-
Frontiers in Molecular Biosciences 2023Atopic dermatitis (AD) is a common, chronic and relapsing inflammatory skin disease with various clinical presentations and combinations of symptoms. The pathophysiology... (Review)
Review
Atopic dermatitis (AD) is a common, chronic and relapsing inflammatory skin disease with various clinical presentations and combinations of symptoms. The pathophysiology of AD is complex and multifactorial. There are several factors involved in the etiopathogenesis of AD including structural and immunological epidermal barrier defect, imbalance of the skin microbiome, genetic background and environmental factors. Alterations in structural proteins, lipids, proteases, and their inhibitors, lead to the impairment of the stratum corneum which is associated with the increased skin penetration and transepidermal water loss. The elevated serum immunoglobulin E levels and blood eosinophilia have been shown in the majority of AD patients. Type 2 T-helper cell immune pathway with increased expression of interleukin (IL)-4, IL-5, and IL-13, has an important role in the etiopathogenesis of AD. Both T cells and keratinocytes contribute to epidermal barrier impairment in AD via a dynamic interaction of cytokines and chemokines. The skin microbiome is another factor of relevance in the etiopathogenesis of AD. It has been shown that during AD flares, () colonization increased, while () decreased. On the contrary, and species of , Corynebacterium and Propionibacterium increased during the remision phases. However, it is not clear whether skin dysbiosis is one of the symptoms or one of the causes of AD. There are several therapeutic options, targeting these pathways which play a critical role in the etiopathogenesis of AD. Although topical steroids are the mainstay of the treatment of AD, new biological therapies including IL-4, IL-13, and IL-31 inhibitors, as well as Janus kinase inhibitors (JAKi), increasingly gain more importance with new advances in the therapy of AD. In this review, we summarize the role of immunological and structural epidermal barrier dysfunction, immune abnormalities, impairment of lipids, filaggrin mutation and skin microbiome in the etiopathogenesis of AD, as well as the therapeutic options for AD and their effects on these abnormalities in AD skin.
PubMed: 37654796
DOI: 10.3389/fmolb.2023.1159404 -
Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances.Biochemistry and Biophysics Reports Dec 2023Globally, Acne Vulgaris is a widespread, chronic inflammatory condition of the pilosebaceous follicles. Acne is not fatal, but depending on its severity, it can leave... (Review)
Review
BACKGROUND
Globally, Acne Vulgaris is a widespread, chronic inflammatory condition of the pilosebaceous follicles. Acne is not fatal, but depending on its severity, it can leave the sufferer with scars, irritation, and significant psychological effects (including depression). In the current review, we have included various factors for acne and their treatment explained. It also narrated the current medicament and the new investigation dosage forms with clinical phases information provided.
MAIN BODY OF THE ABSTRACT
Acne's pathophysiology involves four important factors: excessive sebum production, hyperkeratinization of pilosebaceous follicles, hyperproliferation of propionibacterium acnes (P. acnes), and inflammation. Identifying both inflammatory (Papule, pustule, nodule, and cyst) and non-inflammatory (black heads, white heads) acne lesions is necessary for diagnosing and treating acne vulgaris.
SHORT CONCLUSION
In this review, traditional therapy approaches such as topical (i.e., retinoids and antibiotics), systemic (i.e., retinoids, antibiotics, and hormonal), and physical therapies are briefly discussed. In addition, we highlight the issues posed by P. acne's resistance to the antibiotics used in commercially available medications and the necessity for novel therapeutic techniques. Finally, we examined a few innovative acne therapies pending clinical trial approval and commercial acne medications.
PubMed: 38076662
DOI: 10.1016/j.bbrep.2023.101578 -
Journal of the European Academy of... Apr 2024Acne vulgaris is a chronic inflammatory skin disease with a complex pathogenesis. Traditionally, the primary pathophysiologic factors in acne have been thought to be:... (Review)
Review
Acne vulgaris is a chronic inflammatory skin disease with a complex pathogenesis. Traditionally, the primary pathophysiologic factors in acne have been thought to be: (1) altered sebum production, (2) inflammation, (3) excess keratinization and (4) colonization with the commensal Cutibacterium acnes. However, the role of C. acnes has been unclear, since virtually all adults have C. acnes on their skin yet not all develop acne. In recent years, understanding of the role of C. acnes has expanded. It is still acknowledged to have an important place in acne pathogenesis, but evidence suggests that an imbalance of individual C. acnes phylotypes and an alteration of the skin microbiome trigger acne. In addition, it is now believed that Staphylococcus epidermidis is also an actor in acne development. Together, C. acnes and S. epidermidis maintain and regulate homeostasis of the skin microbiota. Antibiotics, which have long been a staple of acne therapy, induce cutaneous dysbiosis. This finding, together with the long-standing public health edict to spare antibiotic use when possible, highlights the need for a change in acne management strategies. One fertile direction of study for new approaches involves dermocosmetic products that can support epidermal barrier function and have a positive effect on the skin microbiome.
Topics: Humans; Acne Vulgaris; Skin; Microbiota; Dermatitis; Dysbiosis; Anti-Bacterial Agents; Propionibacterium acnes
PubMed: 37777343
DOI: 10.1111/jdv.19540 -
Dermatology and Therapy Jan 2024The skin microbiome consists of the microorganisms populating the human skin. Cutibacterium acnes (C. acnes, formerly named Propionibacterium acnes) is recognized as a... (Review)
Review
The skin microbiome consists of the microorganisms populating the human skin. Cutibacterium acnes (C. acnes, formerly named Propionibacterium acnes) is recognized as a key factor in acne development, regulating inflammatory and immune pathways. Dysbiosis has been described as the imbalance in skin microbiome homeostasis and may play a role in acne pathogenesis. Microbial interference has been shown to be a contributor to healthy skin homeostasis and staphylococcal strains may exclude acne-associated C. acnes phylotypes. In this review we present an update on the skin microbiome in acne and discuss how current acne treatments such as benzoyl peroxide, orally administered isotretinoin, and antibiotics may affect the skin microbiome homeostasis. We highlight the collateral damage of acne antibiotics on the skin microbiome, including the risk of antimicrobial resistance and the dysregulation of the microbiome equilibrium that may occur even with short-term antibiotic courses. Consequently, the interest is shifting towards new non-antibiotic pharmacological acne treatments. Orally administered spironolactone is an emerging off-label treatment for adult female patients and topical peroxisome proliferator-activated receptor gamma (PPARγ) modulation is being studied for patients with acne. The potential application of topical or oral probiotics, bacteriotherapy, and phage therapy for acne are further promising areas of future research.
PubMed: 38183614
DOI: 10.1007/s13555-023-01079-8 -
Pharmaceutics Jul 2023Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and (CA: formerly ) hyperproliferation in pilosebaceous follicles....
Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and (CA: formerly ) hyperproliferation in pilosebaceous follicles. This study evaluated the efficacy of FRO, a formula composed of fermented Stokes and , against acne pathogenesis via antimicrobial assessment and an in vitro analysis. Stimulated model cells treated with hormones, CA, or lipopolysaccharide (LPS) were designed based on the characteristics of acne pathogenesis, including inflammation and sebum hypersecretion. High-performance liquid chromatography, disc diffusion, MTS, and western blotting assays were used to examine potential anti-acne effects. FRO was determined to contain phenolics such as gallic acid, fisetin, quercetin, and kaempferol. FRO exerted antimicrobial activity against CA and inhibited reactive oxygen species production that was otherwise increased by LPS or CA in HaCaT cells. Additionally, FRO exerted anti-inflammatory effects by inhibiting iNOS, TNF-α, IL-6, p-STAT-3, and p-NF-κB, which were previously upregulated by LPS or CA in THP-1 and HaCaT cells. FRO inhibited lipogenesis induced by steroid hormones and CA by decreasing FAS and SREBP-1 levels in sebocytes. Additionally, FRO down-regulated the androgen receptor, 5α-reductase, SREBP-1, and FAS levels, which were upregulated by steroid hormone in LNCaP cells. Taken together, our findings suggest that FRO alleviates acne by inhibiting the growth of CA, inflammation, and excess sebum and could be used for functional cosmetics or acne treatments.
PubMed: 37514071
DOI: 10.3390/pharmaceutics15071885 -
International Journal of Dermatology Mar 2024Antibiotics have constituted the mainstay of acne therapy despite acne being classified as an inflammatory disorder. The indiscriminate usage of antibiotics over the... (Review)
Review
Antibiotics have constituted the mainstay of acne therapy despite acne being classified as an inflammatory disorder. The indiscriminate usage of antibiotics over the years has thus fueled the issue of antimicrobial resistance. Cutibacterium acnes (C. acnes) can acquire resistance due to chromosomal mutation or genetic acquisition. C. acnes can transfer resistance to other resident flora, complicating the management of skin and soft tissue infections. It can also transfer resistant strains to other body sites and to immunocompromised and elderly patients thus putting them at risk of serious infections. Recent studies have highlighted the physiologic role of C. acnes in maintaining the normal homeostasis of the skin microbiome. The role of Malassezia in causation of acne has piqued interest in recent times. The efficacy of antibiotics in acne is attributed to their para-antibiotic, anti-inflammatory action rather than antimicrobial action. Thus, usage of low-dose antibiotics and alternatives to antibiotics has been advocated. Some alternative therapies showing efficacy in acne are probiotics, oral zinc, precision therapy using succinic acid, bacteriophages, and anti-biofilm therapy like myrtacin, topical azelaic acid, and salicylic acid. Using isotretinoin in early stages of acne can reduce the incidence of scarring and alleviate the need for antibiotics. Thus, a gradual shift from antibiotics to alternative therapies in acne is the need of the hour.
Topics: Humans; Aged; Anti-Bacterial Agents; Acne Vulgaris; Isotretinoin; Skin; Salicylic Acid; Propionibacterium acnes
PubMed: 37743606
DOI: 10.1111/ijd.16854 -
Microbial Pathogenesis Dec 2023Dental caries is a result of the ecological dysfunction of the polymicrobial community on the tooth surface, which evolves through microbial interactions. In this study,...
OBJECTIVES
Dental caries is a result of the ecological dysfunction of the polymicrobial community on the tooth surface, which evolves through microbial interactions. In this study, we conducted a thorough analysis of the dental plaque microbiome to comprehend its multi-microbial aetiology.
MATERIALS AND METHOD
In this study, plaque was collected from healthy tooth surfaces, shallow carious teeth and deep carious teeth, and bacterial composition and abundance were assessed using 16S rRNA high-throughput sequencing. Random forest and LEfSe were used to profile various microorganisms at each stage. Additionally, we developed a molecular ecological network (MEN) based on random matrix theory (RMT) to examine microbial interactions for the first time.
RESULTS
Our results reveal that Scardovia wiggsiae, Streptococcus mutans, and Propionibacterium acidifaciens may be associated with initial caries, and Propionibacterium acidifaciens differentiates between shallow and deep caries. As caries progressed, the alpha diversity index declined, indicating a decrease in microbial variety. The network topological indices such as centralization betweenness revealed that the caries network had become more complex, involving more microbial interactions. The shallow network revealed a high negative correlation ratio across nodes, indicating that microbes competed heavily. In contrast, the positive correlation ratio of deep network nodes was high, and microorganisms transitioned from a competitive to a synergistic state.
CONCLUSIONS
This study suggests that microbial diversity and interactions are critical to caries progression and that future caries research should give greater consideration to the role of microbial interaction factors in caries progression.
Topics: Humans; Dental Caries; RNA, Ribosomal, 16S; Dental Plaque; Streptococcus mutans; Microbiota
PubMed: 37858633
DOI: 10.1016/j.micpath.2023.106390 -
Journal of Endodontics Jul 2023This scoping review aimed to map the evidence about the microbiota found in persistent endodontic infections. (Review)
Review
INTRODUCTION
This scoping review aimed to map the evidence about the microbiota found in persistent endodontic infections.
METHODS
The study protocol was prospectively registered and is available at https://osf.io/3g2cp. The electronic search was performed in MEDLINE via PubMed, Lilacs, BBO, Scopus, Web of Science, Cochrane Library, and Embase. The eligibility criteria were based on the PCC acronym, where P (Population) represents patients with teeth presenting persistent endodontic infection, C (Concept) represents microbial profile, and C (Context) represents undergoing endodontic retreatment. Clinical studies that evaluated the microbial profile of samples collected from root canals of teeth undergoing retreatment, using classical or molecular methods, were included. Studies that did not show a minimum period of 1 year between primary endodontic treatment and retreatment or did not radiographically evaluate the quality of primary root canal filling were excluded. Two reviewers independently selected the articles and collected data.
RESULTS
From a total of 957 articles, 161 were read in full, and 32 studies were included. The most prevalent species were Enterococcus faecalis, Parvimonas micra, Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, Dialister invisus, Propionibacterium acnes, Tannerella forsythia, and Treponema denticola. Cases with symptomatology or inadequate root canal filling presented an increase in specific bacterial species compared to those with no symptomatology or adequate filling. A greater number of microorganisms was observed in teeth with inadequate coronal restoration compared to those with adequate restoration.
CONCLUSIONS
Persistent endodontic infections have a polymicrobial profile identified by the commonly used methods for bacterial detection/identification and are subject to the limitations present in each of those methods.
Topics: Humans; Dental Pulp Cavity; Porphyromonas gingivalis; Prevotella intermedia; Porphyromonas endodontalis
PubMed: 37211309
DOI: 10.1016/j.joen.2023.05.010 -
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 2023This study was designed to explore the composition of the intestinal microbiota and its longitudinal variation between the second trimester (T2) and the third trimester... (Observational Study)
Observational Study
Composition of the intestinal microbiota and its variations between the second and third trimesters in women with gestational diabetes mellitus and without gestational diabetes mellitus.
OBJECTIVE
This study was designed to explore the composition of the intestinal microbiota and its longitudinal variation between the second trimester (T2) and the third trimester (T3) in women with gestational diabetes mellitus (GDM) and pregnant women with normal glucose tolerance.
METHODS
This observational study was conducted at Peking Union Medical College Hospital (PUMCH). Women with GDM and pregnant women with normal glucose tolerance were enrolled in the study, and fecal samples were collected during T2 (weeks 24~28) and T3 (weeks 34~38). Fecal samples were analyzed from 49 women with GDM and 42 pregnant women with normal glucose tolerance. The 16S rRNA gene amplicon libraries were sequenced to analyze the microbiota and QIIME2 was used to analyze microbiome bioinformatics.
RESULTS
The four dominant phyla that , , and which accomplish about 99% of the total relative abundance did not significantly change between the T2 and T3 in the GDM and healthy groups. At the genus level, the relative abundance of (0 vs. 0.25%, P = 0.041) and (0 vs. 0.29%, P = 0.041) increased significantly in the control group, but not in the GDM group. At the phylum level, the relative abundance of and was significantly different between women with GDM and pregnant women with normal glucose tolerance in both T2 and T3. In T2 and T3, the relative abundances of , , and were significantly higher in the GDM group than in the control group (P<0.05). The relative abundance of in the GDM group was lower than in the control group in both T2 and T3.
CONCLUSIONS
The intestinal microbiota composition was stable from T2 to T3 in the GDM and control groups; however, the intestinal microbiota composition was different between the two groups.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Pregnancy Trimester, Third; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Blood Glucose; Glucose; Bacteria; Actinobacteria
PubMed: 37522117
DOI: 10.3389/fendo.2023.1126572