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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 -
Infection and Immunity Aug 2023Fusobacterium nucleatum colonization contributes to the occurrence of portal vein thrombosis in patients with gastric cancer (GC). However, the underlying mechanism by...
Fusobacterium nucleatum colonization contributes to the occurrence of portal vein thrombosis in patients with gastric cancer (GC). However, the underlying mechanism by which F. nucleatum promotes thrombosis remains unclear. In this study, we recruited a total of 91 patients with GC and examined the presence of F. nucleatum in tumor and adjacent non-tumor tissues by fluorescence hybridization and quantitative PCR. Neutrophil extracellular traps (NETs) were detected by immunohistochemistry. Extracellular vesicles (EVs) were extracted from the peripheral blood and proteins in the EVs were identified by mass spectrometry (MS). HL-60 cells differentiated into neutrophils were used to package engineered EVs to imitate the EVs released from NETs. Hematopoietic progenitor cells (HPCs) and K562 cells were used for megakaryocyte (MK) differentiation and maturation to examine the function of EVs. We observed that F. nucleatum-positive patients had increased NET and platelet counts. EVs from F. nucleatum-positive patients could promote the differentiation and maturation of MKs and had upregulated 14-3-3 proteins, especially 14-3-3ε. 14-3-3ε upregulation promoted MK differentiation and maturation . HPCs and K562 cells could receive 14-3-3ε from the EVs, which interacted with GP1BA and 14-3-3ζ to trigger PI3K-Akt signaling. In conclusion, we identified for the first time that F. nucleatum infection promotes NET formation, which releases EVs containing 14-3-3ε. These EVs could deliver 14-3-3ε to HPCs and promote their differentiation into MKs via activation of PI3K-Akt signaling.
Topics: Humans; Fusobacterium nucleatum; Stomach Neoplasms; In Situ Hybridization, Fluorescence; 14-3-3 Proteins; Megakaryocytes; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Fusobacterium Infections; Extracellular Vesicles
PubMed: 37404144
DOI: 10.1128/iai.00102-23 -
Journal of Nanobiotechnology Feb 2024A large number of Fusobacterium nucleatum (Fn) are present in colorectal cancer (CRC) tissues of patients who relapse after chemotherapy, and Fn has been reported to...
BACKGROUND
A large number of Fusobacterium nucleatum (Fn) are present in colorectal cancer (CRC) tissues of patients who relapse after chemotherapy, and Fn has been reported to promote oxaliplatin and 5-FU chemoresistance in CRC. Pathogens such as bacteria and parasites stimulate exosome production in tumor cells, and the regulatory mechanism of exosomal circRNA in the transmission of oxaliplatin and 5-FU chemotherapy resistance in Fn-infected CRC remains unclear.
METHODS
Hsa_circ_0004085 was screened by second-generation sequencing of CRC tissues. The correlation between hsa_circ_0004085 and patient clinical response to oxaliplatin/5-FU was analyzed. Exosome tracing experiments and live imaging systems were used to test the effect of Fn infection in CRC on the distribution of hsa_circ_0004085. Colony formation, ER tracking analysis and immunofluorescence were carried out to verify the regulatory effect of exosomes produced by Fn-infected CRC cells on chemotherapeutic resistance and ER stress. RNA pulldown, LC-MS/MS analysis and RIP were used to explore the regulatory mechanism of downstream target genes by hsa_circ_0004085.
RESULTS
First, we screened out hsa_circ_0004085 with abnormally high expression in CRC clinical samples infected with Fn and found that patients with high expression of hsa_circ_0004085 in plasma had a poor clinical response to oxaliplatin/5-FU. Subsequently, the circular structure of hsa_circ_0004085 was identified. Fn infection promoted hsa_circ_0004085 formation by hnRNP L and packaged hsa_circ_0004085 into exosomes by hnRNP A1. Exosomes produced by Fn-infected CRC cells transferred hsa_circ_0004085 between cells and delivered oxaliplatin/5-FU resistance to recipient cells by relieving ER stress. Hsa_circ_0004085 enhanced the stability of GRP78 mRNA by binding to RRBP1 and promoted the nuclear translocation of ATF6p50 to relieve ER stress.
CONCLUSIONS
Plasma levels of hsa_circ_0004085 are increased in colon cancer patients with intracellular Fn and are associated with a poor response to oxaliplatin/5-FU. Fn infection promoted hsa_circ_0004085 formation by hnRNP L and packaged hsa_circ_0004085 into exosomes by hnRNP A1. Exosomes secreted by Fn-infected CRC cells deliver hsa_circ_0004085 between cells. Hsa_circ_0004085 relieves ER stress in recipient cells by regulating GRP78 and ATF6p50, thereby delivering resistance to oxaliplatin and 5-FU.
Topics: Humans; Oxaliplatin; Fusobacterium nucleatum; Heterogeneous Nuclear Ribonucleoprotein A1; Colorectal Neoplasms; Exosomes; Chromatography, Liquid; Endoplasmic Reticulum Chaperone BiP; Heterogeneous-Nuclear Ribonucleoprotein L; Tandem Mass Spectrometry; Colonic Neoplasms; Fluorouracil; MicroRNAs; Cell Proliferation
PubMed: 38360615
DOI: 10.1186/s12951-024-02331-9 -
Molecular Medicine (Cambridge, Mass.) Sep 2023Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention...
BACKGROUND
Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM.
METHODS
GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels.
RESULTS
GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-β and IL-10, preventing inflammation and preserving mouse pregnancy.
CONCLUSION
Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health.
Topics: Female; Pregnancy; Humans; Animals; Mice; B-Lymphocytes, Regulatory; Asparagine; Aspartic Acid; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dysbiosis; Leptin; T-Lymphocytes, Regulatory; Inflammation
PubMed: 37684563
DOI: 10.1186/s10020-023-00716-4 -
Cardiovascular Diabetology Apr 2024Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic...
BACKGROUND
Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia-reperfusion injury (MIRI).
METHODS
We comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice.
RESULTS
Specific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI.
CONCLUSION
Our findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.
Topics: Humans; Animals; Mice; Gastrointestinal Microbiome; Mice, Inbred C57BL; Fusobacterium nucleatum; Coronary Artery Disease; Diabetes Mellitus
PubMed: 38581039
DOI: 10.1186/s12933-024-02217-y -
Gut Microbes 2024Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the functional implications...
Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the functional implications of host-microbe interactions in CRC are scarce. Therefore, we characterized the influence of CRC core pathogens and biofilms on the tumor microenvironment (TME) in 40 CRC, paired normal, and healthy tissue biopsies using fluorescence hybridization (FISH) and dual-RNA sequencing. FISH revealed that . was associated with increased bacterial biomass and inflammatory response in CRC samples. Dual-RNA sequencing demonstrated increased expression of pro-inflammatory cytokines, defensins, matrix-metalloproteases, and immunomodulatory factors in CRC samples with high bacterial activity. In addition, bacterial activity correlated with the infiltration of several immune cell subtypes, including M2 macrophages and regulatory T-cells in CRC samples. Specifically, and correlated with the infiltration of neutrophils and CD4 T-cells, respectively. The collective bacterial activity/biomass appeared to exert a more significant influence on the TME than core pathogens, underscoring the intricate interplay between gut microbiota and CRC. These results emphasize how biofilms and core pathogens shape the immune phenotype and TME in CRC while highlighting the need to extend the bacterial scope beyond CRC pathogens to advance our understanding and identify treatment targets.
Topics: Colorectal Neoplasms; Humans; Biofilms; Tumor Microenvironment; Gastrointestinal Microbiome; Male; Female; Bacteria; Middle Aged; In Situ Hybridization, Fluorescence; Aged; Fusobacterium nucleatum; Cytokines; Macrophages; Phenotype; Bacteroides fragilis
PubMed: 38726597
DOI: 10.1080/19490976.2024.2350156 -
Gut Microbes 2024Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific...
Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that could inhibit pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.
Topics: Humans; Fusobacterium nucleatum; Colorectal Neoplasms; Hippo Signaling Pathway; Drug Resistance, Neoplasm; Pyroptosis; Gastrointestinal Microbiome; Neoplasm Recurrence, Local
PubMed: 38533566
DOI: 10.1080/19490976.2024.2333790 -
Scientific Reports Oct 2023Bacterial communities play an important role in mangrove ecosystems. In order to gain information on the bacterial communities in mangrove species and rhizospheres grown...
Bacterial communities play an important role in mangrove ecosystems. In order to gain information on the bacterial communities in mangrove species and rhizospheres grown in Zhangjiangkou National Mangrove Nature Reserve, this study collected root, branch, and leaf samples from five mangrove species as well as rhizosphere and non-rhizosphere samples and analyzed the community structure of endophytic bacteria and bacteria in rhizosphere and non-rhizosphere using Illumina high-throughput sequencing technique. Bacteria in 52 phyla, 64 classes, 152 orders, 295 families, and 794 genera were identified, which mainly belonged to Proteobacteria, Cyanobacteria, Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Nitrospirota. At each taxonomic level, the community structure of the rhizosphere bacteria varied slightly with mangrove species, but endophytic bacteria differed greatly with plant species. The diversity indices of endophytic bacteria in branch and leaf samples of Acanthus ilicifolius were significantly lower, and endophytic bacteria in the plant tissues had higher abundance in the replication/repair and translation Clusters of Orthologous Genes functional categories but lower abundance in the carbohydrate metabolism category. This study helps to understand the community structure and diversity characteristics of endophytic and rhizosphere bacteria in different mangrove plants. Provide a theoretical basis for in-depth research on the functions of mangrove ecosystems.
Topics: Humans; Ecosystem; Rhizosphere; RNA, Ribosomal, 16S; Cyanobacteria; Proteobacteria; Soil Microbiology
PubMed: 37816825
DOI: 10.1038/s41598-023-44447-2 -
Potential role of epithelial-mesenchymal transition induced by periodontal pathogens in oral cancer.Journal of Cellular and Molecular... Jan 2024With the increasing incidence of oral cancer in the world, it has become a hotspot to explore the pathogenesis and prevention of oral cancer. It has been proved there is... (Review)
Review
With the increasing incidence of oral cancer in the world, it has become a hotspot to explore the pathogenesis and prevention of oral cancer. It has been proved there is a strong link between periodontal pathogens and oral cancer. However, the specific molecular and cellular pathogenic mechanisms remain to be further elucidated. Emerging evidence suggests that periodontal pathogens-induced epithelial-mesenchymal transition (EMT) is closely related to the progression of oral cancer. Cells undergoing EMT showed increased motility, aggressiveness and stemness, which provide a pro-tumour environment and promote malignant metastasis of oral cancer. Plenty of studies proposed periodontal pathogens promote carcinogenesis via EMT. In the current review, we discussed the association between the development of oral cancer and periodontal pathogens, and summarized various mechanisms of EMT caused by periodontal pathogens, which are supposed to play an important role in oral cancer, to provide targets for future research in the fight against oral cancer.
Topics: Humans; Porphyromonas gingivalis; Mouth Neoplasms; Epithelial-Mesenchymal Transition; Carcinogenesis; Fusobacterium nucleatum
PubMed: 38031653
DOI: 10.1111/jcmm.18064 -
Microbiome Jan 2024Aquaculture plays an important role in global protein supplies and food security. The ban on antibiotics as feed additive proposes urgent need to develop alternatives....
BACKGROUND
Aquaculture plays an important role in global protein supplies and food security. The ban on antibiotics as feed additive proposes urgent need to develop alternatives. Gut microbiota plays important roles in the metabolism and immunity of fish and has the potential to give rise to novel solutions for challenges confronted by fish culture. However, our understanding of fish gut microbiome is still lacking.
RESULTS
We identified 575,856 non-redundant genes by metagenomic sequencing of the intestinal content samples of grass carp. Taxonomic and functional annotation of the gene catalogue revealed specificity of the gut microbiome of grass carp compared with mammals. Co-occurrence analysis indicated exclusive relations between the genera belonging to Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes, suggesting two independent ecological groups of the microbiota. The association pattern of Proteobacteria with the gene expression modules of fish gut and the liver was consistently opposite to that of Fusobacteria, Firmicutes, and Bacteroidetes, implying differential functionality of Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes. Therefore, the two ecological groups were considered as two functional groups, i.e., Functional Group 1: Proteobacteria and Functional Group 2: Fusobacteria/Firmicutes/Bacteroidetes. Further analysis revealed that the two functional groups differ in genetic capacity for carbohydrate utilization, virulence factors, and antibiotic resistance. Finally, we proposed that the ratio of "Functional Group 2/Functional Group 1" can be used as a biomarker that efficiently reflects the structural and functional characteristics of the microbiota of grass carp.
CONCLUSIONS
The gene catalogue is an important resource for investigating the gut microbiome of grass carp. Multi-omics analysis provides insights into functional implications of the main phyla that comprise the fish microbiota and shed lights on targets for microbiota regulation. Video Abstract.
Topics: Animals; Gastrointestinal Microbiome; Carps; Multiomics; Microbiota; Proteobacteria; Fusobacteria; Bacteroidetes; Firmicutes; Fusobacterium; RNA, Ribosomal, 16S; Mammals
PubMed: 38167330
DOI: 10.1186/s40168-023-01715-7