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Metformin Regulates Gut Microbiota Abundance to Suppress M2 Skewing of Macrophages and Colorectal Tumorigenesis in Mice
Linfeng Fan , Xiangfu Zeng , Guofeng Xu
J. Microbiol. 2023;61(1):109-120.   Published online January 26, 2023
DOI: https://doi.org/10.1007/s12275-022-00010-8
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AbstractAbstract
The correlation of imbalanced gut microbiota with the onset and progression of colorectal cancer (CRC) has become clear. This work investigates the effect of metformin on gut microbiota and genesis of CRC in mice. Human fecal samples were collected from healthy control (HC) donors and CRC patients. Compared to HC donors, CRC patients had reduced abundance of gut microbiota; however, they had increased abundance of detrimental Bacteroidetes. Mice were injected with azomethane (AOM) to induce colorectal tumorigenesis models. Treatment of CRC patients-sourced fecal microbiota promoted tumorigenesis, and it increased the expression of Ki67, β-catenin, COX-2, and Cyclin D1 in mouse colon tissues. Further treatment of metformin blocked the colorectal tumorigenesis in mice. Fecal microbiota from the metformin-treated mice was collected, which showed decreased Bacteroidetes abundance and suppressed AOM-induced colorectal tumorigenesis in mice as well. Moreover, the metformin- modified microbiota promoted the M1 macrophage-related markers IL-6 and iNOS but suppressed the M2 macrophage-related markers IL-4R and Arg1 in mouse colon tissues. In conclusion, this study suggests that metformin-mediated gut microbiota alteration suppresses macrophage M2 polarization to block colorectal tumorigenesis.

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  • Metformin alleviates colitis-associated colorectal cancer via inhibition of the TLR4/MyD88/NFκB/MAPK pathway and macrophage M2 polarization
    Xueying Lai, Bin Liu, Yu Wan, Ping Zhou, Wanjun Li, Wei Hu, Wei Gong
    International Immunopharmacology.2025; 144: 113683.     CrossRef
  • Metformin as an immunomodulatory agent in enhancing head and neck squamous cell carcinoma therapies
    Wenting Li, Nanshu Liu, Mingwei Chen, Dongjuan Liu, Sai Liu
    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2025; 1880(2): 189262.     CrossRef
  • Clinical efficacy of metformin in familial adenomatous polyposis and the effect of intestinal flora
    Linxin Zhou, Linfu Zheng, Binbin Xu, Zhou Ye, Dazhou Li, Wen Wang
    Orphanet Journal of Rare Diseases.2024;[Epub]     CrossRef
  • An AMPK agonist suppresses the progress of colorectal cancer by regulating the polarization of TAM to M1 through inhibition of HIF-1α and mTOR signal pathway
    Yuanyuan Cao, Mingyi Wo, Chan Xu, Xianming Fei, Juan Jin, Zhiming Shan
    Journal of Cancer Research and Therapeutics.2023; 19(6): 1560.     CrossRef
Mycobiota of ground red pepper and their aflatoxigenic potential
Hyeonheui Ham , Sosoo Kim , Min-Hee Kim , Soohyung Lee , Sung Kee Hong , Jae-Gee Ryu , Theresa Lee
J. Microbiol. 2016;54(12):832-837.   Published online November 26, 2016
DOI: https://doi.org/10.1007/s12275-016-6480-2
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AbstractAbstract
To investigate contamination of ground red pepper with fungi and mycotoxin, we obtained 30 ground red pepper samples from 15 manufacturers in the main chili-pepper-producing areas in Korea. Fungal contamination was evaluated by spreading diluted samples on potato dextrose agar plates. The total fungi counts ranged from 0 to 7.3 × 103 CFU/g. In the samples, the genus Aspergillus had the highest incidence, while Paecilomyces was isolated most frequently. The next most frequent genera were Rhizopus, Penicillium, Cladosporium, and Alternaria. Within Aspergillus, A. ruber was predominant, followed by A. niger, A. amstelodami, A. ochraceus, A. terreus, A. versicolor, A. flavus, and A. fumigatus. The samples were analyzed for aflatoxins, ochratoxin A, and citrinin by ultraperfomance liquid chromatography (UPLC) with a fluorescence detector. Ochratoxin A was detected from three samples at 1.03‒2.08 μg/kg, whereas no aflatoxins or citrinin were detected. To test the potential of fungal isolates to produce aflatoxin, we performed a PCR assay that screened for the norB-cypA gene for 64 Aspergillus isolates. As a result, a single 800-bp band was amplified from 10 A. flavus isolates, and one Aspergillus sp. isolate. UPLC analyses confirmed aflatoxin production by nine A. flavus isolates and one Aspergillus sp. isolate, which produced total aflatoxins at 146.88‒909.53 μg/kg. This indicates that continuous monitoring of ground red pepper for toxigenic fungi is necessary to minimize mycotoxin contamination.

Citations

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  • Screening of mycoflora and ochratoxin A on common culinary herbs and spices in Kenya
    Cynthia Wakhungu, Sheila Okoth, Nicholas Amimo, Peter Wachira, Truphosa Amakhobe, Ann Owiti, Patrick Wachira
    Food Additives & Contaminants: Part A.2024; 41(8): 1003.     CrossRef
  • Aflatoxins in dried chilli products in Gansu Province and health risk
    Yongjun Li, Haiying Yu, Deng Liu, Shan Luo, Xiangna Gao, Lin Zhang, Jianyun Sun
    Food Additives & Contaminants: Part B.2024; 17(4): 352.     CrossRef
  • Kurutmalık Biber Meyvelerinde İç Çürüklüğüne Neden Olan Bazı Fungal Etmenlere Karşı Bitki Uçucu Yağlarının in vitro Antifungal Etkileri
    Mehmet ATAY, Soner SOYLU
    Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi.2023; 26(1): 76.     CrossRef
  • Simultaneous Detection of Ochratoxin A and Aflatoxins in Industrial and Traditional Red andisotPepper Flakes along with Dietary Exposure Risk Assessment
    Sebahat Oztekin, Funda Karbancioglu-Guler
    ACS Omega.2022; 7(36): 31756.     CrossRef
  • Occurrence of Aflatoxins and Ochratoxin A during Merkén Pepper Powder Production in Chile
    Jéssica Costa, Carla Santos, Célia Soares, Rodrigo Rodríguez, Nelson Lima, Cledir Santos
    Foods.2022; 11(23): 3843.     CrossRef
  • Biotreatment, Microbial Community Structure and Valorization Potential of Pepper Processing Wastewater in an Immobilized Cell Bioreactor
    Ioanna Zerva, Nikolaos Remmas, Paraschos Melidis, Georgios Sylaios, Panagiota Stathopoulou, George Tsiamis, Spyridon Ntougias
    Waste and Biomass Valorization.2022; 13(3): 1431.     CrossRef
  • Pulsed light treatment reduces microorganisms and mycotoxins naturally present in red pepper (Capsicum annuum L.) powder
    Henock Woldemichael Woldemariam, Hanna Harmeling, Shimelis Admassu Emire, Paulos Getachew Teshome, Stefan Toepfl, Kemal Aganovic
    Journal of Food Process Engineering.2022;[Epub]     CrossRef
  • Biber meyvelerinde hasat sonrası çürümelere sebep olan bazı fungal hastalık etmenlerine karşı Isothiocyanate bileşiklerinin antifungal etkilerinin belirlenmesi
    Mehmet ATAY, Soner SOYLU
    Harran Tarım ve Gıda Bilimleri Dergisi.2022; 26(3): 290.     CrossRef
  • Paecilomyces formosus MD12, a Biocontrol Agent to Treat Meloidogyne incognita on Brinjal in Green House
    Alaa Baazeem, Mohammed Alorabi, Palanisamy Manikandan, Saqer S. Alotaibi, Abdulaziz Almanea, Ahmed Abdel-Hadi, Ponnuswamy Vijayaraghavan, Subhanandharaj Russalamma Flanet Raj, Young Ock Kim, Hak-Jae Kim
    Journal of Fungi.2021; 7(8): 632.     CrossRef
  • Physicochemical, functional, oxidative stability and rheological properties of red pepper (Capsicum annuum L.) powder and paste
    Henock Woldemichael Woldemariam, Shimelis Admassu Emire, Paulos Getachew Teshome, Stefan Toepfl, Kemal Aganovic
    International Journal of Food Properties.2021; 24(1): 1416.     CrossRef
  • Effects of Temperature and Humidity on Fungal Occurrence in Dried Red Pepper during Storage
    Sosoo Kim, Seul Gi Baek, Nguyen Bao Hung, Se-Ri Kim, Ja Yeong Jang, Jeomsoon Kim, Theresa Lee
    Research in Plant Disease.2021; 27(4): 155.     CrossRef
  • Mycobiota in Chilean chilli Capsicum annuum L. used for production of Merkén
    Jéssica Costa, Rodrigo Rodríguez, Carla Santos, Célia Soares, Nelson Lima, Cledir Santos
    International Journal of Food Microbiology.2020; 334: 108833.     CrossRef
  • Assessment of Microbiological Quality and Mycotoxin in Dried Chili by Morphological Identification, Molecular Detection, and Chromatography Analysis
    Rachma Wikandari, Inggrid Chrisanti Mayningsih, Maura Dania Permata Sari, Fiametta Ayu Purwandari, Widiastuti Setyaningsih, Endang Sutriswati Rahayu, Mohammad J. Taherzadeh
    International Journal of Environmental Research and Public Health.2020; 17(6): 1847.     CrossRef
  • Risk assessment of ochratoxin A in food
    Dieter Schrenk, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina Grasl‐Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean‐Charles Leblanc, Carlo Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Sc
    EFSA Journal.2020;[Epub]     CrossRef
  • A Review on Mycotoxins and Microfungi in Spices in the Light of the Last Five Years
    Darina Pickova, Vladimir Ostry, Jan Malir, Jakub Toman, Frantisek Malir
    Toxins.2020; 12(12): 789.     CrossRef
  • A time travel story: metagenomic analyses decipher the unknown geographical shift and the storage history of possibly smuggled antique marble statues
    Guadalupe Piñar, Caroline Poyntner, Hakim Tafer, Katja Sterflinger
    Annals of Microbiology.2019; 69(10): 1001.     CrossRef
  • Overview of Fungi and Mycotoxin Contamination in Capsicum Pepper and in Its Derivatives
    Jéssica Costa, Rodrigo Rodríguez, Esther Garcia-Cela, Angel Medina, Naresh Magan, Nelson Lima, Paola Battilani, Cledir Santos
    Toxins.2019; 11(1): 27.     CrossRef
  • Fungal food spoilage of supermarkets' displayed fruits
    Iman Saleh, Roda Al-Thani
    Veterinary World.2019; 12(11): 1877.     CrossRef
  • Co-occurrence of toxigenic moulds, aflatoxins, ochratoxin A, Fusarium and Alternaria mycotoxins in fresh sweet peppers (Capsicum annuum) and their processed products.
    L. Gambacorta, D. Magistà, G. Perrone, S. Murgolo, A.F. Logrieco, M. Solfrizzo
    World Mycotoxin Journal.2018; 11(1): 159.     CrossRef
  • Human Pathogenic Paecilomyces from Food
    Danielly C. Moreira, Manoel M. E. Oliveira, Cintia M. Borba
    Microorganisms.2018; 6(3): 64.     CrossRef
Research Support, Non-U.S. Gov't
Biological Control and Plant Growth Promoting Capacity of Rhizobacteria on Pepper under Greenhouse and Field Conditions
Mi-Seon Hahm , Marilyn Sumayo , Ye-Ji Hwang , Seon-Ae Jeon , Sung-Jin Park , Jai Youl Lee , Joon-Hyung Ahn , Byung-Soo Kim , Choong-Min Ryu , Sa-Youl Ghim
J. Microbiol. 2012;50(3):380-385.   Published online June 30, 2012
DOI: https://doi.org/10.1007/s12275-012-1477-y
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AbstractAbstract
Plant growth promoting rhizobacteria Ochrobactrum lupini KUDC1013 and Novosphingobium pentaromativorans KUDC1065 isolated from Dokdo Island, S. Korea are capable of eliciting induced systemic resistance (ISR) in pepper against bacterial spot disease. The present study aimed to determine whether plant growth-promoting rhizobacteria (PGPR) strains including strain KUDC1013, strain KUDC1065, and Paenibacillus polymyxa E681 either singly or in combinations were evaluated to have the capacity for potential biological control and plant growth promotion effect in the field trials. Under greenhouse conditions, the induced systemic resistance (ISR) effect of treatment with strains KUDC1013 and KUDC1065 differed according to pepper growth stages. Drenching of 3-week-old pepper seedlings with the KUDC-1013 strain significantly reduced the disease symptoms. In contrast, treatment with the KUDC1065 strain significantly protected 5-week-old pepper seedlings. Under field conditions, peppers treated with PGPR mixtures containing E681 and KUDC1013, either in a two-way combination, were showed greater effect on plant growth than those treated with an individual treatment. Collectively, the application of mixtures of PGPR strains on pepper might be considered as a potential biological control under greenhouse and field conditions.

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