Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacterium in the mesenchymal subtype

Younginger, Brett S.; Mayba, Oleg; Reeder, Jens; Nagarkar, Deepti R.; Modrušan, Zora; Albert, Matthew L.; Byrd, Allyson L.

doi:10.1016/j.xcrm.2023.100920

Cited by 22 publications

(22 citation statements)

References 102 publications

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“…This post‐appendectomy “immune switch” further comprises of molecular changes such as a reduction in PD1 expression in CD4+ and CD8+ T cells post‐appendectomy and a decreased ratio of T effector memory to T central memory cells. We further postulate that the molecular profile of CRC, namely, that of MSI‐H/dMMR CRC, might also be affected by appendectomy given that the proximal pattern of presentation of CRC post‐appendectomy appears to correlate with the right‐sided preponderance of MSI‐H/dMMR CRC, alongside recent reports that the microbiome in MSI‐H/dMMR CRC is altered with increased species of Bacteroides, Prevotella , and Fusobacterium , which are species identified to be both CRC‐inducing and upregulated in the post‐appendectomy gut microbiome 8,21,53 …”

Section: Present Role Of the Appendix: Vestigial Organ Or Important R...mentioning

confidence: 56%

“…We further postulate that the molecular profile of CRC, namely, that of MSI-H/dMMR CRC, might also be affected by appendectomy given that the proximal pattern of presentation of CRC post-appendectomy appears to correlate with the right-sided preponderance of MSI-H/dMMR CRC, alongside recent reports that the microbiome in MSI-H/dMMR CRC is altered with increased species of Bacteroides, Prevotella, and Fusobacterium, which are species identified to be both CRC-inducing and upregulated in the post-appendectomy gut microbiome. 8,21,53 We thus hypothesize that the immunology of the colon, particularly that of the proximal colon, is altered post-appendectomy, favoring tumorigenesis in part due to reduced immune regulation and surveillance. We propose that further studies conducted should not solely aim to investigate the location of tumors post-appendectomy and advocate taking further steps in characterizing tumors through an identification of molecular and transcriptomic profiles (MSI-H/dMMR, BRAF), cell-surface proteins, and immune signaling (PD1, PD-L1, IL-17A).…”

Section: Specific Pathways Of Microbiome Dysregulation Post-appendectomymentioning

confidence: 99%

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Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer

Yap,

Lui,

Samol

et al. 2024

J of Gastro and Hepatol

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The role of appendectomy in the pathogenesis of colorectal cancer (CRC) is a recent topic of contention. Given that appendectomy remains one of the most commonly performed operations and a first‐line management strategy of acute appendicitis, it is inherently crucial to elucidate the association between prior appendectomy and subsequent development of CRC, as there may be long‐term health repercussions. In this review, we summarize the data behind the relationship of CRC in post‐appendectomy patients, discuss the role of the microbiome in relation to appendectomy and CRC pathogenesis, and provide an appraisal of our current understanding of the function of the appendix. We seek to piece together the current landscape surrounding the microbiome and immunological changes in the colon post‐appendectomy and suggest a direction for future research involving molecular, transcriptomic, and immunologic analysis to complement our current understanding of the alterations in gut microbiome.

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Section: Present Role Of the Appendix: Vestigial Organ Or Important R...mentioning

confidence: 56%

Section: Specific Pathways Of Microbiome Dysregulation Post-appendectomymentioning

confidence: 99%

Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer

Yap,

Lui,

Samol

et al. 2024

J of Gastro and Hepatol

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“…Barrier deterioration induced by CRC‐initiating genetic lesions or inflammation results in the invasion of microbiota, which contributes to tumor development 39 . Oral‐derived microbiome, including four Fusobacterium spp., was found to be enriched in colorectal tumors 40,41 ; although the reason why these bacteria translocated from the oral to gut was not fully illustrated, several studies have revealed the potential way. A previous study revealed that the common oral bacterium Fusobacterium nucleatum was more likely to translocate to CRC using the hematogenous route 42 .…”

Section: The Colonization Of Microbiome In the Tumor Microenvironmentmentioning

confidence: 99%

Intratumor microbiome: selective colonization in the tumor microenvironment and a vital regulator of tumor biology

Jiang,

Yang,

Dai

et al. 2023

MedComm

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The polymorphic microbiome has been proposed as a new hallmark of cancer. Intratumor microbiome has been revealed to play vital roles in regulating tumor initiation and progression, but the regulatory mechanisms have not been fully uncovered. In this review, we illustrated that similar to other components in the tumor microenvironment, the reside and composition of intratumor microbiome are regulated by tumor cells and the surrounding microenvironment. The intratumor hypoxic, immune suppressive, and highly permeable microenvironment may select certain microbiomes, and tumor cells may directly interact with microbiome via molecular binding or secretions. Conversely, the intratumor microbiomes plays vital roles in regulating tumor initiation and progression via regulating the mutational landscape, the function of genes in tumor cells and modulating the tumor microenvironment, including immunity, inflammation, angiogenesis, stem cell niche, etc. Moreover, intratumor microbiome is regulated by anti‐cancer therapies and actively influences therapy response, which could be a therapeutic target or engineered to be a therapy weapon in the clinic. This review highlights the intratumor microbiome as a vital component in the tumor microenvironment, uncovers potential mutual regulatory mechanisms between the tumor microenvironment and intratumor microbiome, and points out the ongoing research directions and drawbacks of the research area, which should broaden our view of microbiome and enlighten further investigation directions.

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“…F. nucleatum has also long been recognized for its prominent role in a variety of oral diseases, especially odontogenic abscesses and periodontitis (3). Similarly, F. nucleatum has garnered widespread attention due to its prominent association with multiple extraoral conditions, including preterm birth, head and neck cancers, colorectal cancer (CRC), and others (4)(5)(6)(7)(8)(9)(10)(11). F. nucleatum has been shown to target specific innate immune signaling pathways and modulate the autophagic response, leading to enhanced chemoresistance in CRC (12).…”

Section: Introductionmentioning

confidence: 99%

“…Given the recent evidence implicating Fn. animalis as the predominant subspecies associated with CRC tumors (4, 10, 19) as well as its likely origination in the oral cavity (17, 20), these questions are particularly timely.…”

Section: Introductionmentioning

confidence: 99%

The prevalence ofFusobacterium nucleatumsubspecies in the oral cavity stratifies by local health status

Krieger,

AbdelRahman,

Choi

et al. 2023

Preprint

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The ubiquitous inflammophilic pathobiont Fusobacterium nucleatum is widely recognized for its strong association with a variety of human dysbiotic diseases such as periodontitis and oral/extraoral abscesses, as well as multiple types of cancer. F. nucleatum is currently subdivided into four subspecies: F. nucleatum subspecies nucleatum (Fn. nucleatum), animalis (Fn. animalis), polymorphum (Fn. polymorphum), and vincentii/fusiforme (Fn. vincentii). Although these subspecies have been historically considered as functionally interchangeable in the oral cavity, direct clinical evidence is largely lacking for this assertion. Consequently, we assembled a collection of oral clinical specimens to determine whether F. nucleatum subspecies prevalence in the oral cavity stratifies by local oral health status. Patient-matched clinical specimens of both disease-free dental plaque and odontogenic abscess were analyzed with newly developed culture-dependent and culture-independent approaches using 44 and 60 oral biofilm/tooth abscess paired specimens, respectively. Most oral cavities were found to simultaneously harbor multiple F. nucleatum subspecies, with a greater diversity present within dental plaque compared to abscesses. In dental plaque, Fn. polymorphum is clearly the dominant organism, but this changes dramatically within odontogenic abscesses where Fn. animalis is heavily favored over all other fusobacteria. Surprisingly, the most commonly studied F. nucleatum subspecies, Fn. nucleatum, is only a minor constituent in the oral cavity. To gain further insights into the genetic basis for these phenotypes, we subsequently performed pangenome, phylogenetic, and functional enrichment analyses of oral fusobacterial genomes using the Anvi'o platform, which revealed significant genotypic distinctions among F. nucleatum subspecies. Accordingly, our results strongly support a taxonomic reassignment of each F. nucleatum subspecies into distinct Fusobacterium species. Of these, Fn. animalis should be considered as the most clinically relevant at sites of active inflammation, despite being among the least characterized oral fusobacteria.

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Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacterium in the mesenchymal subtype

Cited by 22 publications

References 102 publications

Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer

Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer

Intratumor microbiome: selective colonization in the tumor microenvironment and a vital regulator of tumor biology

The prevalence ofFusobacterium nucleatumsubspecies in the oral cavity stratifies by local health status

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