<i>Fusobacterium nucleatum</i> drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression

Brennan, Caitlin A.; Clay, Slater L.; Lavoie, Sydney; Bae, Sena; Lang, Jessica; Fonseca-Pereira, Diogo; Rosinski, Kathryn G.; Ou, Nora; Glickman, Jonathan N.; Garrett, Wendy S.

doi:10.1080/19490976.2021.1987780

Cited by 73 publications

(46 citation statements)

References 61 publications

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“…While less is known about the type Va SS adhesin Aim1, it was studied because of its homology to Fap2, and similar ability to induce apoptosis in Jurkat cells (86). This and another early study showing Fn's immunosuppressive and proapoptotic effects on lymphocytes and myeloid cells (87) foreshadow later work on Fn's myeloid cell immunomodulatory roles in the Apc Min/+ model ( 88), Fap2's proinflammatory effects on myeloid cells cocultured with colon cancer cells (89), Fap2's interactions with TIGIT (81), and Fn's Th17-enhancing functions in the colon (90). Beyond these four adhesins, ten additional type Va SS autotransporters are encoded by Fn ATCC 23726 (91,92).…”

Section: Enterotoxigenic Bacteroides Fragilismentioning

confidence: 91%

“…Additionally, invasion leads to changes in Fn metabolism. Alterations in Fn amino acid metabolism can increase Fn short-chain fatty acid production that contributes to an IL-17-mediated proinflammatory, tumor-permissive milieu (90). Thus, considering Fn transcriptomes during invasion or within dysplastic and neoplastic sites may provide more targets for CRC prevention and treatment.…”

Section: Fusobacterium Nucleatummentioning

confidence: 99%

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Colorectal cancer: the facts in the case of the microbiota

Clay¹,

Fonseca-Pereira²,

Garrett³

2022

Journal of Clinical Investigation

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Section: Enterotoxigenic Bacteroides Fragilismentioning

confidence: 91%

Section: Fusobacterium Nucleatummentioning

confidence: 99%

Colorectal cancer: the facts in the case of the microbiota

Clay¹,

Fonseca-Pereira²,

Garrett³

2022

Journal of Clinical Investigation

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“…Additionally, bacteria secreted SCFAs demonstrated modulation of immune responses. Fusobacterium nucleatum could drive a pro-inflammatory intestinal microenviroment through the SCFA receptor FFAR2, which drives a dependent modulation of IL-17 expression [ 157 ]. SCFAs have also been shown to enhance the cytotoxic activity and the memory potential of CD8 T cells.…”

Section: Lipid Metabolism In the Tumor Microenvironmentmentioning

confidence: 99%

Lipid Metabolism Interplay in CRC—An Update

2022

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Colorectal cancer (CRC) to date still ranks as one of the deadliest cancer entities globally, and despite recent advances, the incidence in young adolescents is dramatically increasing. Lipid metabolism has recently received increased attention as a crucial element for multiple aspects of carcinogenesis and our knowledge of the underlying mechanisms is steadily growing. However, the mechanism how fatty acid metabolism contributes to CRC is still not understood in detail. In this review, we aim to summarize our vastly growing comprehension and the accompanied complexity of cellular fatty acid metabolism in CRC by describing inputs and outputs of intracellular free fatty acid pools and how these contribute to cancer initiation, disease progression and metastasis. We highlight how different lipid pathways can contribute to the aggressiveness of tumors and affect the prognosis of patients. Furthermore, we focus on the role of lipid metabolism in cell communication and interplay within the tumor microenvironment (TME) and beyond. Understanding these interactions in depth might lead to the discovery of novel markers and new therapeutic interventions for CRC. Finally, we discuss the crucial role of fatty acid metabolism as new targetable gatekeeper in colorectal cancer.

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“…Moreover, Brennan et al. suggested that F. nucleatum influenced intestinal immunity by shaping Th17 responses in an FFAR2-dependent manner ( 78 ). Although further studies are necessary to clarify the multifaceted roles of FFAR2, this research highlighted a conserved pathway that could be targeted to attenuate oncomicrobe-mediated CRC.…”

Section: Gut Microbiota and Gastrointestinal Cancermentioning

confidence: 99%

The Emerging Roles of Human Gut Microbiota in Gastrointestinal Cancer

Guo

Qin

et al. 2022

Front. Immunol.

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The gut microbiota is composed of a large number of microorganisms with a complex structure. It participates in the decomposition, digestion, and absorption of nutrients; promotes the development of the immune system; inhibits the colonization of pathogens; and thus modulates human health. In particular, the relationship between gut microbiota and gastrointestinal tumor progression has attracted widespread concern. It was found that the gut microbiota can influence gastrointestinal tumor progression in independent ways. Here, we focused on the distribution of gut microbiota in gastrointestinal tumors and further elaborated on the impact of gut microbiota metabolites, especially short-chain fatty acids, on colorectal cancer progression. Additionally, the effects of gut microbiota on gastrointestinal tumor therapy are outlined. Finally, we put forward the possible problems in gut microbiota and the gastrointestinal oncology field and the efforts we need to make.

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Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression

Cited by 73 publications

References 61 publications

Colorectal cancer: the facts in the case of the microbiota

Colorectal cancer: the facts in the case of the microbiota

Lipid Metabolism Interplay in CRC—An Update

The Emerging Roles of Human Gut Microbiota in Gastrointestinal Cancer

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