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BMC Cancer Oct 2023To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC).
BACKGROUND
To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC).
METHODS
The prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins.
RESULTS
Fn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH, which could be proven by HO assay and N-acetylcysteine.
CONCLUSIONS
Higher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.
Topics: Humans; MicroRNAs; Fusobacterium nucleatum; Squamous Cell Carcinoma of Head and Neck; 8-Hydroxy-2'-Deoxyguanosine; Hydrogen Peroxide; Reactive Oxygen Species; Retrospective Studies; Cell Line, Tumor; Cell Proliferation; Oxidative Stress; Head and Neck Neoplasms; Autophagy; Gene Expression Regulation, Neoplastic
PubMed: 37848855
DOI: 10.1186/s12885-023-11439-4 -
Microbiology Spectrum Dec 2023Colorectal cancer (CRC) is the second most common cancer in the world; the main treatment for CRC is immunosuppressive therapy, but this therapy is only effective for a...
Colorectal cancer (CRC) is the second most common cancer in the world; the main treatment for CRC is immunosuppressive therapy, but this therapy is only effective for a small percentage of CRC patients, so there is an urgent need for a treatment with fewer side effects and higher efficacy. This study demonstrated that with increased abundance in CRC can regulate the autophagy process and disrupt normal intestinal microbiota by producing hydrogen sulfide, factors that may be involved in the development and progression of CRC. This study may provide a reference for future CRC treatment options that are efficient and have fewer side effects.
Topics: Humans; Fusobacterium nucleatum; Colorectal Neoplasms; Gastrointestinal Microbiome; Hydrogen Sulfide; Autophagy
PubMed: 37889013
DOI: 10.1128/spectrum.02292-23 -
Journal of Medicinal Chemistry Dec 2023Recent studies revealed that intestinal microbiota played important roles in colorectal cancer (CRC) carcinogenesis. Particularly, was confirmed to promote the...
Recent studies revealed that intestinal microbiota played important roles in colorectal cancer (CRC) carcinogenesis. Particularly, was confirmed to promote the proliferation and metastasis of CRC. Therefore, targeting may be a potential preventive and therapeutic approach for CRC. Herein, 2,272 off-patent drugs were screened inhibitory activity against . Among the hits, nitisinone was identified as a promising anti- lead compound. Further optimization of nitisinone led to the discovery of more potent derivatives. Particularly, compounds and showed potent anti- activity (MIC = 1 and 2 μg/mL, respectively) with low cytotoxicity. Among them, compound effectively attenuated the migratory ability of MC-38 cells induced by . Preliminary mechanism studies suggested that nitisinone and its derivatives might act by downregulating nitroreductase and tryptophanase. Thus, the development of small molecule inhibitors represents an effective strategy to treat CRC.
Topics: Humans; Fusobacterium nucleatum; Colorectal Neoplasms; Tryptophanase; Drug Repositioning; Colonic Neoplasms
PubMed: 37983010
DOI: 10.1021/acs.jmedchem.3c00281 -
International Journal of Molecular... Aug 2023The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing...
The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan-asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of strains and a decrease in the relative abundance of , with the presence of in the gut microbiota. was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.
Topics: Humans; Gastrointestinal Microbiome; Aspartate Aminotransferases; East Asian People; Liver Cirrhosis; Microbiota
PubMed: 37686272
DOI: 10.3390/ijms241713470 -
Frontiers in Oral Health 2024The study aimed to evaluate the impact of tobacco use on the composition and functions of the oral microbiome in healthy adult humans. (Review)
Review
OBJECTIVE
The study aimed to evaluate the impact of tobacco use on the composition and functions of the oral microbiome in healthy adult humans.
METHODS
We conducted a systematic search on PubMed, Web of Science, and Cinhal databases for literature published until 15 December 2023, to identify studies that have evaluated the oral microbiome with culture-independent next-generation techniques comparing the oral microbiome of tobacco users and non-users. The search followed the PECO format. The outcomes included changes in microbial diversity and abundance of microbial taxa. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS) (PROSPERO ID CRD42022340151).
RESULTS
Out of 2,435 articles screened, 36 articles satisfied the eligibility criteria and were selected for full-text review. Despite differences in design, quality, and population characteristics, most studies reported an increase in bacterial diversity and richness in tobacco users. The most notable bacterial taxa enriched in users were and at the phylum level and , , and at the genus level. At the functional level, more similarities could be noted; and were increased in tobacco users compared to non-users. Most of the studies were of good quality on the NOS scale.
CONCLUSION
Tobacco smoking influences oral microbial community harmony, and it shows a definitive shift towards a proinflammatory milieu. Heterogeneities were detected due to sampling and other methodological differences, emphasizing the need for greater quality research using standardized methods and reporting.
SYSTEMATIC REVIEW REGISTRATION
CRD42022340151.
PubMed: 38445094
DOI: 10.3389/froh.2024.1310334 -
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 -
European Journal of Clinical... Jan 2024Renew interest and enthusiasm for anaerobes stem from both technological improvements (culture media, production of an adequate anaerobic atmosphere, identification... (Review)
Review
Renew interest and enthusiasm for anaerobes stem from both technological improvements (culture media, production of an adequate anaerobic atmosphere, identification methods) and greater awareness on the part of clinicians. Anaerobic infections were historically treated empirically, targeting the species known to be involved in each type of infection. Prevotella, fusobacteria, and Gram-positive cocci (GPAC) were considered responsible for infections above the diaphragm whereas for intra-abdominal infections, Bacteroides of the fragilis group (BFG), GPAC and clostridia were predominantly implicated. The antibiotic susceptibility of anaerobes was only taken into consideration by the clinician in the event of treatment failure or when faced with infections by multidrug-resistant bacteria (MDR). The evolution of antibiotic resistance together with clinical failures due to the absence of detection of hetero-resistant clones has resulted in a greater need for accessible antibiotic susceptibility testing (AST) and disc diffusion method. Improved isolation and identification of anaerobes, along with the availability of accessible and robust methods for performing AST, will ensure that treatment, whether empirical or guided by an antibiogram, will lead to better outcomes for anaerobic infections.
Topics: Humans; Drug Resistance, Bacterial; Bacteria, Anaerobic; Clostridium; Microbial Sensitivity Tests; Gram-Positive Cocci; Anti-Bacterial Agents; Bacterial Infections
PubMed: 37973693
DOI: 10.1007/s10096-023-04708-4 -
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 -
Immunity, Inflammation and Disease Nov 2023Colorectal cancer (CRC) represents a leading cause of cancer-related deaths. Metronidazole (MNZ) is exceedingly implicated in CRC. This study explored the roles of MNZ...
OBJECTIVE
Colorectal cancer (CRC) represents a leading cause of cancer-related deaths. Metronidazole (MNZ) is exceedingly implicated in CRC. This study explored the roles of MNZ in mouse CRC occurrence and liver metastasis (CRLM).
METHODS
Male BALB/c nude mice were subjected to CRC and CRLM modeling, orally administration with MNZ (1 g/L) 1 week before modeling, and disease activity index (DAI) evaluation. Fresh stool and anal swab samples were collected on the morning of the 28th day after modeling. The relative expression of Fusobacterium nucleatum (F. nucleatum) DNA was assessed by quantitative polymerase chain reaction. After euthanasia, tumor tissues and liver tissues were separated and the tumor volume and weight change were measured. The liver tissues were stained with hematoxylin-eosin to quantitatively analyze the metastatic liver nodules. Malignant tumor biomarker Ki67 protein levels in liver tissues/DNA from stool samples were detected by immunohistochemistry/high-throughput 16S rRNA gene sequencing. Bioinformatics analysis was performed on the raw sequence data to analyze microbial community richness (Chao1 index, ACE index) and microbial community diversity (Shannon index).
RESULTS
The DAI and F. nucleatum DNA relative expression in feces and anal swabs of the CRC and CRLM groups were raised and repressed after MNZ intervention. MNZ repressed tumor occurrence and growth in mice to a certain extent, alleviated CRLM malignant degree (reduced liver metastases and Ki67-positive cell density/number), and suppressed CRC liver metastasis by regulating intestinal flora structure, which affected the intestinal characteristic flora of CRC and CRLM mice.
CONCLUSION
MNZ suppressed CRC occurrence and CRLM in mice by regulating intestinal F. nucleatum.
Topics: Male; Animals; Mice; Fusobacterium nucleatum; Colorectal Neoplasms; Metronidazole; Ki-67 Antigen; Mice, Nude; RNA, Ribosomal, 16S; Fusobacterium Infections; Liver Neoplasms; DNA
PubMed: 38018574
DOI: 10.1002/iid3.1067 -
Frontiers in Cellular and Infection... 2023The elevated mortality rate associated with non-small-cell lung cancer (NSCLC) is a well-established global concern. Considerable attention has been directed toward...
BACKGROUND
The elevated mortality rate associated with non-small-cell lung cancer (NSCLC) is a well-established global concern. Considerable attention has been directed toward exploring the association between gut microbiota and various malignant tumors. We herein investigated the associations between the intestinal microbiome and its metabolites, particularly short-chain fatty acids (SCFAs), in patients with NSCLC at different stages, including early and brain metastasis (BM) stages. The findings aim to offer a fresh perspective on the diagnosis and management of NSCLC.
METHODS
Fecal samples were collected from 115 participants, comprising healthy controls (n = 35) and patients with treatment-naive NSCLC at the early stage (ELC, n = 40) and the BM stage (n = 40). Characterization of the intestinal microbiome and fecal SCFA levels was performed using 16S rRNA gene sequencing and gas chromatography.
RESULTS
The microbial diversity in patients with NSCLC was found to be less abundant and uniform, particularly in the BM stage. Significant alterations in the community structure of the gut microbiota were observed in patients with NSCLC, with an increase in pathogens in Fusobacteria and Proteobacteria and a decrease in SCFA-producing bacteria in Firmicutes and Actinobacteria, particularly in the BM stage. Meanwhile, microbial communities displayed intricate associations in patients with NSCLC. A biomarker panel (, , , , , and ) successfully distinguished patients in the ELC and BM stages from healthy controls (area under the curve: 0.884). The overall concentration of fecal SCFAs was significantly lower in patients with BM compared to patients with ELC and healthy controls. Subgroup analysis of acetate and butyrate yielded similar results. Moreover, multiple disrupted pathways in the NSCLC group were identified using the Kyoto Encyclopedia of Genes and Genomes annotation, including lipid metabolism and genetic information processing, specifically in the BM stage.
CONCLUSION
Compared with healthy controls, distinct host-microbe interactions were evident in different phases of patients with NSCLC. Furthermore, specific forms of the gut microbiome and SCFAs may serve as valuable biomarkers and therapeutic targets in the diagnosis and treatment of NSCLC.
Topics: Humans; Gastrointestinal Microbiome; Carcinoma, Non-Small-Cell Lung; RNA, Ribosomal, 16S; Lung Neoplasms; Fatty Acids, Volatile; Bacteria; Feces; Brain Neoplasms
PubMed: 38304459
DOI: 10.3389/fcimb.2023.1211855