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Journal of Experimental & Clinical... Jan 2022Immune checkpoint inhibitor-related cardiotoxicity is one of the most lethal adverse effects, and thus, the identification of underlying mechanisms for developing...
BACKGROUND
Immune checkpoint inhibitor-related cardiotoxicity is one of the most lethal adverse effects, and thus, the identification of underlying mechanisms for developing strategies to overcome it has clinical importance. This study aimed to investigate whether microbiota-host interactions contribute to PD-1/PD-L1 inhibitor-related cardiotoxicity.
METHODS
A mouse model of immune checkpoint inhibitor-related cardiotoxicity was constructed by PD-1/PD-L1 inhibitor BMS-1 (5 and 10 mg/kg), and cardiomyocyte apoptosis and cardiotoxicity were determined by hematoxylin and eosin, Masson's trichome and TUNEL assays. 16S rRNA sequencing was used to define the gut microbiota composition. Gut microbiota metabolites short-chain fatty acids (SCFAs) were determined by HPLC. The serum levels of myocardial enzymes (creatine kinase, aspartate transaminase, creatine kinase-MB and lactate dehydrogenase) and the production of M1 factors (TNF-α and IL-1β) were measured by ELISA. The colonic macrophage phenotype was measured by mmunofluorescence and qPCR. The expression of Claudin-1, Occludin, ZO-1 and p-p65 was measured by western blot. The gene expression of peroxisome proliferator-activated receptor α (PPARα) and cytochrome P450 (CYP) 4X1 was determined using qPCR. Statistical analyses were performed using Student's t-test for two-group comparisons, and one-way ANOVA followed by Student-Newman-Keul test for multiple-group comparisons.
RESULTS
We observed intestinal barrier injury and gut microbiota dysbiosis characterized by Prevotellaceae and Rikenellaceae genus depletion and Escherichia-Shigella and Ruminococcaceae genus enrichment, accompanied by low butyrate production and M1-like polarization of colonic macrophages in BMS-1 (5 and 10 mg/kg)-induced cardiotoxicity. Fecal microbiota transplantation mirrored the effect of BMS-1 on cardiomyocyte apoptosis and cardiotoxicity, while macrophage depletion and neutralization of TNF-α and IL-1β greatly attenuated BMS-1-induced cardiotoxicity. Importantly, Prevotella loescheii recolonization and butyrate supplementation alleviated PD-1/PD-L1 inhibitor-related cardiotoxicity. Mechanistically, gut microbiota dysbiosis promoted M1-like polarization of colonic macrophages and the production of proinflammatory factors TNF-α and IL-1β through downregulation of PPARα-CYP4X1 axis.
CONCLUSIONS
Intestinal barrier dysfunction amplifies PD-1/PD-L1 inhibitor-related cardiotoxicity by upregulating proinflammatory factors TNF-α and IL-1β in colonic macrophages via downregulation of butyrate-PPARα-CYP4X1 axis. Thus, targeting gut microbiota to polarize colonic macrophages away from the M1-like phenotype could provide a potential therapeutic strategy for PD-1/PD-L1 inhibitor-related cardiotoxicity.
Topics: Animals; Butyrates; Cardiotoxicity; Colon; Cytochrome P-450 Enzyme System; Disease Models, Animal; Fecal Microbiota Transplantation; Humans; Immune Checkpoint Inhibitors; Macrophages; Male; Mice; Transfection
PubMed: 34980222
DOI: 10.1186/s13046-021-02201-4 -
Journal of Indian Society of... 2023is a Gram-negative anaerobic bacilli. The phenotypic characteristics of the various species of are similar, which often makes it difficult in routine differentiation...
Simultaneous detection and evaluation of , and in subgingival plaque samples of chronic periodontitis and healthy individuals through multiplex polymerase chain reaction.
BACKGROUND
is a Gram-negative anaerobic bacilli. The phenotypic characteristics of the various species of are similar, which often makes it difficult in routine differentiation and identification of all the species.
AIM
The purpose of the study was to detect and compare presence of , and in subgingival plaque samples of chronic periodontitis and healthy individuals.
MATERIALS AND METHODS
Two hundred and thirty-six subjects were considered consisting of chronic periodontitis (128) and healthy (108) individuals. Subgingival plaque sample was collected in reduced transport fluid and analyzed. DNA extraction and polymerase chain reaction (PCR) were performed for genus followed by positive samples were considered for the detection of selected species through multiplex PCR using specific primers.
RESULTS
Out of 236 samples, 94.1% were positive for genus . Out of 222 cases showed the highest number of cases positive (59.5%) followed by (57.2%), (55.4%), and (40.1%). Species were analyzed individually between chronic periodontitis and healthy, , and showed greater positivity in healthy compared to chronic periodontitis. Positivity for was high in chronic periodontitis compared to healthy.
CONCLUSION
The number of positive cases for species, when correlated with clinical parameters showed an increase in mean score for all clinical parameters assessed, suggesting the presence of variation in the prevalence of species and geographic variation do exist in oral microflora. Findings suggest that they can be normal commensals and opportunistic.
PubMed: 37346862
DOI: 10.4103/jisp.jisp_154_22 -
BMC Infectious Diseases Mar 2014Anaerobes are a major component of gut flora. They play an important role in the pathogenesis of infections resulting from breaches in mucus membranes. Because of the...
BACKGROUND
Anaerobes are a major component of gut flora. They play an important role in the pathogenesis of infections resulting from breaches in mucus membranes. Because of the difficulties in cultivating and identifying it, their role continues to be undermined. The purpose of this paper is to report a case of Prevotella loescheii bacteremic skin and soft tissue infection and review the literature.
CASE PRESENTATION
A 42-year-old Caucasian man was admitted for an elective bariatric surgery. A lengthy intensive care unit stay and buttocks decubitus ulcers complicated his post-operative course. After being transferred to a long-term care facility, the decubitus ulcer became secondarily infected with multiple bacteria including P. loescheii; an anaerobe that grew in blood and wound cultures. The patient was treated successfully with aggressive surgical debridement, antibiotics and subsequent wound care.
CONCLUSION
P. loescheii colonizes the gut and plays an important role in periodontal infections. In rare occasions and under suitable circumstances, it can infect skin and soft tissues as well as joints. Given the difficulties in isolating anaerobes in the microbiology lab, considering this bacterium alongside other anaerobes in infections of devitalized tissue is indicated even if cultures were reported negative.
Topics: Adult; Anti-Bacterial Agents; Bacteroidaceae Infections; Buttocks; Humans; Male; Pressure Ulcer; Prevotella; Skin Diseases, Bacterial; Soft Tissue Infections
PubMed: 24661318
DOI: 10.1186/1471-2334-14-162 -
Veterinary Microbiology May 2017Periodontitis is a polymicrobial infectious disease that causes occlusion change, tooth loss, difficulty in rumination, and premature culling of animals. This study...
Periodontitis is a polymicrobial infectious disease that causes occlusion change, tooth loss, difficulty in rumination, and premature culling of animals. This study aimed to detect species of the genera Porphyromonas and Prevotella present in the periodontal pocket of sheep with lesions deeper than 5mm (n=14) and in the gingival sulcus of animals considered periodontally healthy (n=20). The presence of microorganisms was evaluated by polymerase chain reaction (PCR) using specific primers for Porphyromonas asaccharolytica, Porphyromonas endodontalis, Porphyromonas gingivalis, Porphyromonas gulae, Prevotella buccae, Prevotella intermedia, Prevotella loescheii, Prevotella melaninogenica, Prevotella nigrescens, Prevotella oralis, and Prevotella tannerae. Prevalence and risk analysis were performed using Student's t-test and Spearman's correlation. Among the Prevotella and Porphyromonas species detected in the periodontal lesions of sheep, P. melaninogenica (85.7%), P. buccae (64.3%), P. gingivalis (50%), and P. endodontalis (50%) were most prevalent. P. gingivalis (15%) and P. oralis (10%) prevailed in the gingival sulcus. P. gulae and P. tannerae were not detected in the 34 samples studied. Data evaluation by t-test verified that occurrence of P. asaccharolytica, P. endodontalis, P. gingivalis, P. buccae, P. intermedia, P. melalinogenica, and P. nigrescens correlated with sheep periodontitis. The findings of this study will be an important contribution to research on pathogenesis of sheep periodontitis and development of its control measures.
Topics: Animals; Bacteria, Anaerobic; Biofilms; Periodontal Pocket; Periodontitis; Polymerase Chain Reaction; Porphyromonas; Prevotella; Sheep; Sheep Diseases
PubMed: 28619155
DOI: 10.1016/j.vetmic.2017.03.032 -
Frontiers in Oral Health 2021Periodontitis, a chronic inflammatory oral infection is the outcome of disturbances in the homeostasis of the oral biofilm microbiota. A number of studies have found...
Periodontitis, a chronic inflammatory oral infection is the outcome of disturbances in the homeostasis of the oral biofilm microbiota. A number of studies have found the occurrence of species in elevated levels in periodontitis compared to healthy subjects. Even though different aspects of as part of oral biofilm have been studied, biofilms formed by these species have not been characterized systematically. The objective of this study was to characterize biofilms formed by several species and further to assess biofilm inhibition and detachment of preformed biofilms. Biofilms were grown in 24-well plates containing brucella broth in anaerobic conditions for 3 days, and were quantified using crystal violet staining. Images of SYTO 9 Green fluorescent stained biofilms were captured using confocal microscopy. Biofilm inhibition and detachment by proteinase and DNase I was tested. The biochemical characterization included quantification of proteins and DNA in the biofilms and biofilm-supernatants. and showed highest biofilm formation. formed significantly higher amounts of biofilms than ( = 0.005) and ( = 0.0013). Inhibition of biofilm formation was significant only in the case of when treated with proteinase ( = 0.037), whereas with DNase I treatment, the inhibition was not significant ( = 0.531). Overall, proteinase was more effective in biofilm detachment than DNase I. Protein and DNA content were higher in biofilm than the supernatant with the highest amounts found in biofilm and supernatants. biofilms appeared to secrete large amounts of proteins extracellularly into the biofilm-supernatants. Significant differences among species to form biofilms may imply their variable abilities to get integrated into oral biofilm communities. Of the species that were able to grow as biofilms, DNase I and proteinase inhibited the biofilm growth or were able to cause biofilm detachment.
PubMed: 35048047
DOI: 10.3389/froh.2021.724194 -
Journal of Bacteriology Apr 1994The 2.4-kb plaA gene, which encodes a Prevotella loescheii galactoside-specific adhesin, contains a programmed frameshifting hop. The frameshift region consists of two...
The 2.4-kb plaA gene, which encodes a Prevotella loescheii galactoside-specific adhesin, contains a programmed frameshifting hop. The frameshift region consists of two UAA termination codons, two repeats of four identical bases between the terminators, and a stem-loop structure that has the potential to form a pseudoknot located downstream from the second UAA. The stem-loop and pseudoknot are features found in a number of retroviruses where frameshifting is a more common occurrence. The terminators, sequence repeats, and secondary structures were identified in both the P. loescheii plaA gene and the mRNA transcript. An in-frame fusion of the entire plaA frameshift region between codons 9 and 10 of the lacZ gene permitted relatively efficient expression (4 to 25% of that of the control) of beta-galactosidase in Escherichia coli.
Topics: Adhesins, Bacterial; Amino Acid Sequence; Bacteria; Bacterial Adhesion; Bacterial Proteins; Base Sequence; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genes, Reporter; Lac Operon; Lectins; Models, Genetic; Molecular Sequence Data; Nucleic Acid Conformation; Reading Frames; Recombinant Fusion Proteins
PubMed: 8144461
DOI: 10.1128/jb.176.7.1944-1948.1994 -
Ear, Nose, & Throat Journal Sep 2023Paragangliomas are rare, slow-growing, hypervascular, catecholamine-secreting neuroendocrine tumors arising from the paraganglia. Paragangliomas are rarely found in the...
Paragangliomas are rare, slow-growing, hypervascular, catecholamine-secreting neuroendocrine tumors arising from the paraganglia. Paragangliomas are rarely found in the head and neck and are typically benign, presenting as a painless, slow-growing mass. Surgical extirpation in combination with long-term surveillance has been long regarded as the standard of care; however, the advances in imaging, radiation therapy, and embolization techniques have improved diagnostic and therapeutic modalities. We present a case of an 87-year-old female who had previously undergone resection of a paraganglioma in 1998, with no evidence of disease in 2002. Eighteen years later, the patient presented to the clinic with otogenic complaints. Imaging showed an expansive mass from the jugular foramen with bone destruction and opacification within the ear canal. The patient opted for observation. The patient eventually presented to the emergency room with neurologic manifestations. Imaging showed a cerebellar abscess prompting emergency drainage. Intraoperative cultures grew and , and the patient was started on 6 weeks of IV antibiotic therapy. Debulking of the paraganglioma was performed followed several months by mastoid and ear canal obliteration; however, the patient experienced complications, including dehiscence of the external auditory canal and infection. The patient was eventually treated successfully, marked by a reduction in complaints, a return to baseline activities, and imaging showing no increase in tumor size.
Topics: Female; Humans; Aged, 80 and over; Paraganglioma; Diagnostic Imaging; Head and Neck Neoplasms; Neck; Mastoid
PubMed: 37551648
DOI: 10.1177/01455613231187762 -
Clinical and Diagnostic Laboratory... Jul 1997Oral Prevotella and Capnocytophaga species, regularly isolated from periodontal pockets and associated with extraoral infections, secret specific immunoglobulin A1...
Oral Prevotella and Capnocytophaga species, regularly isolated from periodontal pockets and associated with extraoral infections, secret specific immunoglobulin A1 (IgA1) proteases cleaving human IgA1 in the hinge region into intact Fab and Fc fragments. To investigate whether these enzymes are subject to inhibition in vivo in humans, we tested 34 sera from periodontally diseased and healthy individuals in an enzyme-linked immunosorbent assay for the presence and titers of inhibition of seven Prevotella and Capnocytophaga proteases. All or nearly all of the sera inhibited the IgA1 protease activity of Prevotella buccae, Prevotella oris, and Prevotella loescheii. A minor proportion of the sera inhibited Prevotella buccalis, Prevotella denticola, and Prevotella melaninogenica IgA1 proteases, while no sera inhibited Capnocytophaga ochracea IgA1 protease. All inhibition titers were low, ranging from 5 to 55, with titer being defined as the reciprocal of the dilution of serum causing 50% inhibition of one defined unit of protease activity. No correlation between periodontal disease status and the presence, absence, or titer of inhibition was observed. The nature of the low titers of inhibition in all sera of the IgA1 proteases of P. buccae, P. oris, and P. loescheii was further examined. In size exclusion chromatography, inhibitory activity corresponded to the peak volume of IgA. Additional inhibition of the P. oris IgA1 protease was found in fractions containing both IgA and IgG. Purification of the IgG fractions of five sera by passage of the sera on a protein G column resulted in recovery of inhibitory IgG antibodies against all three IgA1 proteases, with the highest titer being for the P. oris enzyme. These finding indicate that inhibitory activity is associated with enzyme-neutralizing antibodies.
Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Binding, Competitive; Capnocytophaga; Humans; Immunoglobulin A; Immunoglobulin G; Middle Aged; Periodontal Diseases; Prevotella; Serine Endopeptidases; Serine Proteinase Inhibitors
PubMed: 9220164
DOI: 10.1128/cdli.4.4.458-464.1997 -
BioMed Research International 2022The characteristics of the oral microbiota may depend on oral health, age, diet, and geography, but the influence of the geographic setting on the oral microbiota has...
The characteristics of the oral microbiota may depend on oral health, age, diet, and geography, but the influence of the geographic setting on the oral microbiota has received limited attention. The characteristics of oral microbiota have been reported to differ between urban and rural environments. In order to minimize the influence of genetic background, we recruited 54 volunteers from the same ethnic group, living in urban and rural areas of Gansu Province, China. We collected dental plaque samples and divided them into four groups according to the participant's area of residence and dental caries status. We sequenced the 16S rRNA of these samples using the Pacific Biosciences sequencing platform and analyzed the correlation between the geographic area and the characteristics of the oral microbiota. Analysis of the alpha and beta diversity revealed that there were significant differences in diversity and composition of dental plaque microflora among the four groups. Cluster analysis revealed that geographic area played an important role in determining the oral microbiota. Network analysis of oral microorganisms showed that geographic differences had major influence on the composition characteristics and internal structure of oral microorganisms. We found that some dominant strains which may play a key role in maintaining oral health, such as , and , were less affected by the geographic setting. These results provide a deeper understanding of factors influencing the composition of the oral microbiota and could contribute to early diagnosis and effective prevention of dental caries in different settings.
Topics: Dental Caries; Dental Plaque; Ethnicity; Humans; Microbiota; RNA, Ribosomal, 16S
PubMed: 35800217
DOI: 10.1155/2022/6544497 -
Journal of Bacteriology Nov 1992We cloned and sequenced the Prevotella loescheii gene plaA, which encodes a lectin-like adhesin that mediates the coaggregation of P. loescheii 1295 with Streptococcus... (Comparative Study)
Comparative Study
We cloned and sequenced the Prevotella loescheii gene plaA, which encodes a lectin-like adhesin that mediates the coaggregation of P. loescheii 1295 with Streptococcus oralis 34. A probe derived from the N-terminal amino acid sequence of the purified adhesin was used to identify the plaA gene from a P. loescheii genomic library constructed in lambda GEM-11. Sequence analysis of plaA indicates that the initial translation product contains a 22-amino-acid leader. The reading frame of the plaA gene is interrupted after amino acid 28 of the mature protein by a TAA termination codon. Amplification of the P. loescheii genomic DNA in the region surrounding this codon by the polymerase chain reaction followed by DNA sequencing of the cloned DNA fragment established that this stop codon was not an experimental artifact. A frameshift beginning 29 bp downstream of the ochre terminator was required to access the only large open reading frame in the gene. Amino acid sequences of six purified peptides derived by limited proteolysis of adhesin with endoproteinase Lys-C matched the downstream amino acid sequence derived by translation of the large open reading frame. The gene coding sequence of 2.4 kb contains sufficient information for the synthesis of an 89-kDa protein. A putative rho-independent terminator (delta G = -25.5 kcal/mol [ca. -107 kJ/mol]) was detected 38 bp downstream from the plaA stop codon.
Topics: Adhesins, Bacterial; Amino Acid Sequence; Bacterial Adhesion; Bacterial Proteins; Bacteroides; Base Sequence; Blotting, Southern; Calorimetry; Cloning, Molecular; Codon; DNA, Bacterial; Escherichia coli; Frameshift Mutation; Genes, Bacterial; Genomic Library; Lectins; Molecular Sequence Data; Molecular Weight; Oligonucleotide Probes; Open Reading Frames; Plasmids; Protein Conformation; Restriction Mapping; Sequence Homology, Amino Acid; Terminator Regions, Genetic
PubMed: 1429455
DOI: 10.1128/jb.174.22.7328-7336.1992