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Journal of Cancer Research and Clinical... Apr 2024Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC)....
PURPOSE
Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects.
METHODS
In this study, a murine xenograft model of OSCC was established, and the mice were injected intratumorally with PBS (control group), P. intermedia (P.i group), or P. intermedia combined with an antibiotic cocktail administration (P.i + ABX group), respectively. The effects of P. intermedia and ABX administration on xenograft tumor growth, invasion, angiogenesis, and metastasis were investigated by tumor volume measurement and histopathological examination. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the changes in serum cytokine levels. Immunohistochemistry (IHC) was adopted to analyze the alterations in the levels of inflammatory cytokines and infiltrated immune cells in OSCC tissues of xenograft tumors. Transcriptome sequencing and analysis were conducted to determine differential expression genes among various groups.
RESULTS
Compared with the control treatment, P. intermedia treatment significantly promoted tumor growth, invasion, angiogenesis, and metastasis, markedly affected the levels of inflammatory cytokines, and markedly altered M2 macrophages and regulatory T cells (Tregs) infiltration in the tumor microenvironment. However, ABX administration clearly abolished these effects of P. intermedia. Transcriptome and immunohistochemical analyses revealed that P. intermedia infection increased the expression of interferon-stimulated gene 15 (ISG15). Correlation analysis indicated that the expression level of ISG15 was positively correlated with the Ki67 expression level, microvessel density, serum concentrations and tissue expression levels of inflammatory cytokines, and quantities of infiltrated M2 macrophages and Tregs. However, it is negatively correlated with the quantities of infiltrated CD4 and CD8 T cells.
CONCLUSION
In conclusion, intratumoral P. intermedia infection aggravated OSCC progression, which may be achieved through upregulation of ISG15. This study sheds new light on the possible pathogenic mechanism of intratumoral P. intermedia in OSCC progression, which could be a prospective target for OSCC prevention and treatment.
Topics: Animals; Mice; Cytokines; Humans; Mouth Neoplasms; Ubiquitins; Disease Progression; Up-Regulation; Prevotella intermedia; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays; Mice, Nude; Bacteroidaceae Infections; Cell Line, Tumor; Mice, Inbred BALB C; Carcinoma, Squamous Cell; Anti-Bacterial Agents
PubMed: 38644421
DOI: 10.1007/s00432-024-05730-5 -
Animal Microbiome Apr 2024Post weaning diarrhoea (PWD) causes piglet morbidity and mortality at weaning and is a major driver for antimicrobial use worldwide. New regulations in the EU limit the...
BACKGROUND
Post weaning diarrhoea (PWD) causes piglet morbidity and mortality at weaning and is a major driver for antimicrobial use worldwide. New regulations in the EU limit the use of in-feed antibiotics (Ab) and therapeutic zinc oxide (ZnO) to prevent PWD. New approaches to control PWD are needed, and understanding the role of the microbiota in this context is key. In this study, shotgun metagenome sequencing was used to describe the taxonomic and functional evolution of the faecal microbiota of the piglet during the first two weeks post weaning within three experimental groups, Ab, ZnO and no medication, on commercial farms using antimicrobials regularly in the post weaning period.
RESULTS
Diversity was affected by day post weaning (dpw), treatment used and diarrhoea but not by the farm. Microbiota composition evolved towards the dominance of groups of species such as Prevotella spp. at day 14dpw. ZnO inhibited E. coli overgrowth, promoted higher abundance of the family Bacteroidaceae and decreased Megasphaera spp. Animals treated with Ab exhibited inconsistent taxonomic changes across time points, with an overall increase of Limosilactobacillus reuteri and Megasphaera elsdenii. Samples from non-medicated pigs showed virulence-related functions at 7dpw, and specific ETEC-related virulence factors were detected in all samples presenting diarrhoea. Differential microbiota functions of pigs treated with ZnO were related to sulphur and DNA metabolism, as well as mechanisms of antimicrobial and heavy metal resistance, whereas Ab treated animals exhibited functions related to antimicrobial resistance and virulence.
CONCLUSION
Ab and particularly ZnO maintained a stable microbiota composition and functionality during the two weeks post weaning, by limiting E. coli overgrowth, and ultimately preventing microbiota dysbiosis. Future approaches to support piglet health should be able to reproduce this stable gut microbiota transition during the post weaning period, in order to maintain optimal gut physiological and productive conditions.
PubMed: 38627869
DOI: 10.1186/s42523-024-00306-7 -
BMJ Open Apr 2024To make a descriptive comparison of antibodies to four major periodontal bacteria and their relation to the respiratory diseases asthma and bronchitis/emphysema, and to...
OBJECTIVES
To make a descriptive comparison of antibodies to four major periodontal bacteria and their relation to the respiratory diseases asthma and bronchitis/emphysema, and to cancer incidence.
METHODS
The serum of a random sample of men with no history of cancer incidence (n=621) was analysed by the ELISA method for antibody levels of four periodontal bacteria; the anaerobes of the so-called red complex (TF), (PG), and (TD), and the facultative anaerobe (AA). The antibody readings were divided into quartiles and the distribution of cases of the relevant diseases as compared with the non-cases. Comparisons of the quartile distributions were by the Pearson χ test. Data and serum from the Oslo II study of Norwegian men from 2000 were used. The ELISA analyses were performed on thawed frozen serum. Cancer data from 17.5 years of follow-up were provided by the Norwegian Cancer Registry.
RESULTS
In all, 52 men had reported asthma and 23 men had bronchitis/emphysema at the health screening. Results on cancer incidence are given for all respiratory cancers, n=23, and bronchi and lung cancers separately, n=18. Stratified analyses were performed for the four endpoints showing significant association with low levels of TD antibodies for bronchitis; p=0.035. Both TF and TD were significant for low levels of antibodies among daily smokers; p=0.030 for TF and p<0.001 for TD in the analysis of the full study sample. For PG and AA, no such associations were observed. An association with respiratory cancers was not observed.
CONCLUSION
A low level of TD was associated with bronchitis/emphysema compared with the rest of the cohort. In the total study sample, low levels of antibodies to both TF and TD were associated with daily smoking.
Topics: Male; Humans; Cohort Studies; Porphyromonas gingivalis; Antibodies; Neoplasms; Respiratory Tract Diseases; Asthma; Bronchitis; Emphysema
PubMed: 38626983
DOI: 10.1136/bmjopen-2023-082116 -
Gut Microbes 2024Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the...
Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between and obesity in children ( = 0.003). Next, the effect of on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of . increased serum levels of fasting blood glucose ( < 0.01), insulin ( < 0.01) and interleukin-1β (IL-1β) ( < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that reduced the relative abundance of the genus in mice ( < 0.01). Further analysis on bile acids (BAs) revealed that increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice ( < 0.05). This study demonstrated for the first time that has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of genus and bile acids.
Topics: Humans; Child; Animals; Mice; Insulin; Gastrointestinal Microbiome; Pediatric Obesity; Bile Acids and Salts; Blood Glucose; Diabetes Mellitus, Type 2; Mice, Obese; Diet, High-Fat; Mice, Inbred C57BL; Prevotella
PubMed: 38626129
DOI: 10.1080/19490976.2024.2340487 -
Nutrients Mar 2024The gut microbiota is a dynamic ecosystem that plays a pivotal role in maintaining host health. The perturbation of these microbes has been linked to several health...
The gut microbiota is a dynamic ecosystem that plays a pivotal role in maintaining host health. The perturbation of these microbes has been linked to several health conditions. Hence, they have emerged as promising targets for understanding and promoting good health. Despite the growing body of research on the role of sodium in health, its effects on the human gut microbiome remain under-explored. Here, using nutrition and metagenomics methods, we investigate the influence of dietary sodium intake and alterations of the human gut microbiota. We found that a high-sodium diet (HSD) altered the gut microbiota composition with a significant reduction in and inverse increase in compared to a low-sodium diet (LSD). However, there is no clear distinction in the Firmicutes/Bacteroidetes (F/B) ratio between the two diet types. Metabolic pathway reconstruction revealed the presence of sodium reabsorption genes in the HSD, but not LSD. Since it is currently difficult in microbiome studies to confidently associate the F/B ratio with what is considered healthy (e.g., low sodium) or unhealthy (e.g., high sodium), we suggest that the use of a genus-based ratio such as the / (B/P) ratio may be more beneficial for the application of microbiome studies in health.
Topics: Humans; Sodium Chloride, Dietary; Microbiota; Bacteroides; Bacteroidetes; Firmicutes; Prevotella; Sodium
PubMed: 38612976
DOI: 10.3390/nu16070942 -
The Science of the Total Environment Jun 2024Animal hosts harbor diverse assemblages of microbial symbionts that play crucial roles in the host's lifestyle. The link between microbial symbiosis and host development...
Animal hosts harbor diverse assemblages of microbial symbionts that play crucial roles in the host's lifestyle. The link between microbial symbiosis and host development remains poorly understood. In particular, little is known about the adaptive evolution of gut bacteria in host-microbe symbioses. Recently, symbiotic relationships have been categorized as open, closed, or mixed, reflecting their modes of inter-host transmission and resulting in distinct genomic features. Members of the genus Bacteroides are the most abundant human gut microbiota and possess both probiotic and pathogenic potential, providing an excellent model for studying pan-genome evolution in symbiotic systems. Here, we determined the complete genome of an novel clinical strain PL2022, which was isolated from a blood sample and performed pan-genome analyses on a representative set of Bacteroides cellulosilyticus strains to quantify the influence of the symbiotic relationship on the evolutionary dynamics. B. cellulosilyticus exhibited correlated genomic features with both open and closed symbioses, suggesting a mixed symbiosis. An open pan-genome is characterized by abundant accessory gene families, potential horizontal gene transfer (HGT), and diverse mobile genetic elements (MGEs), indicating an innovative gene pool, mainly associated with genomic islands and plasmids. However, massive parallel gene loss, weak purifying selection, and accumulation of positively selected mutations were the main drivers of genome reduction in B. cellulosilyticus. Metagenomic read recruitment analyses showed that B. cellulosilyticus members are globally distributed and active in human gut habitats, in line with predominant vertical transmission in the human gut. However, existence and/or high abundance were also detected in non-intestinal tissues, other animal hosts, and non-host environments, indicating occasional horizontal transmission to new niches, thereby creating arenas for the acquisition of novel genes. This case study of adaptive evolution under a mixed host-microbe symbiosis advances our understanding of symbiotic pan-genome evolution. Our results highlight the complexity of genetic evolution in this unusual intestinal symbiont.
Topics: Symbiosis; Gastrointestinal Microbiome; Bacteroides; Humans; Genome, Bacterial; Evolution, Molecular; Gene Transfer, Horizontal
PubMed: 38604355
DOI: 10.1016/j.scitotenv.2024.172251 -
Journal of Animal Science and... Apr 2024Optimal gut health is important to maximize growth performance and feed efficiency in broiler chickens. A total of 1,365 one-day-old male Ross 308 broiler chickens were...
BACKGROUND
Optimal gut health is important to maximize growth performance and feed efficiency in broiler chickens. A total of 1,365 one-day-old male Ross 308 broiler chickens were randomly divided into 5 treatments groups with 21 replicates, 13 birds per replicate. The present research investigated effects of microbial muramidase or a precision glycan alone or in combination on growth performance, apparent total tract digestibility, total blood carotenoid content, intestinal villus length, meat quality and gut microbiota in broiler chickens. Treatments included: NC: negative control (basal diet group); PC: positive control (basal diet + 0.02% probiotics); MR: basal diet + 0.035% microbial muramidase; PG: basal diet + 0.1% precision glycan; and MRPG: basal diet + 0.025% MR + 0.1% PG, respectively.
RESULTS
MRPG group increased the body weight gain and feed intake (P < 0.05) compared with NC group. Moreover, it significantly increased total serum carotenoid (P < 0.05) and MRPG altered the microbial diversity in ileum contents. The MRPG treatment group increased the abundance of the phylum Firmicutes, and family Lachnospiraceae, Ruminococcaceae, Oscillospiraceae, Lactobacillaceae, Peptostreptococcaceae and decreased the abundance of the phylum Campilobacterota, Bacteroidota and family Bacteroidaceae. Compared with the NC group, the chickens fed MRPG showed significantly increased in duodenum villus length at end the trial.
CONCLUSION
In this study, overall results showed that the synergetic effects of MR and PG showed enhancing growth performance, total serum carotenoid level and altering gut microbiota composition of broilers. The current research indicates that co-supplementation of MR and PG in broiler diets enhances intestinal health, consequently leading to an increased broiler production.
PubMed: 38594781
DOI: 10.1186/s40104-024-01010-x -
EBioMedicine May 2024Gut dysbiosis is present in chronic hepatitis B virus (HBV) infection. In this study, we integrated microbiome and metabolome analysis to investigate the role of gut...
BACKGROUND
Gut dysbiosis is present in chronic hepatitis B virus (HBV) infection. In this study, we integrated microbiome and metabolome analysis to investigate the role of gut microbiome in virological response to nucleos(t)ide analogues (NAs) treatment.
METHODS
Chronic HBV patients were prospectively recruited for steatosis and fibrosis assessments via liver elastography, with full-length 16S sequencing performed to identify the compositional gut microbiota differences. Fasting plasma bile acids were quantified by liquid chromatography-tandem mass spectrometry.
FINDINGS
All patients (n = 110) were characterized into three distinct microbial clusters by their dominant genus: c-Bacteroides, c-Blautia, and c-Prevotella. Patients with c-Bacteroides had a higher plasma ursodeoxycholic acids (UDCA) level and an increase in 7-alpha-hydroxysteroid dehydrogenase (secondary bile acid biotransformation) than other clusters. In NAs-treated patients (n = 84), c-Bacteroides was associated with higher odds of plasma HBV-DNA undetectability when compared with non-c-Bacteroides clusters (OR 3.49, 95% CI 1.43-8.96, p = 0.01). c-Blautia was positively associated with advanced fibrosis (OR 2.74, 95% CI 1.09-7.31, p = 0.04). No such associations were found in treatment-naïve patients. Increased Escherichia coli relative abundance (0.21% vs. 0.03%, p = 0.035) was found in on-treatment patients (median treatment duration 98.1 months) with advanced fibrosis despite HBV DNA undetectability. An enrichment in l-tryptophan biosynthesis was observed in patients with advanced fibrosis, which exhibited a positive correlation with Escherichia coli.
INTERPRETATION
Collectively, unique bacterial signatures, including c-Bacteroides and c-Blautia, were associated with virological undetectability and fibrosis evolution during NAs therapy in chronic HBV, setting up intriguing possibilities in optimizing HBV treatment.
FUNDING
This study was supported by the Guangdong Natural Science Fund (2019A1515012003).
Topics: Humans; Gastrointestinal Microbiome; Hepatitis B, Chronic; Male; Female; Middle Aged; Adult; Hepatitis B virus; Bacteroides; Antiviral Agents; Metabolome; Treatment Outcome; Liver Cirrhosis; Viral Load; Bile Acids and Salts; Metagenomics; Nucleosides
PubMed: 38583259
DOI: 10.1016/j.ebiom.2024.105101 -
Gut Pathogens Apr 2024Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne...
BACKGROUND
Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months.
CASE PRESENTATION
To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time.
CONCLUSION
This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.
PubMed: 38581020
DOI: 10.1186/s13099-024-00614-y -
Frontiers in Immunology 2024Chronic periodontitis (CP), an inflammatory disease of periodontal tissues driven by a dysbiotic subgingival bacterial biofilm, is also associated with several systemic...
Chronic periodontitis (CP), an inflammatory disease of periodontal tissues driven by a dysbiotic subgingival bacterial biofilm, is also associated with several systemic diseases, including rheumatoid arthritis (RA). , one of the bacterial species implicated in CP as a keystone pathogen produces peptidyl arginine deiminase (PPAD) that citrullinates C-terminal arginine residues in proteins and peptides. Autoimmunity to citrullinated epitopes is crucial in RA, hence PPAD activity is considered a possible mechanistic link between CP and RA. Here we determined the PPAD enzymatic activity produced by clinical isolates of , sequenced the gene, and correlated the results with clinical determinants of CP in patients from whom the bacteria were isolated. The analysis revealed variations in PPAD activity and genetic diversity of the gene in clinical isolates. Interestingly, the severity of CP was correlated with a higher level of PPAD activity that was associated with the presence of a triple mutation (G231N, E232T, N235D) in PPAD in comparison to W83 and ATCC 33277 type strains. The relation between mutations and enhanced activity was verified by directed mutagenesis which showed that all three amino acid residue substitutions must be introduced into PPAD expressed by the type strains to obtain the super-active enzyme. Cumulatively, these results may lead to the development of novel prognostic tools to assess the progress of CP in the context of associated RA by analyzing the genotype in CP patients infected with .
Topics: Humans; Protein-Arginine Deiminases; Porphyromonas gingivalis; Peptides; Periodontium; Chronic Periodontitis
PubMed: 38576615
DOI: 10.3389/fimmu.2024.1355357