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Frontiers in Cellular and Infection... 2023Over the last few decades, a growing body of evidence has suggested a role for various infectious agents in Alzheimer's disease (AD) pathogenesis. Despite diverse...
BACKGROUND
Over the last few decades, a growing body of evidence has suggested a role for various infectious agents in Alzheimer's disease (AD) pathogenesis. Despite diverse pathogens (virus, bacteria, fungi) being detected in AD subjects' brains, research has focused on individual pathogens and only a few studies investigated the hypothesis of a bacterial brain microbiome. We profiled the bacterial communities present in non-demented controls and AD subjects' brains.
RESULTS
We obtained postmortem samples from the brains of 32 individual subjects, comprising 16 AD and 16 control age-matched subjects with a total of 130 samples from the frontal and temporal lobes and the entorhinal cortex. We used full-length 16S rRNA gene amplification with Pacific Biosciences sequencing technology to identify bacteria. We detected bacteria in the brains of both cohorts with the principal bacteria comprising (formerly ) and two species each of and genera. We used a hierarchical Bayesian method to detect differences in relative abundance among AD and control groups. Because of large abundance variances, we also employed a new analysis approach based on the Latent Dirichlet Allocation algorithm, used in computational linguistics. This allowed us to identify five sample classes, each revealing a different microbiota. Assuming that samples represented infections that began at different times, we ordered these classes in time, finding that the last class exclusively explained the existence or non-existence of AD.
CONCLUSIONS
The AD-related pathogenicity of the brain microbiome seems to be based on a complex polymicrobial dynamic. The time ordering revealed a rise and fall of the abundance of with pathogenicity occurring for an off-peak abundance level in association with at least one other bacterium from a set of genera that included , , , , and . may also be involved with outcompeting the species, which were strongly associated with non-demented brain microbiota, whose early destruction could be the first stage of disease. Our results are also consistent with a leaky blood-brain barrier or lymphatic network that allows bacteria, viruses, fungi, or other pathogens to enter the brain.
Topics: Humans; Alzheimer Disease; RNA, Ribosomal, 16S; Bayes Theorem; Microbiota; Bacteria; Propionibacterium acnes; Brain; Acne Vulgaris
PubMed: 37780846
DOI: 10.3389/fcimb.2023.1123228 -
Scientific Reports Sep 2023The bacteriophage CAP 10-3 forming plaques against Cutibacterium acnes which causes skin acne was previously isolated from human skin acne lesion. Incomplete whole...
The bacteriophage CAP 10-3 forming plaques against Cutibacterium acnes which causes skin acne was previously isolated from human skin acne lesion. Incomplete whole genome sequence (WGS) of the bacteriophage CAP 10-3 was obtained and it had 29,643 bp long nucleotide with 53.86% GC content. The sequence was similar to C. acnes phage PAP 1-1 with a nucleotide sequence identity of 89.63% and the bacteriophage belonged to Pahexavirus. Bioinformatic analysis of the WGS predicted 147 ORFs and functions of 40 CDSs were identified. The predicted endolysin gene of bacteriophage CAP 10-3 was 858 bp long which was deduced as 285 amino acids (~ 31 kDa). The protein had the highest similarity with amino acid sequence of the endolysin from Propionibacterium phage PHL071N05 with 97.20% identity. The CAP 10-3 endolysin gene was amplified by PCR with primer pairs based on the gene sequence, cloned into an expression vector pET-15b and transformed into Escherichia coli BL21(DE3) strain. The predicted protein band (~ 33 kDa) for the recombinant endolysin was detected in an SDS-PAGE gel and western blot assay. The concentrated supernatant of cell lysate from E. coli BL21(DE3) (pET-15b_CAP10-3 end) and a partially purified recombinant CAP 10-3 endolysin showed antibacterial activity against C. acnes KCTC 3314 in a dose-dependent manner. In conclusion, the recombinant CAP 10-3 endolysin was successfully produced in E. coli strain and it can be considered as a therapeutic agent candidate for treatment of human skin acne.
Topics: Humans; Bacteriophages; Escherichia coli; Endopeptidases; Acne Vulgaris
PubMed: 37777575
DOI: 10.1038/s41598-023-43559-z -
GeroScience Apr 2024Oral health plays a significant role in the quality of life and overall well-being of the aging population. However, age-related changes in oral health are not well...
Oral health plays a significant role in the quality of life and overall well-being of the aging population. However, age-related changes in oral health are not well understood due to challenges with current animal models. In this study, we analyzed the oral health and microbiota of a short-lived non-human primate (i.e., marmoset), as a step towards establishing a surrogate for studying the changes that occur in oral health during human aging. We investigated the oral health of marmosets using cadaveric tissues in three different cohorts: young (aged ≤6 years), middle-aged, and older (>10 years) and assessed the gingival bacterial community using analyses of the V3-V4 variable region of 16S rRNA gene. The oldest cohort had a significantly higher number of dental caries, increased dental attrition/erosion, and deeper periodontal pocket depth scores. Oral microbiome analyses showed that older marmosets had a significantly greater abundance of Escherichia-Shigella and Propionibacterium, and a lower abundance of Agrobacterium/Rhizobium at the genus level. Alpha diversity of the microbiome between the three groups showed no significant differences; however, principal coordinate analysis and non-metric multidimensional scaling analysis revealed that samples from middle-aged and older marmosets were more closely clustered than the youngest cohort. In addition, linear discriminant analysis effect size (LEFSe) identified a higher abundance of Esherichia-Shigella as a potential pathogenic biomarker in older animals. Our findings confirm that changes in the oral microbiome are associated with a decline in oral health in aging marmosets. The current study suggests that the marmoset model recapitulates some of the changes in oral health associated with human aging and may provide opportunities for developing new preventive strategies or interventions which target these disease conditions.
Topics: Humans; Animals; Aged; Middle Aged; Callithrix; Oral Health; RNA, Ribosomal, 16S; Dental Caries; Quality of Life; Aging
PubMed: 37775702
DOI: 10.1007/s11357-023-00939-7 -
International Journal of Molecular... Sep 2023Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are...
Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are limited. There is growing evidence that complex interactions between the ocular surface microbiome (OSM) and tear fluid constituents, potentially leading to inflammatory processes, are associated with ocular surface diseases such as DED. In this study, we aimed to find unique compositional and functional features of the OSM associated with human and microbial tear proteins in patients with DED. Applying whole-metagenome shotgun sequencing of forty lid and conjunctival swabs, we identified 229 taxa, with Actinobacteria and Proteobacteria being the most abundant phyla and Propionibacterium acnes the dominating species in the cohort. When DED patients were compared to controls, the species Corynebacterium tuberculostearicum was more abundant in conjunctival samples, whereas the family Propionibacteriaceae was more abundant in lid samples. Functional analysis showed that genes of L-lysine biosynthesis, tetrapyrrole biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis, and the super pathway of L-threonine biosynthesis were enriched in conjunctival samples of controls. The relative abundances of Acinetobacter johnsonii correlated with seven human tear proteins, including mucin-16. The three most abundant microbial tear proteins were the chaperone protein DnaK, the arsenical resistance protein ArsH, and helicase. Compositional and functional features of the OSM and the tear proteome are altered in patients with DED. Ultimately, this may help to design novel interventional therapeutics to target DED.
Topics: Humans; Proteome; Eye; Dry Eye Syndromes; Face; Microbiota
PubMed: 37762390
DOI: 10.3390/ijms241814091 -
Foods (Basel, Switzerland) Sep 2023Peanuts contain nutritionally relevant levels of protein, yet are poorly digestible. Fermentation is a promising technique to boost legume protein quality, but its...
Peanuts contain nutritionally relevant levels of protein, yet are poorly digestible. Fermentation is a promising technique to boost legume protein quality, but its effect on the protein quality of raw peanuts has not been investigated. This study aimed to assess the impact of fermentation on the in vitro protein digestibility and free amino acid profile of cooked peanut slurry (peanut to water ratio 1:1). Cultures used were subsp. and a commercial fresh cheese culture that contained subsp. , , , and , fermenting at 38 °C for 48 h. Samples fermented with the combination of cultures showed higher protein digestibility, as well as softer texture. Significant increases were observed only in the sample fermented with the fresh cheese culture. While the fresh cheese culture improved the free amino acid profile after fermentation, the combination of the cultures decreased all free amino acid concentrations except for glutamine, alanine, and proline. The observed increases in in vitro protein digestibility and the free amino acid profile may be attributed to the proteolytic activities of the cultures.
PubMed: 37761158
DOI: 10.3390/foods12183447 -
Marine Drugs Aug 2023The protein extract of hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase...
The protein extract of hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory, and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of hydrolysate from cation-exchange chromatography displayed significantly high TAC, collagenase inhibitory, and antibacterial effects against , and only the Q3 fraction from anion-exchange chromatography displayed high multi-functional activities. Eight of 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results for screening with molecular docking on target proteins and were then synthesized. Thr-Gly-Thr-Trp (TGTW) displayed ABTS [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. The effect of TAC as Trolox equivalence was dependent on the concentration of TGTW. Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) exhibited collagenase inhibitory activity, which increased according to the increase in concentration, and their IC values were 0.95 mM and 0.84 mM, respectively. Peptides RDRF and His-Ala-Val-Tyr (HAVY) displayed anti- effects, with IC values of 8.57 mM and 13.23 mM, respectively. These results suggest that the hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.
PubMed: 37755082
DOI: 10.3390/md21090469 -
Scientific Reports Sep 2023Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that forms the human skin microbiota. Specific phylotypes of C. acnes have been associated with the...
Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that forms the human skin microbiota. Specific phylotypes of C. acnes have been associated with the development of acne vulgaris, while other phylotypes have been linked to healthy skin. In this scenario, bacterial extracellular vesicles (EVs) play a role in the interkingdom communication role with the human host. The purpose of this study was to examine the impact of EVs generated by various phylotypes of C. acnes on inflammation and sebum production using different in vitro skin cell types. The main findings of this study reveal that the proteomic profile of the cargo embodied in the EVs reflects distinct characteristics of the different C. acnes phylotypes in terms of life cycle, survival, and virulence. The in vitro skin cell types showed an extended pro-inflammatory modulation of SLST A1 EVs consistently triggering the activation of the inflammation-related factors IL-8, IL-6, TNFα and GM-CSF, in comparison to SLST H1 and SLST H2. Additionally, an acne-prone skin model utilizing PCi-SEB and arachidonic acid as a sebum inducer, was employed to investigate the impact of C. acnes EVs on sebum regulation. Our findings indicated that all three types of EVs significantly inhibited sebum production after a 24-h treatment period, with SLST H1 EVs exhibiting the most pronounced inhibitory effect when compared to the positive control. The results of this study highlight the protective nature of C. acnes SLST H1 EVs and their potential use as a natural treatment option for alleviating symptoms associated with inflammation and oily skin.
Topics: Humans; Proteomics; Skin; Skin Diseases; Extracellular Vesicles; Acne Vulgaris; Propionibacterium acnes; Factor VIII; Inflammation
PubMed: 37749255
DOI: 10.1038/s41598-023-43354-w -
International Orthopaedics Feb 2024Bone and joint infections are an important and increasing problem. Whether intraoperatively detected bacteria should be considered relevant or not is often difficult to...
PURPOSE
Bone and joint infections are an important and increasing problem. Whether intraoperatively detected bacteria should be considered relevant or not is often difficult to assess. This retrospective cohort study analyzes the relevance of C. acnes cultured from deep intraoperative specimens.
METHODS
All deep tissue samples collected intraoperatively between 2015 and 2020 from a quartiary care provider were evaluated for detection of C. acnes and its therapeutical consequences. Infection rates were determined according to a standardized definition and protocol and analyzed in dependence of patient's demographic data (age and gender), operative parameters (type of surgery, body region/location of surgery, and impression of the surgeon), and initiated therapy.
RESULTS
In 270 cases of more than 8500 samples, C. acnes was detected. In 30%, the detection was considered an infection. The number of samples taken and tested positive for C. acnes correlated significantly with its classification as a cause of infection. If more than one sample of the patient was positive, the detection was significantly more likely to be treated as infection (p < 0.001). In 76% of cases, a consultation to the infectious diseases (ID) department took place regarding the classification of the pathogen detection and the therapy to be carried out. Almost all of the tested isolates demonstrated the wild-type susceptibility for penicillin and clindamycin.
CONCLUSION
Intraoperative detection of skin-colonizing bacteria such as C. acnes is not always synonymous with infection. In particular, if other examination results contradict an infection (pathological sample without evidence of an infectious event, detection of malignant cells, etc.), the situation must be considered in a very differentiated manner. Interdisciplinary boards, for example, are suitable for this purpose. Care should be taken to obtain a sufficiently large number of tissue samples for microbiological examination to be able to better classify the result.
Topics: Humans; Retrospective Studies; Propionibacterium acnes; Orthopedic Procedures; Arthritis, Infectious; Skin; Gram-Positive Bacterial Infections; Shoulder Joint
PubMed: 37730929
DOI: 10.1007/s00264-023-05981-w -
Scientific Reports Sep 2023Osteoclasts degrade bone and osteoclast differentiation has been implicated in bone destruction in rheumatoid arthritis. The dairy bacterium Propionibacterium...
Surface proteins of Propionibacterium freudenreichii MJ2 inhibit RANKL-induced osteoclast differentiation by lipocalin-2 upregulation and lipocalin-2-mediated NFATc1 inhibition.
Osteoclasts degrade bone and osteoclast differentiation has been implicated in bone destruction in rheumatoid arthritis. The dairy bacterium Propionibacterium freudenreichii MJ2 (MJ2) isolated from raw milk inhibits osteoclast differentiation and ameliorates collagen-induced arthritis. This study aimed to investigate the inhibitory effect of the surface proteins of MJ2 on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and explain the underlying mechanism. The murine macrophage cell line RAW 264.7 was used to study the inhibition of osteoclast differentiation. The surface proteins significantly inhibited RANKL-induced osteoclast differentiation in a protein concentration-dependent manner by inhibiting the expression of genes and proteins related to osteoclast differentiation. RNA microarray analysis showed that the surface proteins significantly upregulated lipocalin-2 (lcn2) expression. In addition, they downregulated c-fos and NFATc1 and inhibited the expression of NFATc1-downstream genes Atp6v0d2, Calcr, and Ctsk. siRNA silencing of lcn2 decreased the extent of surface protein inhibition on osteoclast differentiation, suggesting that lcn2 plays an important role in the inhibition of RANKL-induced osteoclast differentiation. In conclusion, surface proteins of MJ2 show inhibitory effects on RANKL-induced osteoclast differentiation by upregulating lcn2 expression, in turn downregulating NFATc1, leading to the inhibition of NFATc1-downstream osteoclastogenesis-related gene expression.
Topics: Animals; Mice; Up-Regulation; Membrane Proteins; Osteoclasts; Propionibacterium freudenreichii; Lipocalin-2; RANK Ligand; Proto-Oncogene Proteins c-fos; Cell Differentiation
PubMed: 37730858
DOI: 10.1038/s41598-023-42944-y -
Cureus Aug 2023Propionibacterium acnes (P. acnes) is a slow-growing, anaerobic, gram-positive bacillus that commonly colonizes the skin and is a rare cause of CNS infections. It was...
Peculiar Case of Brain Abscess Caused by Propionibacterium acnes in an Immunocompetent Individual Without Prior Neurosurgical Intervention: A Case Report and Literature Review.
Propionibacterium acnes (P. acnes) is a slow-growing, anaerobic, gram-positive bacillus that commonly colonizes the skin and is a rare cause of CNS infections. It was previously viewed as a culture contaminant but is now recognized to infrequently cause indolent cases of CNS infections. It is even more rarely associated with abscesses in patients without a prior history of neurosurgical intervention. Due to being a slow-growing bacteria, P. acnes is frequently discovered to be the causative organism after 16S rRNA sequencing. In this case, the culture was positive. There are only five other reported cases of patients with a P. acnes abscess without prior neurosurgical intervention. Here we present the sixth case of an immunocompetent young male who was found to have a P. acnes brain abscess.
PubMed: 37724199
DOI: 10.7759/cureus.43647