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Journal of Materials Chemistry. B Apr 2024Colorectal cancer (CRC) occurs in the colorectum and ranks second in the global incidence of all cancers, accounting for one of the highest mortalities. Although the...
Engineering lauric acid-based nanodrug delivery systems for restoring chemosensitivity and improving biocompatibility of 5-FU and OxPt against -associated colorectal tumor.
Colorectal cancer (CRC) occurs in the colorectum and ranks second in the global incidence of all cancers, accounting for one of the highest mortalities. Although the combination chemotherapy regimen of 5-fluorouracil (5-FU) and platinum(IV) oxaliplatin prodrug (OxPt) is an effective strategy for CRC treatment in clinical practice, chemotherapy resistance caused by tumor-resided () could result in treatment failure. To enhance the efficacy and improve the biocompatibility of combination chemotherapy, we developed an antibacterial-based nanodrug delivery system for -associated CRC treatment. A tumor microenvironment-activated nanomedicine 5-FU-LA@PPL was constructed by the self-assembly of chemotherapeutic drug derivatives 5-FU-LA and polymeric drug carrier PPL. PPL is prepared by conjugating lauric acid (LA) and OxPt to hyperbranched polyglycidyl ether. In principle, LA is used to selectively combat , inhibit autophagy in CRC cells, restore chemosensitivity of 5-FU as well as OxPt, and consequently enhance the combination chemotherapy effects for -associated drug-resistant colorectal tumor. Both and studies exhibited that the tailored nanomedicine possessed efficient antibacterial and anti-tumor activities with improved biocompatibility and reduced non-specific toxicity. Hence, this novel anti-tumor strategy has great potential in the combination chemotherapy of CRC, which suggests a clinically relevant valuable option for bacteria-associated drug-resistant cancers.
Topics: Fluorouracil; Colorectal Neoplasms; Humans; Lauric Acids; Animals; Mice; Antineoplastic Agents; Fusobacterium nucleatum; Oxaliplatin; Drug Delivery Systems; Cell Proliferation; Drug Screening Assays, Antitumor; Prodrugs; Biocompatible Materials; Anti-Bacterial Agents; Mice, Inbred BALB C; Particle Size; Drug Carriers
PubMed: 38586917
DOI: 10.1039/d4tb00103f -
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 -
BMC Veterinary Research Apr 2024Periodontitis is the most common oral disease in dogs, and its progression and severity are influenced by risk factors, such as age and body size. Recent studies have...
BACKGROUND
Periodontitis is the most common oral disease in dogs, and its progression and severity are influenced by risk factors, such as age and body size. Recent studies have assessed the canine oral microbiota in relation to different stages of periodontitis and niches within the oral cavity. However, knowledge of the bacterial composition at different ages and body sizes, especially in puppies, is limited. This study aimed to characterize the oral microbiota in the healthy gingiva of small breed puppies using next-generation sequencing. Additionally, we assessed the impact of dental care practices and the presence of retained deciduous teeth on the oral microbiota.
RESULTS
In this study, plaque samples were collected from the gingival margin of 20 small breed puppies (age, 6.9 ± 0.6 months). The plaque samples were subjected to next-generation sequencing targeting the V3-V4 region of the 16 S rRNA. The microbiota of the plaque samples was composed mostly of gram-negative bacteria, primarily Proteobacteria (54.12%), Bacteroidetes (28.79%), and Fusobacteria (5.11%). Moraxella sp. COT-017, Capnocytophaga cynodegmi COT-254, and Bergeyella zoohelcum COT-186 were abundant in the oral cavity of the puppies. In contrast, Neisseria animaloris were not detected. The high abundance of Pasteurellaceae suggests that this genus is characteristic of the oral microbiota in puppies. Dental care practices and the presence of retained deciduous teeth showed no effects on the oral microbiota.
CONCLUSIONS
In this study, many bacterial species previously reported to be detected in the normal oral cavity of adult dogs were also detected in 6-8-month-old small breed dogs. On the other hand, some bacterial species were not detected at all, while others were detected in high abundance. These data indicate that the oral microbiota of 6-8-month-old small breed dogs is in the process of maturating in to the adult microbiota and may also have characteristics of the small dog oral microbiota.
Topics: Dogs; Animals; RNA, Ribosomal, 16S; Gingiva; Periodontitis; Microbiota; Bacteria; Dog Diseases
PubMed: 38580990
DOI: 10.1186/s12917-024-03973-5 -
The Journal of Nutritional Biochemistry Jul 2024Adequate dietary L-tryptophan (Trp) governs intestinal homeostasis in piglets. However, the defensive role of Trp in the diet against enterotoxigenic Escherichia coli F4...
Dietary tryptophan improves growth and intestinal health by promoting the secretion of intestinal β-defensins against enterotoxigenic Escherichia coli F4 in weaned piglets.
Adequate dietary L-tryptophan (Trp) governs intestinal homeostasis in piglets. However, the defensive role of Trp in the diet against enterotoxigenic Escherichia coli F4 (K88) in pigs is still poorly understood. Here, sixty (6.15 ± 1.52 kg, 24-day-old, Duroc × Landrace × Yorkshire) weaned piglets were used for an E. coli F4 attack test in a 2 × 2 factorial design. The growth (ADG, ADFI, GH), immune factors (IL-10, IgA, IgG, IgM), Trp metabolite 5-HT, intestinal morphology (jejunal and colonic VH), mRNA expression of β-defensins (jejunal BD-127, BD-119, ileal BD-1, BD-127), and abundance of beneficial microorganisms in the colon (Prevotella 9, Lactobacillus, Phascolarctobacterium, Faecalibacterium) were higher in the piglets in the HT (High Trp) and HTK (High Trp, K88) groups than in the LT (Low Trp) and LTK (Low Trp, K88) groups (P<.05), while FCR, diarrhea rate, diarrhea index, serum Trp, Kyn, IDO, D-LA, ET, and abundance of harmful microorganisms in the colon (Spirochaetes, Fusobacteria, Prevotella, Christensenellaceae R7) were lower in the HT and HTK groups than in the LT and LTK groups (P<.05). High Trp reduced the expression of virulence genes (K88 and LT) after E. coli F4 attack (P<.05). The IL-6, TNF-α was lower in the HTK group than in the LT, LTK group (P<.05). In short, a diet containing 0.35% Trp protected piglets from enterotoxigenic E. coli F4 (K88) via Trp metabolism promoting BD expression in the intestinal mucosa, which improved growth and intestinal health.
Topics: Animals; Tryptophan; Enterotoxigenic Escherichia coli; Swine; beta-Defensins; Weaning; Escherichia coli Infections; Swine Diseases; Intestines; Animal Feed; Gastrointestinal Microbiome; Intestinal Mucosa; Diet
PubMed: 38574828
DOI: 10.1016/j.jnutbio.2024.109637 -
Food & Function Apr 2024The oral cavity connects the external environment and the respiratory and digestive systems, and the oral microbial ecosystem is complex and plays a crucial role in... (Randomized Controlled Trial)
Randomized Controlled Trial
The oral cavity connects the external environment and the respiratory and digestive systems, and the oral microbial ecosystem is complex and plays a crucial role in overall health and immune defense against external threats. Recently, the potential use of probiotics for disease prevention and treatment has gained attention. This study aimed to assess the effect of CMS1 ( CMS1) consumption on the oral microbiome and immune function in healthy individuals through a 12-week clinical trial. This randomized, double-blind, placebo-controlled, parallel trial enrolled 90 healthy subjects. The consumption of CMS1 significantly increased salivary immunoglobulin A ( = 0.046) and decreased tumor necrosis factor-α (TNF-α) levels ( = 0.008). Analysis of the oral microbiota revealed changes in beta diversity, increased abundance of Firmicutes and Actinobacteria, and decreased abundance of Bacteroidetes and Fusobacteria after 12 weeks of consuming CMS1. Significant increases in various strains, including Lactobacillales, Bacilli, Streptococcaceae, Streptococcus, and Firmicutes, were observed in the CMS1 group after 12 weeks of intake. Additionally, and exhibited a positive correlation with TNF-α. These findings demonstrate the positive effect of CMS1 on the oral environment and immune function.
Topics: Humans; Probiotics; Weissella; Double-Blind Method; Male; Female; Adult; Mouth; Young Adult; Tumor Necrosis Factor-alpha; Microbiota; Saliva; Immunoglobulin A; Bacteria; Middle Aged
PubMed: 38563257
DOI: 10.1039/d4fo00195h -
Fish & Shellfish Immunology Jun 2024Skin mucus analysis has recently been used as a non-invasive method to evaluate for fish welfare. The present research study was conducted to examine the skin mucosal...
Skin mucus analysis has recently been used as a non-invasive method to evaluate for fish welfare. The present research study was conducted to examine the skin mucosal immunity and skin microbiota profiles of sturgeons infected with Citrobacter freundii. Our histology results showed that the thickness of the epidermal layer of skin remained thinner, and the number of mucous cells was significantly decreased in sturgeons after infection (p < 0.05). Total protein, alanine aminotransferase, aspartate aminotransferase, superoxide dismutase, and creatine kinase levels in the mucus showed biphasic pattern (decrease and then increase). Lactate dehydrogenase, lysozyme, and acid phosphatase activities in the mucus showed an increasing trend after infection. Furthermore, 16S rRNA sequencing also revealed that C. freundii infection also affected the diversity and community structure of the skin mucus microbiota. An increase in microbial diversity (p > 0.05) and a decrease in microbial abundance (p < 0.05) after infection were noted. The predominant bacterial phyla in the skin mucus were Proteobacteria, Fusobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Specifically, the relative abundance of Fusobacteria increased after infection. The predominant bacterial genera in the skin mucus were Cetobacterium, Pelomonas, Bradyrhizobium, Flavobacterium, and Pseudomonas. The relative abundance of Cetobacterium, Pseudomonas, and Flavobacterium increased after infection. Our current research findings will provide new insights into the theoretical basis for future research studies exploring the mechanism of sturgeon infection with C. freundii.
Topics: Animals; Citrobacter freundii; Microbiota; Fish Diseases; Skin; Fishes; Immunity, Mucosal; Enterobacteriaceae Infections; Mucus; RNA, Ribosomal, 16S
PubMed: 38561068
DOI: 10.1016/j.fsi.2024.109527 -
Physiological Genomics Jun 2024Short-chain fatty acids (SCFAs) produced by the gut bacteria have been associated with cardiovascular dysfunction in humans and rodents. However, studies exploring...
Short-chain fatty acids (SCFAs) produced by the gut bacteria have been associated with cardiovascular dysfunction in humans and rodents. However, studies exploring effects of SCFAs on cardiovascular parameters in the zebrafish, an increasingly popular model in cardiovascular research, remain limited. Here, we performed fecal bacterial 16S sequencing and gas chromatography/mass spectrometry (GC-MS) to determine the composition and abundance of gut microbiota and SCFAs in adult zebrafish. Following this, the acute effects of major SCFAs on heart rate and vascular tone were measured in anesthetized zebrafish larvae using fecal concentrations of butyrate, acetate, and propionate. Finally, we investigated if coincubation with butyrate may lessen the effects of angiotensin II (ANG II) and phenylephrine (PE) on vascular tone in anesthetized zebrafish larvae. We found that the abundance in , , and phyla in the adult zebrafish resembled those reported in rodents and humans. SCFA levels with highest concentration of acetate (27.43 µM), followed by butyrate (2.19 µM) and propionate (1.65 µM) were observed in the fecal samples of adult zebrafish. Immersion in butyrate and acetate produced a ∼20% decrease in heart rate (HR), respectively, with no observed effects of propionate. Butyrate alone also produced an ∼25% decrease in the cross-sectional width of the dorsal aorta (DA) at 60 min (* < 0.05), suggesting compensatory vasoconstriction, with no effects of either acetate or propionate. In addition, butyrate significantly alleviated the decrease in DA cross-sectional width produced by both ANG II and PE. We demonstrate the potential for zebrafish in investigation of host-microbiota interactions in cardiovascular health. We highlight the presence of a core gut microbiota and demonstrate in vivo short-chain fatty acid production in adult zebrafish. In addition, we show cardio-beneficial vasoactive and chronotropic properties of butyrate, and chronotropic properties of acetate in anesthetized zebrafish larvae.
Topics: Animals; Zebrafish; Gastrointestinal Microbiome; Fatty Acids, Volatile; Larva; Heart Rate; Feces; Butyrates; Angiotensin II; Bacteria; Phenylephrine; Acetates; RNA, Ribosomal, 16S
PubMed: 38557279
DOI: 10.1152/physiolgenomics.00013.2024 -
The Journal of Clinical Pediatric... Mar 2024In this case-control study, we aimed to investigate the specific oral pathogens potentially associated with the mobile microbiome in children with congenital heart...
In this case-control study, we aimed to investigate the specific oral pathogens potentially associated with the mobile microbiome in children with congenital heart disease (CHD). Caries, oral hygiene and gingival indices were evaluated in 20 children with CHD and a healthy control group, and venous blood samples and saliva were collected. Using quantitative polymerase chain reaction (qPCR), blood samples were analyzed for the presence of bacterial DNA to determine the mobile microbiome, and saliva samples were analyzed to identify and quantify target microorganisms, including () and its serotype (), (), (), () and () and its JP2 clone (). The findings were analyzed by Mann Whitney U, chi-square, Fisher's exact and Spearman's Correlation tests. Bacterial DNA was identified in two blood samples. No significant differences were found between the groups regarding the presence and counts of bacteria in saliva. However, the CHD group exhibited significantly lower caries and higher gingival index scores than the control group. The presence of and were significantly associated with higher gingival index scores. and counts were significantly correlated with caries experience. A positive correlation was found between and total bacteria counts. In conclusion, the mobile microbiome, which has been proposed as a potential marker of dysbiosis at distant sites, was very rare in our pediatric population. The counts of target microorganisms which are potentially associated with the mobile microbiome did not differ in children with CHD and healthy children.
Topics: Humans; Child; DNA, Bacterial; Case-Control Studies; Saliva; Heart Defects, Congenital; Porphyromonas gingivalis; Dental Caries; Streptococcus mutans; Fusobacterium nucleatum; Microbiota
PubMed: 38548632
DOI: 10.22514/jocpd.2024.026 -
Microbial Genomics Mar 2024The aetiological mechanisms of in laryngeal cancer remain unclear. This study aimed to reveal the epigenetic signature induced by in laryngeal squamous cell carcinoma...
The aetiological mechanisms of in laryngeal cancer remain unclear. This study aimed to reveal the epigenetic signature induced by in laryngeal squamous cell carcinoma (LSCC). Combined analysis of methylome and transcriptome data was performed to address the functional role of in laryngeal cancer. Twenty-nine differentially expressed methylation-driven genes were identified by mapping the methylation levels of significant differential methylation sites to the expression levels of related genes. The combined analysis revealed that promoted Janus kinase 3 (JAK3) gene expression in LSCC. Further validation found decreased methylation and elevated expression of JAK3 in the treated LSCC cell group; abundance and JAK3 gene expression had a positive correlation in tumour tissues. This analysis provides a novel understanding of the impact of in the methylome and transcriptome of laryngeal cancer. Identification of these epigenetic regulatory mechanisms opens up new avenues for mechanistic studies to explore novel therapeutic strategies.
Topics: Humans; Epigenome; Fusobacterium nucleatum; Laryngeal Neoplasms; Epigenesis, Genetic; Gene Expression Profiling
PubMed: 38536233
DOI: 10.1099/mgen.0.001221 -
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