sharifzad, Rana Bagheri, Nawal Alsadi, Hamed Yasavoli-Sharahi, Chantal Matar
    Nutrients.2021; 13(5): 1516.     CrossRef
Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro
San-Ying Wang , Jing Zhang , Xiao-Gang Xu , Hui-Li Su , Wen-Min Xing , Zhong-Shan Zhang , Wei-Hua Jin , Ji-Huan Dai , Ya-Zhen Wang , Xin-Yue He , Chuan Sun , Jing Yan , Gen-Xiang Mao
J. Microbiol. 2020;58(8):716-723.   Published online June 10, 2020
DOI: https://doi.org/10.1007/s12275-020-9528-2
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  • 10 Web of Science
  • 11 Crossref
AbstractAbstract
Human cytomegalovirus (hCMV) is a ubiquitous herpesvirus, which results in the establishment of a latent infection that persists throughout the life of the host and can be reactivated when the immunity is low. Currently, there is no vaccine for hCMV infection, and the licensed antiviral drugs mainly target the viral enzymes and have obvious adverse reactions. Thus, it is important to search for compounds with antihCMV properties. The present study aimed to investigate the suppressive effects of piceatannol on hCMV Towne strain infection and the putative underlying mechanisms using human diploid fibroblast WI-38 cells. Piceatannol supplementation prevented the lytic changes induced by hCMV infection in WI-38 cells. Furthermore, piceatannol suppressed the expression of hCMV immediate-early (IE) and early (E) proteins as well as the replication of hCMV DNA in a dose-dependent manner. Moreover, hCMV-induced cellular senescence was suppressed by piceatannol, as shown by a decline in the senescence-associated β-galactosidase (SA-β-Gal) activity and decreased production of intracellular reactive oxygen species (ROS). p16INK4a, a major senescence-associated molecule, was dramatically elevated by current hCMV infection that was attenuated by pre-incubation with piceatannol in a dose-dependent manner. These results demonstrated that piceatannol suppressed the hCMV infection via inhibition of the activation of p16INK4a and cellular senescence induced by hCMV. Together, these findings indicate piceatannol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection.

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Reviews
[Minireivew]Microbial consortia including methanotrophs: some benefits of living together
Rajendra Singh , Jaewon Ryu , Si Wouk Kim
J. Microbiol. 2019;57(11):939-952.   Published online October 28, 2019
DOI: https://doi.org/10.1007/s12275-019-9328-8
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  • 26 Web of Science
  • 28 Crossref
AbstractAbstract
With the progress of biotechnological research and improvements made in bioprocessing with pure cultures, microbial consortia have gained recognition for accomplishing biological processes with improved effectiveness. Microbes are indispensable tool in developing bioprocesses for the production of bioenergy and biochemicals while utilizing renewable resources due to technical, economic and environmental advantages. They communicate with specific cohorts in close proximity to promote metabolic cooperation. Use of positive microbial associations has been recognized widely, especially in food industries and bioremediation of toxic compounds and waste materials. Role of microbial associations in developing sustainable energy sources and substitutes for conventional fuels is highly promising with many commercial prospects. Detoxification of chemical contaminants sourced from domestic, agricultural and industrial wastes has also been achieved through microbial catalysis in pure and co-culture systems. Methanotrophs, the sole biological sink of greenhouse gas methane, catalyze the methane monooxygenasemediated oxidation of methane to methanol, a high energy density liquid and key platform chemical to produce commodity chemical compounds and their derivatives. Constructed microbial consortia have positive effects, such as improved biomass, biocatalytic potential, stability etc. In a methanotroph- heterotroph consortium, non-methanotrophs provide key nutrient factors and alleviate the toxicity from the culture. Non-methanotrophic organisms biologically stimulate the growth and activity of methanotrophs via production of growth stimulators. However, methanotrophs in association with cocultured microorganisms are in need of further exploration and thorough investigation to study their interaction mode and application with improved effectiveness.

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REVIEW] Production of cross-kingdom oxylipins by pathogenic fungi: An update on their role in development and pathogenicity
Gregory J. Fischer , Nancy P. Keller
J. Microbiol. 2016;54(3):254-264.   Published online February 27, 2016
DOI: https://doi.org/10.1007/s12275-016-5620-z
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AbstractAbstract
Oxylipins are a class of molecules derived from the incorporation of oxygen into polyunsaturated fatty acid substrates through the action of oxygenases. While extensively investigated in the context of mammalian immune responses, over the last decade it has become apparent that oxylipins are a common means of communication among and between plants, animals, and fungi to control development and alter hostmicrobe interactions. In fungi, some oxylipins are derived nonenzymatically while others are produced by lipoxygenases, cyclooxygenases, and monooxygenases with homology to plant and human enzymes. Recent investigations of numerous plant and human fungal pathogens have revealed oxylipins to be involved in the establishment and progression of disease. This review highlights oxylipin production by pathogenic fungi and their role in fungal development and pathogen/ host interactions.

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Research Support, U.S. Gov't, Non-P.H.S.
Synergistic growth in bacteria depends on substrate complexity
Yi-Jie Deng , Shiao Y. Wang
J. Microbiol. 2016;54(1):23-30.   Published online January 5, 2016
DOI: https://doi.org/10.1007/s12275-016-5461-9
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AbstractAbstract
bacterial synergism, lignocellulose degradation, bacterial activity, enzyme production, microbial interaction

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