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Journal ArticleDOI

Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality.

Shuang Wang1, Yang Liu1, Jun Li1, Lei Zhao1, Wei Yan1, Baiqiang Lin1, Xiao Guo1, Yunwei Wei1 
20 Aug 2021-Frontiers in Cell and Developmental Biology (Frontiers Media SA)-Vol. 9, pp 710165-710165
TL;DR: In this paper, the authors summarized the biological characteristics of Fusobacterium nucleatum and the epidemiological associations between F. nucleatum, and highlighted the mechanisms by which F.ucleatum participates in CRC progression, metastasis, and chemoresistance by affecting cancer cells or regulating the tumor microenvironment.
Abstract: Colorectal cancer (CRC) is a common cancer worldwide with complex etiology. Fusobacterium nucleatum (F. nucleatum), an oral symbiotic bacterium, has been linked with CRC in the past decade. A series of gut microbiota studies show that CRC patients carry a high abundance of F. nucleatum in the tumor tissue and fecal, and etiological studies have clarified the role of F. nucleatum as a pro-carcinogenic bacterium in various stages of CRC. In this review, we summarize the biological characteristics of F. nucleatum and the epidemiological associations between F. nucleatum and CRC, and then highlight the mechanisms by which F. nucleatum participates in CRC progression, metastasis, and chemoresistance by affecting cancer cells or regulating the tumor microenvironment (TME). We also discuss the research gap in this field and give our perspective for future studies. These findings will pave the way for manipulating gut F. nucleatum to deal with CRC in the future.

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Citations
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Journal ArticleDOI
TL;DR: In this article , the authors discussed emerging and exciting evidence of complex and important connections between the oral microbes and multiple human systemic diseases, and the possible contribution of the oral microorganisms to systemic diseases.
Abstract: Oral bacteria directly affect the disease status of dental caries and periodontal diseases. The dynamic oral microbiota cooperates with the host to reflect the information and status of immunity and metabolism through two-way communication along the oral cavity and the systemic organs. The oral cavity is one of the most important interaction windows between the human body and the environment. The microenvironment at different sites in the oral cavity has different microbial compositions and is regulated by complex signaling, hosts, and external environmental factors. These processes may affect or reflect human health because certain health states seem to be related to the composition of oral bacteria, and the destruction of the microbial community is related to systemic diseases. In this review, we discussed emerging and exciting evidence of complex and important connections between the oral microbes and multiple human systemic diseases, and the possible contribution of the oral microorganisms to systemic diseases. This review aims to enhance the interest to oral microbes on the whole human body, and also improve clinician's understanding of the role of oral microbes in systemic diseases. Microbial research in dentistry potentially enhances our knowledge of the pathogenic mechanisms of oral diseases, and at the same time, continuous advances in this frontier field may lead to a tangible impact on human health.

62 citations

Journal ArticleDOI
11 Aug 2022-Gut
TL;DR: The predictive model based on metagenomic, metabolomic and KO gene markers achieved a powerful classification performance for distinguishing EO-CRC from controls, suggesting that altered microbiome–metabolome interplay helps explain the pathogenesis of EO.CRC.
Abstract: Objective The incidence of early-onset colorectal cancer (EO-CRC) is steadily increasing. Here, we aimed to characterise the interactions between gut microbiome, metabolites and microbial enzymes in EO-CRC patients and evaluate their potential as non-invasive biomarkers for EO-CRC. Design We performed metagenomic and metabolomic analyses, identified multiomics markers and constructed CRC classifiers for the discovery cohort with 130 late-onset CRC (LO-CRC), 114 EO-CRC subjects and age-matched healthy controls (97 LO-Control and 100 EO-Control). An independent cohort of 38 LO-CRC, 24 EO-CRC, 22 LO-Controls and 24 EO-Controls was analysed to validate the results. Results Compared with controls, reduced alpha-diversity was apparent in both, LO-CRC and EO-CRC subjects. Although common variations existed, integrative analyses identified distinct microbiome–metabolome associations in LO-CRC and EO-CRC. Fusobacterium nucleatum enrichment and short-chain fatty acid depletion, including reduced microbial GABA biosynthesis and a shift in acetate/acetaldehyde metabolism towards acetyl-CoA production characterises LO-CRC. In comparison, multiomics signatures of EO-CRC tended to be associated with enriched Flavonifractor plauti and increased tryptophan, bile acid and choline metabolism. Notably, elevated red meat intake-related species, choline metabolites and KEGG orthology (KO) pldB and cbh gene axis may be potential tumour stimulators in EO-CRC. The predictive model based on metagenomic, metabolomic and KO gene markers achieved a powerful classification performance for distinguishing EO-CRC from controls. Conclusion Our large-sample multiomics data suggest that altered microbiome–metabolome interplay helps explain the pathogenesis of EO-CRC and LO-CRC. The potential of microbiome-derived biomarkers as promising non-invasive tools could be used for the accurate detection and distinction of individuals with EO-CRC.

23 citations

Journal ArticleDOI
TL;DR: Gut microbiota and their metabolites influence the progression and causation of CRC, and the association analysis of metabolomics and gut microbiome will provide novel strategies for the prevention, diagnosis, and therapy of CRC.
Abstract: Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. The etiology and pathogenesis of CRC remain unclear. A growing body of evidence suggests dysbiosis of gut bacteria can contribute to the occurrence and development of CRC by generating harmful metabolites and changing host physiological processes. Metabolomics, a systems biology method, will systematically study the changes in metabolites in the physiological processes of the body, eventually playing a significant role in the detection of metabolic biomarkers and improving disease diagnosis and treatment. Metabolomics, in particular, has been highly beneficial in tracking microbially derived metabolites, which has substantially advanced our comprehension of host-microbiota metabolic interactions in CRC. This paper has briefly compiled recent research progress of the alterations of intestinal flora and its metabolites associated with CRC and the application of association analysis of metabolomics and gut microbiome in the diagnosis, prevention, and treatment of CRC; furthermore, we discuss the prospects for the problems and development direction of this association analysis in the study of CRC. Gut microbiota and their metabolites influence the progression and causation of CRC, and the association analysis of metabolomics and gut microbiome will provide novel strategies for the prevention, diagnosis, and therapy of CRC.

22 citations

Journal ArticleDOI
TL;DR: In this article , the authors examined associations between dysbiosis in the skin and gut microbiome and the melanoma growth using MeLiM porcine model of melanoma progression and spontaneous regression.
Abstract: The microbiome alterations are associated with cancer growth and may influence the immune system and response to therapy. Particularly, the gut microbiome has been recently shown to modulate response to melanoma immunotherapy. However, the role of the skin microbiome has not been well explored in the skin tumour microenvironment and the link between the gut microbiome and skin microbiome has not been investigated in melanoma progression. Therefore, the aim of the present study was to examine associations between dysbiosis in the skin and gut microbiome and the melanoma growth using MeLiM porcine model of melanoma progression and spontaneous regression.Parallel analysis of cutaneous microbiota and faecal microbiota of the same individuals was performed in 8 to 12 weeks old MeLiM piglets. The bacterial composition of samples was analysed by high throughput sequencing of the V4-V5 region of the 16S rRNA gene. A significant difference in microbiome diversity and richness between melanoma tissue and healthy skin and between the faecal microbiome of MeLiM piglets and control piglets were observed. Both Principal Coordinate Analysis and Non-metric multidimensional scaling revealed dissimilarities between different bacterial communities. Linear discriminant analysis effect size at the genus level determined different potential biomarkers in multiple bacterial communities. Lactobacillus, Clostridium sensu stricto 1 and Corynebacterium 1 were the most discriminately higher genera in the healthy skin microbiome, while Fusobacterium, Trueperella, Staphylococcus, Streptococcus and Bacteroides were discriminately abundant in melanoma tissue microbiome. Bacteroides, Fusobacterium and Escherichia-Shigella were associated with the faecal microbiota of MeLiM piglets. Potential functional pathways analysis based on the KEGG database indicated significant differences in the predicted profile metabolisms between the healthy skin microbiome and melanoma tissue microbiome. The faecal microbiome of MeLiM piglets was enriched by genes related to membrane transports pathways allowing for the increase of intestinal permeability and alteration of the intestinal mucosal barrier.The associations between melanoma progression and dysbiosis in the skin microbiome as well as dysbiosis in the gut microbiome were identified. Results provide promising information for further studies on the local skin and gut microbiome involvement in melanoma progression and may support the development of new therapeutic approaches.

12 citations

Journal ArticleDOI
TL;DR: In this article , the authors examined associations between dysbiosis in the skin and gut microbiome and the melanoma growth using MeLiM porcine model of melanoma progression and spontaneous regression.
Abstract: The microbiome alterations are associated with cancer growth and may influence the immune system and response to therapy. Particularly, the gut microbiome has been recently shown to modulate response to melanoma immunotherapy. However, the role of the skin microbiome has not been well explored in the skin tumour microenvironment and the link between the gut microbiome and skin microbiome has not been investigated in melanoma progression. Therefore, the aim of the present study was to examine associations between dysbiosis in the skin and gut microbiome and the melanoma growth using MeLiM porcine model of melanoma progression and spontaneous regression.Parallel analysis of cutaneous microbiota and faecal microbiota of the same individuals was performed in 8 to 12 weeks old MeLiM piglets. The bacterial composition of samples was analysed by high throughput sequencing of the V4-V5 region of the 16S rRNA gene. A significant difference in microbiome diversity and richness between melanoma tissue and healthy skin and between the faecal microbiome of MeLiM piglets and control piglets were observed. Both Principal Coordinate Analysis and Non-metric multidimensional scaling revealed dissimilarities between different bacterial communities. Linear discriminant analysis effect size at the genus level determined different potential biomarkers in multiple bacterial communities. Lactobacillus, Clostridium sensu stricto 1 and Corynebacterium 1 were the most discriminately higher genera in the healthy skin microbiome, while Fusobacterium, Trueperella, Staphylococcus, Streptococcus and Bacteroides were discriminately abundant in melanoma tissue microbiome. Bacteroides, Fusobacterium and Escherichia-Shigella were associated with the faecal microbiota of MeLiM piglets. Potential functional pathways analysis based on the KEGG database indicated significant differences in the predicted profile metabolisms between the healthy skin microbiome and melanoma tissue microbiome. The faecal microbiome of MeLiM piglets was enriched by genes related to membrane transports pathways allowing for the increase of intestinal permeability and alteration of the intestinal mucosal barrier.The associations between melanoma progression and dysbiosis in the skin microbiome as well as dysbiosis in the gut microbiome were identified. Results provide promising information for further studies on the local skin and gut microbiome involvement in melanoma progression and may support the development of new therapeutic approaches.

12 citations

References
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Journal ArticleDOI
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Journal ArticleDOI
TL;DR: Progress against CRC can be accelerated by increasing access to guideline‐recommended screening and high‐quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle‐aged adults.
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2,928 citations

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TL;DR: By parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
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2,920 citations

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TL;DR: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.
Abstract: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.

2,083 citations

Journal ArticleDOI
TL;DR: Data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression, and this work finds that F.nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis.

1,704 citations