-
Cancer Epidemiology, Biomarkers &... Jan 2022() activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.
BACKGROUND
() activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.
METHODS
We characterized and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of , , and bacterial genes in tumors from 1,994 patients with colorectal cancer and assessed associations between presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations.
RESULTS
, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies . Presence of was associated with higher colorectal cancer-specific mortality (HR, 1.97; = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; = 0.029). Only subspecies , the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; = 0.0016), subspecies and were not (HR, 1.07; = 0.86). Additional adjustment for tumor stage suggests that the effect of on mortality is partly driven by a stage shift. Presence of was associated with microsatellite instable tumors, tumors with exonuclease domain mutations, and mutations, and suggestively associated with mutations.
CONCLUSIONS
, and particularly subspecies , was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.
IMPACT
Our findings identify the subspecies as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance.
Topics: Carcinogenesis; Colorectal Neoplasms; Fusobacterium nucleatum; Humans; RNA, Ribosomal, 16S
PubMed: 34737207
DOI: 10.1158/1055-9965.EPI-21-0463 -
Cancers Nov 2023Oral squamous cell carcinoma (OSCC) is the most common oral cavity malignancy associated with multiple risk factors. In the last 14 years, oral dysbiosis has attracted... (Review)
Review
Oral squamous cell carcinoma (OSCC) is the most common oral cavity malignancy associated with multiple risk factors. In the last 14 years, oral dysbiosis has attracted the scientific community's attention as a potential oncogenic factor, in parallel with the development of omics technologies that have revolutionized microbiological research. The present umbrella review aimed to investigate the oral microbiological content (bacilli, viruses, and fungi) of tissue and saliva samples from adult (>18 years) patients with OSCC. The secondary objective was to compare the oral microbiome of OSCC subjects with non-OSCC subjects. The study protocol was under the PRISMA statement and registered on PROSPERO (CRD42023448153). Data from 32 systematic reviews were extracted, qualitatively summarized, and analyzed using AMSTAR-2. An increase in oral bacteria of the phylum Fusobacteria, Proteobacteria, and Bacteroidetes and a decrease in Firmicutes and Actinobacteria were observed in OSCC patients. The increased bacterial genera were periodontopathogens. The most common viruses were EBV and HPV, especially the high-risk genotypes. Candida was the most studied oral fungus and was always increased in OSCC subjects. Further studies should investigate the possible carcinogenic mechanisms of oral microorganisms found increased in tissue samples and saliva from adult subjects with OSCC.
PubMed: 38067244
DOI: 10.3390/cancers15235540 -
Gut Microbes 2024The anaerobic bacterium is significantly associated with human colorectal cancer (CRC) and is considered a significant contributor to the disease. The mechanisms...
The anaerobic bacterium is significantly associated with human colorectal cancer (CRC) and is considered a significant contributor to the disease. The mechanisms underlying the promotion of intestinal tumor formation by have only been partially uncovered. Here, we showed that releases a metabolite into the microenvironment that strongly activates NF-κB in intestinal epithelial cells via the ALPK1/TIFA/TRAF6 pathway. Furthermore, we showed that the released molecule had the biological characteristics of ADP-heptose. We observed that induction of this pathway increased the expression of the inflammatory cytokine IL-8 and two anti-apoptotic genes known to be implicated in CRC, and . Finally, it promoted the survival of CRC cells and reduced 5-fluorouracil chemosensitivity . Taken together, our results emphasize the importance of the ALPK1/TIFA pathway in induced-CRC pathogenesis, and identify the role of ADP-H in this process.
Topics: Humans; Fusobacterium nucleatum; Base Composition; Gastrointestinal Microbiome; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Colorectal Neoplasms; Heptoses; Tumor Microenvironment
PubMed: 38126163
DOI: 10.1080/19490976.2023.2295384 -
Frontiers in Cellular and Infection... 2023(FN) plays a pivotal role in the development and progression of colorectal cancer by modulating antitumor immune responses. However, the impact of FN on immune...
BACKGROUND & AIMS
(FN) plays a pivotal role in the development and progression of colorectal cancer by modulating antitumor immune responses. However, the impact of FN on immune regulation in the tumor microenvironment has not been fully elucidated.
METHODS
The abundance of FN was measured in 99 stage III CRC tumor tissues using quantitative polymerase chain reaction. Gene expression profiles were assessed and annotated using consensus molecular subtypes (CMS), Gene Ontology (GO) analysis, and deconvolution of individual immune cell types in the context of FN abundance. Immune profiling for tumor infiltrating T cells isolated from human tumor tissues was analyzed using flow cytometry. tumor-infiltrating T cells were stimulated in the presence or absence of FN to determine the direct effects of FN on immune cell phenotypes.
RESULTS
Gene expression profiles, CMS composition, abundance of immune cell subtypes, and survival outcomes differed depending on FN infection. We found that FN infection was associated with poorer disease-free survival and overall survival in stage III CRC patients. FN infection was associated with T cell depletion and enrichment of exhausted CD8 and FoxP3 regulatory T cells in the tumor microenvironment. The presence of FN in tumors was correlated with a suppressive tumor microenvironment in a T cell-dependent manner.
CONCLUSION
FN enhanced the suppressive immune microenvironment with high depletion of CD8 T cells and enrichment of FoxP3 regulatory T cells in human colorectal cancer cases. Our findings suggest a potential association for FN in adaptive immunity, with biological and prognostic implications.
Topics: Humans; Colorectal Neoplasms; Fusobacterium nucleatum; Tumor Microenvironment; CD8-Positive T-Lymphocytes; Adaptive Immunity; Forkhead Transcription Factors
PubMed: 36960042
DOI: 10.3389/fcimb.2023.1101291 -
Frontiers in Cellular and Infection... 2021Gut microbiome alteration was closely associated with colorectal cancer (CRC). Previous studies had demonstrated the bacteria composition changes but lacked virome...
Gut microbiome alteration was closely associated with colorectal cancer (CRC). Previous studies had demonstrated the bacteria composition changes but lacked virome profiles, trans-kindom interactions, and reliable diagnostic model explorations in CRC. Hence, we performed metagenomic sequencing to investigate the gut microbiome and microbial interactions in adenoma and CRC patients. We found the decreased microbial diversity in CRC and revealed the taxonomic alterations of bacteria and viruses were highly associated with CRC at the species level. The relative abundance of oral-derived species, such as , , , and , increased. At the same time, butyrate-producing and anti-inflammatory microbes decreased in adenoma and CRC by non-parametric Kruskal-Wallis test. Despite that, the relative abundance of and increased, whereas some phages, including and , decreased along with CRC development. Gut bacteria was negatively associated with viruses in CRC and healthy control by correlation analysis (P=0.017 and 0.002, respectively). Viruses were much more dynamic than the bacteria as the disease progressed, and the altered microbial interactions were distinctively stage-dependent. The degree centrality of microbial interactions decreased while closeness centrality increased along with the adenoma to cancer development. was the key bacteriophage that enriched in healthy controls and positively associated with butyrate-producing bacteria. Diagnostic tests based on bacteria by random forest confirmed in independent cohorts showed better performance than viruses for CRC. In conclusion, our study revealed the novel CRC-associated bacteria and viruses that exhibited specific differences and intensive microbial correlations, which provided a reliable diagnostic panel for CRC.
Topics: Bacteria; Colorectal Neoplasms; Feces; Fusobacterium; Humans; Viruses
PubMed: 34307189
DOI: 10.3389/fcimb.2021.657867 -
Scientific Reports Mar 2023Helicobacter pylori (H. pylori) infection has been considered as the main causal factor in gastric carcinogenesis, but other bacterial species may also play an important...
Helicobacter pylori (H. pylori) infection has been considered as the main causal factor in gastric carcinogenesis, but other bacterial species may also play an important role in pathophysiology of gastric cancer. The aim of the study was to explore the link between gastric cancer prognosis and the mucosal microbial community in tumorous and adjacent gastric tissue. The bacterial profile was analysed using 16S sequencing (V1-V2 region). Microbial differences were mostly characterized by lower relative abundances of H. pylori in tumorous gastric tissues. Bacterial community and outcome data analysis revealed the genus Fusobacterium and Prevotella significantly associated with worse overall survival in gastric cancer patients. In particular, Fusobacterium was associated with significant increase in hazard ratio in both univariable and multivariable analysis and independently validated using TCMA data. Phylogenetic biodiversity of Fusobacterium species in the stomach revealed F. periodonticum as the most prevalent in healthy subjects, while F. nucleatum was most abundant in patients with gastric cancer. Bacterial community network analysis in gastric cancer suggests substantial complexity and a strong interplay between F. nucleatum and Prevotella. In summary, mucosal microbial community in the stomach was associated with worse overall survival in gastric cancer patients. Strongest negative impact on prognosis was linked to the abundance of F. nucleatum in tumorous specimens, suggesting its translational relevance in management of gastric cancer patients.
Topics: Humans; Stomach Neoplasms; Gastric Mucosa; Phylogeny; Bacteria; Fusobacterium; Prognosis; Helicobacter Infections; Helicobacter pylori; RNA, Ribosomal, 16S
PubMed: 36944721
DOI: 10.1038/s41598-023-31740-3 -
Medicine Mar 2023Acupoint application has served as an important complementary and adjunctive therapy in China. The purpose of this study is to explore the impact of summer acupoint... (Randomized Controlled Trial)
Randomized Controlled Trial
Acupoint application has served as an important complementary and adjunctive therapy in China. The purpose of this study is to explore the impact of summer acupoint application treatment (SAAT) on the abundance and biological structure of gut microbiota in healthy Asian adults. Based on the CONSORT guidelines, 72 healthy adults were included in this study, randomly divided into 2 groups, receiving either traditional (acupoint application within known relevant meridians, Group A) or sham (treated with placebo prepared by mixing the equal amount of starch and water, Group B) SAAT. SAAT stickers include extracts from Rhizoma Corydalis, Sinapis alba, Euphorbia kansui, Asari Herba, and the treatment group received 3 sessions of SAAT for 24 months, administered to BL13 (Feishu), BL17 (Geshu), BL20 (Pishu), and BL23 (Shenshu) acupoints. Fecal microbial analyses via ribosomal ribonucleic acid (rRNA) sequencing were performed on donor stool samples before and after 2 years of SAAT or placebo treatment to analyze the abundances, diversity, and structure of gut microbiota. No significant baseline differences were present between groups. At the phylum level, the baseline relative abundance of Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria was identified in fecal samples collected from each group. After treatment, the relative abundance of Firmicutes was significantly increased in both groups (P < .05). Notably, a significant decrease in the relative abundance of Fusobacteria was observed in the SAAT treatment group (P < .001), while the abundance of Bacteroidetes was decreased significantly in the placebo group (P < .05). At the genus level, the relative abundance of Faecalibacterium and Subdoligranulum species in the 2 groups were all significantly increased (P < .05). In addition, a significant reduction in the relative abundance of Blautia, Bacteroides, and Dorea in Group A (P < .05) and Eubacterium hallii group and Anaerostipes (P < .05) in Group B was observed after treatment. Our findings indicated SAAT substantially influenced the bacterial community structure in the gut microbiota of healthy Asian adults, which might serve as potential therapeutic targets for related diseases, and provided a foundation for future studies aimed at elucidating the microbial mechanisms underlying SAAT for the treatment of various conditions such as obesity, insulin resistance, irritable bowel syndrome.
Topics: Adult; Humans; Acupuncture Points; Asian; Firmicutes; Fusobacteria; Gastrointestinal Microbiome
PubMed: 36862868
DOI: 10.1097/MD.0000000000032951 -
European Review For Medical and... Jul 2021The human being has evolved in close symbiosis with its own ecological community of commensal, symbiotic and pathogenic bacteria. After the intestinal microbiome, that... (Review)
Review
OBJECTIVE
The human being has evolved in close symbiosis with its own ecological community of commensal, symbiotic and pathogenic bacteria. After the intestinal microbiome, that of the oral cavity is the largest and most diversified. Its importance is reflected not only in local and systemic diseases, but also in pregnancy since it would seem to influence the placental microbiome.
MATERIALS AND METHODS
This is a literature review of articles published in PubMed about Fusobacterium Nucleatum and both its implications with systemic and oral health, adverse pregnancy outcomes, flavors perception and its interference in the oral-nasal mucosal immunity.
RESULTS
It is in maintaining the microbiome's homeostasis that the Fusobacterium nucleatum, an opportunistic periodontal pathogen of the oral cavity, plays a crucial role both as a bridge microorganism of the tongue biofilm, and in maintaining the balance between the different species in the oral-nasal mucosal immunity also by taste receptors interaction. It is also involved in the flavor perception and its detection in the oral microbiome of children from the first days of life suggests a possible physiological role. However, the dysbiosis can determine its pathogenicity with local and systemic consequences, including the pathogenesis of respiratory infections.
CONCLUSIONS
It is interesting to evaluate its possible correlation with Sars-CoV-2 and the consequences on the microflora of the oral cavity, both to promote a possible broad-spectrum preventive action, in favor of all subjects for whom, by promoting the eubiosis of the oral microbiome, a defensive action could be envisaged by the commensals themselves but, above all, for patients with specific comorbidities and therefore already prone to oral dysbiosis.
Topics: COVID-19; Female; Fusobacterium nucleatum; Humans; Mouth; Pregnancy
PubMed: 34286500
DOI: 10.26355/eurrev_202107_26251 -
FASEB Journal : Official Publication of... Jan 2024Bacterial infection is the main cause of pulpitis. However, whether a dominant bacteria can promote the progression of pulpitis and its underlying mechanism remains...
Bacterial infection is the main cause of pulpitis. However, whether a dominant bacteria can promote the progression of pulpitis and its underlying mechanism remains unclear. We provided a comprehensive assessment of the microbiota alteration in pulpitis using 16S rRNA sequencing. Fusobacterium nucleatum was the most enriched in pulpitis and played a pathogenic role accelerating pulpitis progression in rat pulpitis model. After odontoblast-like cells cocultured with F. nucleatum, the stimulator of interferon genes (STING) pathway and autophagy were activation. There was a float of STING expression during F. nucleatum stimulation. STING was degraded by autophagy at the early stage. At the late stage, F. nucleatum stimulated mitochondrial Reactive Oxygen Species (ROS) production, mitochondrial dysfunction and then mtDNA escape into cytosol. mtDNA, which escaped into cytosol, caused more cytosolic mtDNA binds to cyclic GMP-AMP synthase (cGAS). The release of IFN-β was dramatically reduced when mtDNA-cGAS-STING pathway inhibited. STING mice showed milder periapical bone loss and lower serum IFN-β levels compared with wildtype mice after 28 days F. nucleatum-infected pulpitis model establishment. Our data demonstrated that F. nucleatum exacerbated the progression of pulpitis, which was mediated by the STING-dependent pathway.
Topics: Mice; Rats; Animals; Fusobacterium nucleatum; Signal Transduction; Pulpitis; RNA, Ribosomal, 16S; Nucleotidyltransferases; DNA, Mitochondrial
PubMed: 38085169
DOI: 10.1096/fj.202301648R -
Zhonghua Liu Xing Bing Xue Za Zhi =... Nov 2020With the development of multi-omics and high throughput sequencing technology, studies have shown that the disorder of microbiota is related to various cancers.... (Review)
Review
With the development of multi-omics and high throughput sequencing technology, studies have shown that the disorder of microbiota is related to various cancers. Nevertheless, the research on the relationship between upper digestive tract cancer or precancerous lesions and gastrointestinal microecology is still less. , one of the oral symbiotic bacteria, is also an opportunistic pathogen, which can promote the formation of tumor microenvironment and can be used as a new biomarker for the early detection and early diagnosis of cancer. In this study, by searching CNKI, Wanfang data, PubMed and Embase databases, it was found that the abundance of in cancer tissues is higher than that in paracancerous tissues and associated with poor prognosis. The research of relationship between and precancerous lesions needs to be carried out urgently. In addition, the types of specimens, sequencing technology, strain subtypes, carcinogenic mechanism and other directions still need to be explored.
Topics: Fusobacterium nucleatum; Gastrointestinal Neoplasms; Humans
PubMed: 33297665
DOI: 10.3760/cma.j.cn112338-20191102-00776