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Aging Nov 2023Evidence suggests that the tumor microenvironment (TME) affects the tumor active response to immunotherapy. Tumor angiogenesis is closely related to the TME....
BACKGROUND
Evidence suggests that the tumor microenvironment (TME) affects the tumor active response to immunotherapy. Tumor angiogenesis is closely related to the TME. Nonetheless, the effects of angiogenesis on the TME of colorectal cancer (CRC) remain unknown.
METHODS
We comprehensively assessed the angiogenesis patterns in CRC based on 36 angiogenesis-related genes (ARGs). Subsequently, we evaluated the prognostic values and therapeutic sensitivities of angiogenesis patterns using multiple methods. We then performed the machine learning algorithm and functional experiments to identify the prognostic key ARGs. Ultimately, the regulation of gut microbiota on the expression of ARGs was further investigated by using whole genome sequencing.
RESULTS
Two angiogenesis clusters were identified and angiogenesis cluster B was characterized by increased stromal and immunity activation with unfavorable odds of survival. Further, an ARG_score including 9 ARGs to predict recurrence-free survival (RFS) was established and its predominant predictive ability was confirmed. The low ARG_score patients were characterized by a high mutation burden, high microsatellite instability, and immune activation with better prognosis. Moreover, patients with high KLK10 expression were associated with a hot tumor immune microenvironment, poorer immune checkpoint blocking treatment, and shorter survival. The experiments also indicated that () infection significantly induced KLK10 expression in CRC.
CONCLUSIONS
The quantification of angiogenesis patterns could contribute to predict TME characteristics, prognosis, and individualized immunotherapy strategies. Furthermore, our findings suggest that may influence CRC progression through ARGs, which could serve as a clinical biomarker and therapeutic target for -infected CRC patients.
Topics: Humans; Prognosis; Immunotherapy; Algorithms; Cardiovascular Physiological Phenomena; Fusobacterium nucleatum; Tumor Microenvironment; Colorectal Neoplasms
PubMed: 37938164
DOI: 10.18632/aging.205189 -
Biochemical and Biophysical Research... Dec 2023Fusobacterium nucleatum (F. nucleatum) is an anaerobic gram-negative bacterium that was previously thought to be related to the progression of colorectal cancer. In F....
Fusobacterium nucleatum (F. nucleatum) is an anaerobic gram-negative bacterium that was previously thought to be related to the progression of colorectal cancer. In F. nucleatum, thiolase participates in fatty acid metabolism, and it can catalyse the transfer of an acetyl group from acetyl-CoA to another molecule, typically a fatty acid or another molecule in the synthesis of lipids. To gain deeper insight into the molecular mechanism governing the function of thiolase in F. nucleatum (Fn0495), we herein report the structure of Fn0495. The monomer of Fn0495 consists of three subdomains, namely, the N-terminal domain (residues 1-117 and 252-270), the C-terminal domain (residues 273-393), and the loop domain (residues 118-251). Fn0495 shows a unique difference in the charge and structure of the substrate binding pocket compared with homologous proteins. This research found three conserved residues (Cys88, His357, and Cys387) in Fn0495 arranged near a potential substrate binding pocket. In this study, the conformational changes between the covering loop, catalytic cysteine loop, regulatory determinant region, and homologous protein were compared. These results will enhance our understanding of the molecular characteristics and roles of the thiolase family.
Topics: Fusobacterium nucleatum; Acetyl-CoA C-Acetyltransferase; Acetyl Coenzyme A; Cysteine; Fatty Acids
PubMed: 37951156
DOI: 10.1016/j.bbrc.2023.149151 -
Frontiers in Oral Health 2024The human oral microbiome may play a role in the development of oral squamous cell carcinoma. The aim of this scoping review was to examine microbial diversity and... (Review)
Review
OBJECTIVES
The human oral microbiome may play a role in the development of oral squamous cell carcinoma. The aim of this scoping review was to examine microbial diversity and differences in the composition of the oral microbiome between OSCC patients and healthy controls.
METHODS
A literature search (in PubMed and Embase.com) was performed on January 9, 2023. The outcome variables used from the included studies of this review were alpha- and beta diversity and oral microbiome composition profiles for each taxonomic level (phylum-, class-, order-, genus- and species level).
RESULTS
Thirteen out of 423 studies were included in this review compromising 1,677 subjects, of which 905 (54.0%) were OSCC patients and 772 (46.0%) were healthy controls. Most studies found a higher alpha diversity in the OSCC patient group and significantly different beta diversities between OSCC patient samples and healthy control samples. Studies reported more abundant (on phylum level), (on genus level), and (on species level) in OSCC patients. The healthy control group had more abundant (on phylum level), and (on genus level) and (on species level) according to most studies.
CONCLUSIONS
Our findings show differences in oral microbiome diversity and composition in OSCC patients. Clinical implications demand continuing study. Development of internationally accepted standard procedures for oral sample collection and oral microbiota analysis is needed for more conclusive and clinically relevant comparisons in future research.
PubMed: 38919733
DOI: 10.3389/froh.2024.1366153 -
Heliyon Sep 2023Variations of cytokines and gut microbiota diversity with improved cognitive function in patients with obesity following bariatric surgery were poorly understood. The...
PURPOSE
Variations of cytokines and gut microbiota diversity with improved cognitive function in patients with obesity following bariatric surgery were poorly understood. The aim of this study was to testify the relationship among gut microbiota, cytokines and cognitive function in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG).
METHODS
Forty patients were enrolled in this study. Demographics, and serum and stool specimens were collected from all patients before and 3 months after LSG. The Montreal Cognitive Assessment (MoCA) scale, as well as assessment of immediate and delayed memory were used to evaluate self-perceived cognitive improvement after LSG.
RESULTS
LSG resulted in significant weight loss and improvement in cognitive functions, as measured by questionnaires. Bariatric surgery tended to increase gut microbiota relative abundance and diversity. The intestinal flora increased in the proportion of and phyla, and decreased in the proportion of , and phyla after LSG. Plasma IL-1β and TNF-α levels were significantly decreased following LSG, while IL-4 was significantly increased. MoCA test scores were significant correlated with IL-4, TNF-α and IL-1β. In addition, had a positive correlation with TNF-α, while had a negative correlation with IL-1β. was negatively correlated with IL-4.
CONCLUSION
Changes in gut microbiota were positive relationship with cognitive function improvement following LSG. Inflammation cytokines maybe played as a mediator between gut microbiota and cognitive function through gut-microbiota-brain axis.
PubMed: 37810155
DOI: 10.1016/j.heliyon.2023.e19245 -
Molecular Oral Microbiology Feb 2024Breast cancer is among the most prevalent malignancies in women worldwide. Epidemiological findings suggested that periodontal diseases may be associated with breast... (Review)
Review
Breast cancer is among the most prevalent malignancies in women worldwide. Epidemiological findings suggested that periodontal diseases may be associated with breast cancer, among which Fusobacterium nucleatum is considered an important cross-participant. In this work, we comprehensively summarize the known mechanisms of how F. nucleatum translocates to, colonizes in mammary tumors, and promotes the carcinogenesis. Specifically, F. nucleatum translocates to mammary tissue through the mammary-intestinal axis, direct nipple contact, and hematogenous transmission. Subsequently, F. nucleatum takes advantage of fusobacterium autotransporter protein 2 to colonize breast cancer and uses virulence factors fusobacterium adhesin A and lipopolysaccharide to promote proliferation. Moreover, the upregulated matrix metalloproteinase-9 induced by F. nucleatum does not only trigger the inflammatory response but also facilitates the tumor-promoting microenvironment. Aside from the pro-inflammatory effect, F. nucleatum may also be engaged in tumor immune evasion, which is achieved through the action of virulence factors on immune checkpoint receptors highly expressed on T cells, natural killer cells, and tumor-infiltrating lymphocytes. Taking breast cancer as an example, more relevant research studies may expand our current knowledge of how oral microbes affect systemic health. Hopefully, exploring these mechanisms in depth could provide new strategies for safer and more effective biologic and targeted therapies targeted at breast cancer.
Topics: Humans; Female; Fusobacterium nucleatum; Breast Neoplasms; Colorectal Neoplasms; Adhesins, Bacterial; Virulence Factors; Fusobacterium Infections; Tumor Microenvironment
PubMed: 38171827
DOI: 10.1111/omi.12446 -
Nutrients Dec 2023A low carbohydrate, high fat (LCHF) diet in athletes increases fat oxidation but impairs sports performance, potentially due to impaired exercise economy. Dietary...
A low carbohydrate, high fat (LCHF) diet in athletes increases fat oxidation but impairs sports performance, potentially due to impaired exercise economy. Dietary nitrate supplementation can improve exercise economy via an increase in nitric oxide production, which is initiated by the reduction of nitrate to nitrite within the oral cavity. This reaction is dependent on the presence of nitrate-reducing oral bacteria, which can potentially be altered by dietary changes, including a LCHF diet. This study explored the effect of a LCHF diet on the oral microbiome and subsequent changes to plasma nitrite concentration following nitrate supplementation. Following five days of LCHF or high carbohydrate (HCHO) control dietary intervention, highly trained male race walkers consumed 140 mL beetroot juice containing 8.4 mmol nitrate; they then provided (a) blood samples for plasma nitrate and nitrite analysis and (b) saliva samples for 16S rRNA sequencing of the oral microbiome. The LCHF diet (n = 13) reduced oral bacterial diversity and changed the relative abundance of the genera (+10%), (+3%), (-9%), and (-4%), with no significant changes observed following the HCHO diet (n = 11). Following beetroot juice ingestion, plasma nitrite concentrations were higher for the LCHF diet compared to the HCHO diet ( = 0.04). However, the absence of an interaction with the trial (pre-post) ( = 0.71) suggests that this difference was not due to the dietary intervention. In summary, we found an increase in plasma nitrate and nitrite concentrations in response to nitrate supplementation independent of diet. This suggests the oral microbiome is adaptive to dietary changes and can maintain a nitrate reduction capacity despite a decrease in bacterial diversity following the LCHF diet.
Topics: Humans; Male; Nitrites; Diet, High-Fat; Nitrates; RNA, Ribosomal, 16S; Microbiota; Bacteria; Carbohydrates; Dietary Supplements; Beta vulgaris
PubMed: 38140382
DOI: 10.3390/nu15245123 -
International Journal of Biological... Aug 2023This study intended to characterize the Gracilaria lemaneiformis (SW)-derived polysaccharide (GLP) and explore the fermentation aspects of SW and GLP by rabbitfish...
This study intended to characterize the Gracilaria lemaneiformis (SW)-derived polysaccharide (GLP) and explore the fermentation aspects of SW and GLP by rabbitfish (Siganus canaliculatus) intestinal microbes. The GLP was mainly composed of galactose and anhydrogalactose (at 2.0:0.75 molar ratio) with the linear mainstay of α-(1 → 4) linked 3,6-anhydro-α-l-galactopyranose and β-(1 → 3)-linked galactopyranose units. The in vitro fermentation results showed that the SW and GLP could reinforce the short-chain fatty (SCFAs) production and change the diversity and composition of gut microbiota. Moreover, GLP boosted the Fusobacteria and reduced the Firmicutes abundance, while SW increased the Proteobacteria abundance. Furthermore, the adequacy of feasibly harmful bacteria (such as Vibrio) declined. Interestingly, most metabolic processes were correlated with the GLP and SW groups than the control and galactooligosaccharide (GOS)-treated groups. In addition, the intestinal microbes degrade the GLP with 88.21 % of the molecular weight reduction from 1.36 × 10 g/mol (at 0 h) to 1.6 × 10 g/mol (at 24 h). Therefore, the findings suggest that the SW and GLP have prebiotic potential and could be applied as functional feed additives in aquaculture.
Topics: Gracilaria; Fermentation; Galactose; Sulfates; Gastrointestinal Microbiome; Polysaccharides; Fatty Acids, Volatile
PubMed: 37364810
DOI: 10.1016/j.ijbiomac.2023.125561 -
American Journal of Translational... 2024The prevalence of allergic rhinitis (common allergies) has increased in the last fifty years, from less than one percent to more than twenty-six percent of the...
The prevalence of allergic rhinitis (common allergies) has increased in the last fifty years, from less than one percent to more than twenty-six percent of the population. Today, more than one hundred million people in the US suffer seasonal or yearlong allergies. The hygiene hypothesis was proposed 30 years ago as a potential explanation for this phenomenon, and we built on it with the specific oral hygiene hypothesis. Our longitudinal pilot study suggested that oral probiotic deficiency is the cause of allergic rhinitis. This clinical trial served to verify our theory and evaluate the effectiveness of AllerPops for allergy relief. We carried out a phase II, randomized, double-blind, controlled, single-center 21-day study to investigate the efficacy of AllerPops to reduce nasal symptoms in 72 adult volunteers with seasonal/year-long nasal allergies and its impact on oral microbiome using amplicon sequencing of 16S ribosome RNA genes. The volunteers were randomly separated into two equally sized groups: a control group and an investigational group. Both groups were given at least three doses of AllerPops, taken every other day, and asked to answer questions about observed allergy symptoms. Volunteers in the investigational group cleaned their mouths before taking a dose and slowly dissolve the lozenge, while those in the control did not. Through this trial, we show that AllerPops prebiotic supplements are effective in providing sustained allergy relief (P = 0.002) and can modulate oral beneficial bacteria that produce short-chain fatty acids (SCFA), such as Fusobacteria, Butyrivibrio, and Peptostreptococcus. The clinical improvements correlated with changes in the relative abundance of probiotics significantly: Fusobacteria (R = 0.32, P = 0.009), Butyrivibrio (R = 0.25, P = 0.044), and Peptostreptococcus (R = 0.34, P = 0.005). These results point to the root cause of allergic rhinitis: the lack of oral probiotics that produce SCFA to pacify the immune systems. Future study of AllerPops' theory will help society redefine the best oral hygiene practice to protect oral probiotics so that we may prevent allergic and autoimmune diseases and dental/gum infections. The trial was retrospectively registered at clinicaltrials.com, with registration number NCT05956691, on 21/07/2023.
PubMed: 38322553
DOI: 10.62347/JWOU4205 -
Cell Host & Microbe Apr 2024The ubiquitous inflammophilic oral pathobiont Fusobacterium nucleatum (Fn) is widely recognized for its strong association with inflammatory dysbiotic diseases and...
The ubiquitous inflammophilic oral pathobiont Fusobacterium nucleatum (Fn) is widely recognized for its strong association with inflammatory dysbiotic diseases and cancer. Fn is subdivided into four subspecies, which are historically considered functionally interchangeable in the oral cavity. To test this assumption, we analyzed patient-matched dental plaque and odontogenic abscess clinical specimens and examined whether an inflammatory environment selects for/against particular Fn subspecies. Dental plaque harbored a greater diversity of fusobacteria, with Fn. polymorphum dominating, whereas odontogenic abscesses were exceptionally biased for the largely uncharacterized organism Fn. animalis. Comparative genomic analyses revealed significant genotypic distinctions among Fn subspecies that correlate with their preferred ecological niches and support a taxonomic reassignment of each as a distinct Fusobacterium species. Despite originating as a low-abundance organism in dental plaque, Fn. animalis typically outcompetes other oral fusobacteria within the inflammatory abscess environment, which may explain its prevalence in other oral and extraoral diseases.
Topics: Humans; Fusobacterium nucleatum; Abscess; Dental Plaque; Mouth; Fusobacterium
PubMed: 38479393
DOI: 10.1016/j.chom.2024.02.010 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2023() is an oral anaerobic bacterium that has recently been found to colonize on the surface of colorectal cancer cells in humans, and its degree of enrichment is highly... (Review)
Review
() is an oral anaerobic bacterium that has recently been found to colonize on the surface of colorectal cancer cells in humans, and its degree of enrichment is highly negatively correlated with the prognosis of tumor treatment. Numerous studies have shown that is involved in the occurrence and development of colorectal cancer (CRC), and interacts with multiple components in the tumor microenvironment to increase tumor resistance. In recent years, researchers have begun using nanomedicine to inhibit 's proliferation at the tumor site or directly target to treat CRC. This review summarizes the mechanism of in promoting CRC and the latest research progress on -related CRC therapy using different nanomaterials. Finally, the applications perspective of nanomaterials in -promoted CRC therapy was prospected.
Topics: Humans; Colorectal Neoplasms; Fusobacterium nucleatum; Base Composition; RNA, Ribosomal, 16S; Phylogeny; Sequence Analysis, DNA; Tumor Microenvironment
PubMed: 37805845
DOI: 10.13345/j.cjb.220811