Scalp microbiome composition changes and pathway evaluations due to effective treatment with Piroctone Olamine shampoo.

OBJECTIVE: To characterize the scalp microbial composition, function, and connection to dandruff severity using a metagenomics approach and to understand the impact of a Piroctone Olamine containing anti-dandruff shampoo on the scalp microbiome. METHODS: Shotgun metagenomics was used to characterize the composition of the scalp microbiomes from 94 subjects with and without clinically defined dandruff. Furthermore, the microbiome of the scalps of 100 dandruff sufferers before and after 3 weeks of treatment with either control or anti-dandruff shampoo containing 0.5% Piroctone Olamine (PO) was characterized and compared to identify microorganisms associated with the dandruff condition and the associated pathways and processes that may contribute to PO's effect on scalp microbiome. RESULTS: A higher relative abundance of Malassezia restricta and Staphylococcus capitis and a lower abundance of Cutibacterium acnes were associated with the dandruff scalps relative to the no-dandruff scalps. A 3-week PO shampoo treatment reduced the relative abundance of Malassezia species and Staphylococcus capitis and increased the relative abundance of Cutibacterium acnes. This change to the scalp microbiome composition is consistent with a return to a healthy no-dandruff microbiome and improved clinical signs and symptoms as measured by adherent scalp flaking score (ASFS) compared with the control shampoo. Functional genomics analysis showed that the PO shampoo treatment reduced oxidative stress-associated genes and decreased the abundance of protease, urease, and lipase genes. These changes correlated positively to improvements in dandruff severity. PO treatment favourably shifted scalp microbiomes in dandruff subjects toward the no-dandruff state. CONCLUSION: Our results suggest that part of the aetiology of dandruff can be attributed to dysbiosis of the scalp microbiome. PO treatment can restore a healthier microbiome, reducing oxidative stress and promoting better scalp health.

OBJECTIF: Caractériser la composition microbienne du cuir chevelu, sa fonction et son lien avec la sévérité des pellicules à l'aide d'une approche métagénomique. Comprendre l'impact d'un shampooing antipelliculaire à base de piroctone olamine sur le microbiome du cuir chevelu. MÉTHODES: La métagénomique shotgun a été utilisée pour caractériser la composition des microbiomes du cuir chevelu de 94 sujets avec et sans pellicules définies cliniquement. Par ailleurs, le microbiome des cuirs chevelus de 100 personnes ayant des pellicules avant et après trois semaines de traitement par un shampooing témoin ou un shampooing antipelliculaire contenant 0,5 % de piroctone olamine (PO) a été caractérisé et comparé pour identifier les micro­organismes associés à l'état pelliculaire, et les voies et processus associés pouvant contribuer à l'effet de la PO sur le microbiome du cuir chevelu. RÉSULTATS: Une abondance relative plus élevée de Malassezia restricta et de Staphylococcus capitis, et une abondance plus faible de Cutibacterium acnes étaient associées aux cuirs chevelus avec des pellicules par rapport aux cuirs chevelus sans pellicules. Un traitement avec un shampooing contenant de la PO de 3 semaines a réduit l'abondance relative des espèces Malassezia et Staphylococcus capitis, et a augmenté l'abondance relative de Cutibacterium acnes. Cette modification de la composition du microbiome du cuir chevelu est cohérente avec un retour à un microbiome sain sans pellicules, et une amélioration des signes et symptômes cliniques mesurés par le score de desquamation du cuir chevelu adhérent (Adherent Scalp Flaking Score, ASFS) par rapport au shampooing témoin. L'analyse génomique fonctionnelle a montré que le traitement avec un shampooing contenant de la PO réduisait les gènes associés au stress oxydatif et diminuait l'abondance des gènes de la protéase, de l'uréase et de la lipase. Ces modifications étaient corrélées positivement à des améliorations de la sévérité des pellicules. Le traitement avec la PO a favorisé l'évolution des microbiomes du cuir chevelu des sujets ayant des pellicules vers un état sans pellicules. CONCLUSION: Nos résultats suggèrent qu'une partie de l'étiologie des pellicules peut être attribuée à la dysbiose du microbiome du cuir chevelu. Le traitement avec la PO peut rétablir un microbiome plus sain, en réduisant le stress oxydatif et en favorisant une meilleure santé du cuir chevelu.

Scalp Condition Impacts Hair Growth and Retention via Oxidative Stress.

Conventionally, the medical focus has been either on hair loss or the condition of the scalp in terms of specific dermatological diseases. Indeed, the proximate structural arrangement of the scalp and hair leads to an interdependent relationship between the two. While protective benefits of the hair to the scalp are obvious, the role of the scalp as an incubatory environment for the preemergent hair fiber has largely been ignored. In fact, there is a wealth of observational data on specific dermatological conditions of the scalp providing evidence for the role of the scalp condition in supporting the production of healthy hair. Oxidative stress, the inability of the body to sufficiently counteract the sources of oxidation, is prevalent in many skin conditions, including normal skin aging. On the scalp, the hair appears to be impacted prior to emergence, and oxidative stress appears to play a role in premature hair loss. The scalp commensal organism, Malassezia, has been recognized to be a source of oxidative damage. Therefore, hair care products, specifically shampoos, with active Malassezia inhibitory agents, such as zinc pyrithione, tend to reduce premature hair loss, besides the known benefits in treating specific dermatologic scalp pathologies, and therefore should represent an integral part of every treatment regimen for hair loss, even in individuals not showing symptoms of scalp pathologies.

The significance of "indefinite for dysplasia" grading in Barrett metaplasia.

CONTEXT: For a confident diagnosis of dysplasia in Barrett metaplasia, the epithelial atypia should also involve the surface epithelium. However, pathologists are often faced with biopsies where the crypts show dysplasia, but the surface epithelium is either uninvolved or unevaluable. We previously grouped these cases with indefinite for dysplasia (IND). OBJECTIVE: To determine the clinical significance of IND grading in Barrett metaplasia. DESIGN: All biopsies from 276 prospectively followed patients with Barrett metaplasia, who did not have high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) on initial biopsy, were graded as negative for dysplasia, IND, low-grade dysplasia (LGD), HGD, and EAC. Biopsies with multifocal IND or LGD were graded as INDM or LGDM, respectively. RESULTS: Only 3 of 193 patients (2%) with an initial diagnosis of negative for dysplasia and only 1 of 48 patients (2%) diagnosed with IND progressed to HGD or EAC. By contrast, 1 of 7 patients (14%) with INDM, 2 of 21 (10%) with LGD, and 1 of 7 (14%) with LGDM progressed to HGD or EAC. There was no significant difference in progression rate between patients with an initial diagnosis of negative for dysplasia and those diagnosed IND nor were there significant differences among patients with initial diagnoses of INDM, LGD, or LGDM. Kaplan-Meier analysis showed that patients with INDM, LGD, or LGDM on initial biopsy (group 1) were more likely to progress to HGD or EAC than were those patients who were diagnosed negative for dysplasia or IND (group 2; log-rank test, P < .001). CONCLUSIONS: Multifocal IND in an esophageal biopsy from a patient with Barrett metaplasia has the same clinical implication as LGD.

Oral bisphosphonate prescriptions and the risk of esophageal adenocarcinoma in patients with Barrett's esophagus.

BACKGROUND: Recent case reports suggested a link between oral bisphosphonate use and esophageal cancer. We therefore examined the association between these medications and the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). DESIGN: This was a nested, matched case-control study. Cases with incident EAC at least 6 months following BE index date were matched by incidence density sampling to controls with BE without EAC. Patients with BE were found in the national Department of Veterans Affairs computerized databases, and each filled prescriptions for oral bisphosphonates between BE diagnosis and EAC diagnosis (or corresponding dates in controls). Incidence density ratios were calculated using conditional logistic regression models. RESULTS: In a cohort of 11,823 patients with BE, we compared 116 cases and 696 controls. Most were men (97%). Most cases and controls had at least one filled proton pump inhibitor (PPI) prescription (95 vs. 94%, P = 0.5). Filled bisphosphonate prescriptions were very uncommon (1.7 vs. 1.9%) and were not associated with EAC; the incidence density ratio was 0.92 (95% CI, 0.21-4.15). CONCLUSION: In patients with BE, oral bisphosphonates were not associated with an increased risk of EAC.

Goblet cell mimickers in esophageal biopsies are not associated with an increased risk for dysplasia.

CONTEXT: Identification of intestinal-type goblet cells (ITGCs) in hematoxylin-eosin-stained sections of esophageal biopsies is essential for the diagnosis of Barrett metaplasia. However, we have seen cases diagnosed as Barrett metaplasia based solely on cells that pose morphologic similarity to ITGCs on hematoxylin-eosin staining or stain positive with Alcian blue. OBJECTIVE: To determine the clinical significance of goblet cell mimickers. DESIGN: Initial biopsies from 78 patients with original diagnosis of Barrett metaplasia negative for dysplasia and a mean follow-up of 72 months were reviewed and reclassified into 3 categories: (1) ITGCs, (2) goblet cell mimickers, or (3) neither. Sections from available paraffin blocks were stained with Alcian blue at pH 2.5. The presence of the different types of cells and positive Alcian blue staining were correlated with each other and evaluated for their significance as predictors of progression to dysplasia. RESULTS: Goblet cell mimickers were present in 35 cases and were associated with ITGCs in the same biopsy in 23 (66%) of these cases. Intestinal-type goblet cells were present in 56 cases, and the remaining 10 cases, although called Barrett on the original report, did not show either ITGCs or goblet cell mimickers. Only the presence of ITGCs was associated with significant risk for dysplasia (P = .008). Positive Alcian blue staining was not associated with a significant risk for dysplasia. CONCLUSIONS: Our results indicate that the diagnosis of Barrett metaplasia should be rendered with confidence only when ITGCs are identified on routine hematoxylin-eosin-stained sections.