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Nature Communications Dec 2023Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated...
Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.
Topics: Humans; Female; Animals; Mice; Hyaluronoglucosaminidase; Skin; Acne Vulgaris; Propionibacterium acnes; Amino Acids
PubMed: 38052825
DOI: 10.1038/s41467-023-43833-8 -
Frontiers in Endocrinology 2023The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations,...
INTRODUCTION
The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer.
METHODS
We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer.
RESULTS
Our analysis reveals a significant prevalence of in 58.6% thyroid cancer samples compared to other cancer types (). Immune cell fraction analysis between thyroid cancer samples with high and low loads identify enrichment of immunosuppressive cells, including Tregs (), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression is associated with the infection. A higher burden of was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer.
CONCLUSION
is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.
Topics: Humans; Propionibacterium acnes; Anti-Bacterial Agents; Base Sequence; Thyroid Neoplasms; Tumor Microenvironment
PubMed: 38027096
DOI: 10.3389/fendo.2023.1152514 -
Molecules (Basel, Switzerland) Nov 2023Dry rose extract (DRE) obtained industrially by aqueous ethanol extraction from flowers and its phenolic-enriched fraction, obtained by re-extraction with ethyl acetate...
Dry rose extract (DRE) obtained industrially by aqueous ethanol extraction from flowers and its phenolic-enriched fraction, obtained by re-extraction with ethyl acetate (EAE) were the subject of this study. H NMR of DRE allowed the identification and quantitation of fructose and glucose, while the combined use of HPLC-DAD-ESIMS and HPLC-HRMS showed the presence of 14 kaempferol glycosides, 12 quercetin glycosides, 4 phenolic acids and their esters, 4 galloyl glycosides, 7 ellagitannins, and quinic acid. In addition, the structures of 13 of the flavonoid glycosides were further confirmed by NMR. EAE was found to be richer in TPC and TFC and showed better antioxidant activity (DPPH, ABTS, and FRAP) compared to DRE. Both extracts displayed significant activity against , , and , but showed no activity against Toxicity tests on normal human skin fibroblasts revealed low toxicity for both extracts with stronger effects observed at 24 hours of treatment that were compensated for over the following two days. Human hepatocarcinoma (HepG2) cells exhibited an opposite response after treatment with a concentration above 350 µg/mL for EAE and 500 µg/mL for DRE, showing increased toxicity after the third day of treatment. Lower concentrations were non-toxic and did not significantly affect the cell cycle parameters of either of the cell lines.
Topics: Humans; Antioxidants; Rosa; Plant Extracts; Flavonoids; Glycosides; Phytochemicals; Anti-Infective Agents
PubMed: 38005389
DOI: 10.3390/molecules28227666 -
Frontiers in Cellular and Infection... 2023is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While...
is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.
Topics: Animals; Humans; Child; Child, Preschool; Cryptosporidiosis; CD40 Ligand; Gastrointestinal Microbiome; Cryptosporidium; Intestines; Immunologic Deficiency Syndromes; Parasites; Cryptosporidium parvum; Bacteria; Propionibacterium acnes
PubMed: 37965266
DOI: 10.3389/fcimb.2023.1281440 -
Brazilian Journal of Cardiovascular... Nov 2023In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic...
In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.
PubMed: 37947185
DOI: 10.21470/1678-9741-2023-0186 -
Surgical Neurology International 2023Cervical vertebral osteomyelitis (CVO) is a rare pathology that leads to progressive osseous degradation and eventual loss of bone putting the patient at risk of...
BACKGROUND
Cervical vertebral osteomyelitis (CVO) is a rare pathology that leads to progressive osseous degradation and eventual loss of bone putting the patient at risk of devastating neurological injury in the event of bony collapse or instability. formerly called is rare, but within the last two decades has been an increasingly reported cause of osteomyelitis. The majority of vertebral osteomyelitis cases have been reported in patients with a history of prior invasive procedures where direct contamination at the time of procedure was suspected as the underlying etiology.
CASE DESCRIPTION
We report a unique case of an otherwise healthy 39-year-old male with no prior history of invasive procedures who presented with CVO secondary to . He underwent surgical debridement and fusion in conjunction with antibiotic treatment. The patient recovered well and a 2-year follow-up with serial imaging showed no evidence of disease recurrence.
CONCLUSION
is an under-recognized and under-reported etiology of spine infections. Clinicians should be aware of the pathological potential and atypical presentation of vertebral osteomyelitis.
PubMed: 37941631
DOI: 10.25259/SNI_542_2023 -
Unveiling the dynamics of the breast milk microbiome: impact of lactation stage and gestational age.Journal of Translational Medicine Nov 2023Breast milk (BM) provides complete nutrition for infants for the first six months of life and is essential for the development of the newborn's immature immune and...
BACKGROUND
Breast milk (BM) provides complete nutrition for infants for the first six months of life and is essential for the development of the newborn's immature immune and digestive systems. While BM was conventionally believed to be sterile, recent advanced high throughput technologies have unveiled the presence of diverse microbial communities in BM. These insights into the BM microbiota have mainly originated from uncomplicated pregnancies, possibly not reflecting the circumstances of mothers with pregnancy complications like preterm birth (PTB).
METHODS
In this article, we investigated the BM microbial communities in mothers with preterm deliveries (before 37 weeks of gestation). We compared these samples with BM samples from healthy term pregnancies across different lactation stages (colostrum, transitional and mature milk) using 16S rRNA gene sequencing.
RESULTS
Our analysis revealed that the microbial communities became increasingly diverse and compositionally distinct as the BM matured. Specifically, mature BM samples were significantly enriched in Veillonella and lactobacillus (Kruskal Wallis; p < 0.001) compared to colostrum. The comparison of term and preterm BM samples showed that the community structure was significantly different between the two groups (Bray Curtis and unweighted unifrac dissimilarity; p < 0.001). Preterm BM samples exhibited increased species richness with significantly higher abundance of Staphylococcus haemolyticus, Propionibacterium acnes, unclassified Corynebacterium species. Whereas term samples were enriched in Staphylococcus epidermidis, unclassified OD1, and unclassified Veillonella among others.
CONCLUSION
Our study underscores the significant influence of pregnancy-related complications, such as preterm birth (before 37 weeks of gestation), on the composition and diversity of BM microbiota. Given the established significance of the maternal microbiome in shaping child health outcomes, this investigation paves the way for identifying modifiable factors that could optimize the composition of BM microbiota, thereby promoting maternal and infant health.
Topics: Infant; Pregnancy; Female; Child; Infant, Newborn; Humans; Milk, Human; Gestational Age; Premature Birth; RNA, Ribosomal, 16S; Lactation; Microbiota
PubMed: 37932773
DOI: 10.1186/s12967-023-04656-9 -
Scientific Reports Oct 2023Prodigiosin, a red pigment produced by Hahella chejuensis, a marine-derived microorganism, has several biological functions, including antimicrobial activity and...
Prodigiosin, a red pigment produced by Hahella chejuensis, a marine-derived microorganism, has several biological functions, including antimicrobial activity and inflammatory relief. In this study, the antibacterial activity of prodigiosin against skin microorganisms was explored. Paper disc assay on skin bacterial cells revealed that Cutibacterium acnes related to acne vulgaris highly susceptible to prodigiosin. MIC (Minimal Inhibitory Concentration) and MBC (Minimal Bactericidal Concentration) were determined on Cutibacterium species. The RNA-seq analysis of prodigiosin-treated C. acnes cells was performed to understand the antibacterial mechanism of prodigiosin. Among changes in the expression of hundreds of genes, the expression of a stress-responsive sigma factor encoded by sigB increased. Conversely, the gene expression of cell wall biosynthesis and energy metabolism was inhibited by prodigiosin. Specifically, the expression of genes related to the metabolism of porphyrin, a pro-inflammatory metabolite, was significantly reduced. Therefore, prodigiosin could be used to control C. acnes. Our study provided new insights into the antimicrobial mechanism of prodigiosin against C. acnes strains.
Topics: Humans; Prodigiosin; Transcriptome; Anti-Bacterial Agents; Acne Vulgaris; Microbial Sensitivity Tests; Propionibacterium acnes
PubMed: 37833344
DOI: 10.1038/s41598-023-44612-7 -
Indian Journal of Dermatology 2023The study of antimicrobial-resistant was not conducted regularly, especially in Indonesia. Conversely, regular monitoring of antibiotic efficacy through testing to...
The study of antimicrobial-resistant was not conducted regularly, especially in Indonesia. Conversely, regular monitoring of antibiotic efficacy through testing to assess the evolution of current resistance patterns is obligated; thus, filling the gap caused by a lack of appropriate antibiotic surveillance is required. Analyse the correlation between resistance patterns of to doxycycline, clindamycin, erythromycin and azithromycin with the severity of acne vulgaris. This is an analytic observational laboratory study with a cross-sectional design of mild to severe acne vulgaris (AV) patients. Specimens were obtained from comedones of 71 patients, which were cultured and identified using biochemical examination. Antimicrobial resistance (doxycycline, clindamycin, erythromycin and azithromycin) to was tested by disc diffusion method. Among 71 samples collected, 40 (56.3%) isolates were cultured and identified. The incidence of resistance to more than one antimicrobial was 45%. Antimicrobial resistances were clindamycin 42.5%, erythromycin 40%, azithromycin 23.5% and doxycycline 12.5%, respectively. According to the contingency coefficient test, there was moderate correlation between the resistance pattern of to clindamycin ( = 0.485, = <0.001) and doxycycline ( = 0.433, = 0.002) and AV severity. There was weak correlation between the resistance pattern of to erythromycin ( = 0.333; = 0.025) and azithromycin ( = 0.321; = 0.032) and AV severity. In conclusion, there is a correlation between the pattern of resistance to doxycycline, clindamycin, erythromycin, azithromycin and severity of AV.
PubMed: 37822407
DOI: 10.4103/ijd.ijd_623_22 -
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