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      Unveiling the hidden players: exploring the role of gut mycobiome in cancer development and treatment dynamics

      review-article
      , ,
      Gut Microbes
      Taylor & Francis
      Gut mycobiome, cancer development, cancer treatment, Candida, Malassezia, Aspergillus

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          ABSTRACT

          The role of gut fungal species in tumor-related processes remains largely unexplored, with most studies still focusing on fungal infections. This review examines the accumulating evidence suggesting the involvement of commensal and pathogenic fungi in cancer biological process, including oncogenesis, progression, and treatment response. Mechanisms explored include fungal influence on host immunity, secretion of bioactive toxins/metabolites, interaction with bacterial commensals, and migration to other tissues in certain types of cancers. Attempts to utilize fungal molecular signatures for cancer diagnosis and fungal-derived products for treatment are discussed. A few studies highlight fungi’s impact on the responsiveness and sensitivity to chemotherapy, radiotherapy, immunotherapy, and fecal microbiota transplant. Given the limited understanding and techniques in fungal research, the studies on gut fungi are still facing great challenges, despite having great potentials.

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          Most cited references188

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          Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

          Immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizeable minority of cancer patients. Here, we show that primary resistance to ICI can be due to abnormal gut microbiome composition. Antibiotics (ATB) inhibited the clinical benefit of ICI in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICI (but not from non-responding patients) into germ-free or ATB-treated mice ameliorated the antitumor effects of PD-1 blockade. Metagenomics of patient stools at diagnosis revealed correlations between clinical responses to ICI and the relative abundance of Akkermansia muciniphila. Oral supplementation with A. muciniphila post-FMT with non-responder feces restored the efficacy of PD-1 blockade in an IL-12-dependent manner, by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into tumor beds.
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            The NLRP3 inflammasome: molecular activation and regulation to therapeutics

            NLRP3 (NACHT, LRR and PYD domains-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase-1-dependent release of the proinflammatory cytokines, IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical basis of NLRP3 activation and regulation, and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
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              The impact of the gut microbiota on human health: an integrative view.

              The human gut harbors diverse microbes that play a fundamental role in the well-being of their host. The constituents of the microbiota--bacteria, viruses, and eukaryotes--have been shown to interact with one another and with the host immune system in ways that influence the development of disease. We review these interactions and suggest that a holistic approach to studying the microbiota that goes beyond characterization of community composition and encompasses dynamic interactions between all components of the microbiota and host tissue over time will be crucial for building predictive models for diagnosis and treatment of diseases linked to imbalances in our microbiota. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Gut Microbes
                Gut Microbes
                Gut Microbes
                Taylor & Francis
                1949-0976
                1949-0984
                14 March 2024
                2024
                14 March 2024
                : 16
                : 1
                : 2328868
                Affiliations
                [0001]State Key Laboratory of Systems Medicine for Cancer, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute; , Shanghai, China
                Author notes
                CONTACT Haoyan Chen haoyanchen@ 123456sjtu.edu.cn State Key Laboratory of Systems Medicine for Cancer, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute; , Shanghai 200001, China
                [*]

                The authors contributed equally.

                Author information
                https://orcid.org/0000-0001-6722-8534
                Article
                2328868
                10.1080/19490976.2024.2328868
                10950292
                38485702
                b4621ba5-553b-4521-920e-e418a2a4c521
                © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

                History
                Page count
                Figures: 2, References: 188, Pages: 1
                Categories
                Review Article
                Review

                Microbiology & Virology
                gut mycobiome,cancer development,cancer treatment,candida,malassezia,aspergillus

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