Characterization of Skin-Resident Microbiota in Inflammatory Cutaneous Disease

The skin is the largest organ in the human body, approximately 1.5 to 2 m2 in area, and serves as a crucial physical and immune barrier from our environment. Yet, the skin is home to billions of microorganisms inhabiting a multitude of folds, invaginations, and specialized niches that sustain microscopic life (Grice and Segre, 2011; Scharschmidt and Fischbach, 2013). We are not teeming with bugs so much as we are irrevocably intertwined with microbiota such that, throughout evolutionary history, these bacteria, fungi, and viruses have become invaluable parts of our physiology, cooperatively acting as a hidden organ. The microbiota colonizing the skin, their genetic material, and their microenvironments are collectively referred to as the skin microbiome (Marchesi and Ravel, 2015). Most microorganisms are not pathogens. Rather, the majority of microorganisms living on their hosts are benign and, in some cases, beneficial, performing functions vital for host physiology and homeostasis. Scientists are beginning to unravel how the skin microbiome is interfacing with different physiological processes of the mammalian host. Microbiota living on us, but also residing within deeper layers of the skin, contribute to host inflammation, epidermal barrier function, and immunity through feedback mechanisms with our immune cells (Grice and Segre, 2011). Microbiota even contribute to host defense through the production of bactericidal factors (Iacob et al., 2018; Jacobs et al., 2017; Nakatsuji et al., 2017; Zheng et al., 2020). Microbiome researchers are interested in understanding these mechanisms that link commensal microbes with host biology and how these interactions contribute to host health or disease. This thesis aims to characterize resident skin microbiota communities the context of inflammatory cutaneous disease

The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility

Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects the elderly. An altered skin microbiota in BP was recently revealed. Accumulating evidence points toward a link between the gut microbiota and skin diseases; however, the gut microbiota composition of BP patients remains largely underexplored, with only one pilot study to date, with a very limited sample size and no functional profiling of gut microbiota. To thoroughly investigate the composition and function of the gut microbiota in BP patients, and explore possible links between skin conditions and gut microbiota, we here investigated the gut microbiota of 66 patients (81.8% firstly diagnosed) suffering from BP and 66 age-, sex-, and study center-matched controls (CL) with non-inflammatory skin diseases (132 total participants), using 16S rRNA gene and shotgun sequencing data. Decreased alpha-diversity and an overall altered gut microbial community is observed in BP patients. Similar trends are observed in subclassifications of BP patients, including first diagnoses and relapsed cases. Furthermore, we observe a set of BP disease-associated gut microbial features, including reduced Faecalibacterium prausnitzii and greater abundance of pathways related to gamma-aminobutyric acid (GABA) metabolism in BP patients. Interestingly, F. prausnitzii is a well-known microbiomarker of inflammatory diseases, which has been reported to be reduced in the gut microbiome of atopic dermatitis and psoriasis patients. Moreover, GABA plays multiple roles in maintaining skin health, including the inhibition of itching by acting as a neurotransmitter, attenuating skin lesions by balancing Th1 and Th2 levels, and maintaining skin elasticity by increasing the expression of type I collagen. These findings thus suggest that gut microbiota alterations present in BP may play a role in the disease, and certain key microbes and functions may contribute to the link between gut dysbiosis and BP disease activity. Further studies to investigate the underlying mechanisms of the gut-skin interaction are thus clearly warranted, which could aid in the development of potential therapeutic interventions

Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms

Background The interplay between hosts and their associated microbiome is now recognized as a fundamental basis of the ecology, evolution, and development of both players. These interdependencies inspired a new view of multicellular organisms as “metaorganisms.” The goal of the Collaborative Research Center “Origin and Function of Metaorganisms” is to understand why and how microbial communities form long-term associations with hosts from diverse taxonomic groups, ranging from sponges to humans in addition to plants. Methods In order to optimize the choice of analysis procedures, which may differ according to the host organism and question at hand, we systematically compared the two main technical approaches for profiling microbial communities, 16S rRNA gene amplicon and metagenomic shotgun sequencing across our panel of ten host taxa. This includes two commonly used 16S rRNA gene regions and two amplification procedures, thus totaling five different microbial profiles per host sample. Conclusion While 16S rRNA gene-based analyses are subject to much skepticism, we demonstrate that many aspects of bacterial community characterization are consistent across methods. The resulting insight facilitates the selection of appropriate methods across a wide range of host taxa. Overall, we recommend single- over multi-step amplification procedures, and although exceptions and trade-offs exist, the V3 V4 over the V1 V2 region of the 16S rRNA gene. Finally, by contrasting taxonomic and functional profiles and performing phylogenetic analysis, we provide important and novel insight into broad evolutionary patterns among metaorganisms, whereby the transition of animals from an aquatic to a terrestrial habitat marks a major event in the evolution of host-associated microbial composition

Validation of diagnostic ICHD-3 criteria for menstrual migraine

Objective: To assess validity of ICHD-3 diagnostic criteria for menstrual migraine. Methods: We performed a longitudinal E-diary study in premenopausal women with migraine. Menstrual migraine diagnosis was self-reported at baseline, and verified according to diary based ICHD-3 criteria and a previous proposed statistical model. Validity of self-reported menstrual migraine was compared to diary based diagnosis and statistical diagnosis. Test-retest reliability and concordance between both methods were determined. Clinical characteristics of perimenstrual and non-perimenstrual migraine attacks were compared in women with and without menstrual migraine. Results: We included 607 women. Both women who did and women who did not self-report to suffer from menstrual migraine fulfilled ICHD-3 criteria in the E-diary in two thirds of cases. Pure menstrual migraine was extremely rare (<1%). Concordance between statistical and diary based diagnosis was minimal (κ = 0.28, 95% CI:0.23–0.33). Women diagnosed with menstrual migraine showed 37–50% longer attack duration and increased triptan intake (OR 1.19–1.22, p < 0.001) during perimenstrual attacks. Conclusion: Self-reported menstrual migraine diagnosis has extremely poor accuracy. Two thirds of women suffer from menstrual migraine, independent of self-reports. Pure menstrual migraine is rare. Women with menstrual migraine have longer attack duration and increased triptan intake during perimenstrual attacks, in contrast to women without menstrual migraine. Prospective headache (E-)diaries are required for a menstrual migraine diagnosis, also in clinical practice

Characterization of the skin microbiota in bullous pemphigoid patients and controls reveals novel microbial indicators of disease

Abstract Introduction: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It predominately afflicts the elderly and is significantly associated with increased mortality. The observation of age-dependent changes in the skin microbiota as well as its involvement in other inflammatory skin disorders suggests that skin microbiota may play a role in the emergence of BP blistering. We hypothesize that changes in microbial diversity associated with BP might occur before the emergence of disease lesions, and thus could represent an early indicator of blistering risk. Objectives: The present study aims to investigate potential relationships between skin microbiota and BP and elaborate on important changes in microbial diversity associated with blistering in BP. Methods: The study consisted of an extensive sampling effort of the skin microbiota in patients with BP and age- and sex-matched controls to analyze whether intra-individual, body site, and/or geographical variation correlate with changes in skin microbial composition in BP and/or blistering status. Results: We find significant differences in the skin microbiota of patients with BP compared to that of controls, and moreover that disease status rather than skin biogeography (body site) governs skin microbiota composition in patients with BP. Our data reveal a discernible transition between normal skin and the skin surrounding BP lesions, which is characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, Staphylococcus aureus is ubiquitously associated with BP disease status, regardless of the presence of blisters. Conclusion: The present study suggests Staphylococcus aureus may be a key taxon associated with BP disease status. Importantly, we however find contrasting patterns in the relative abundances of Staphylococcus hominis and Staphylococcus aureus reliably discriminate between patients with BP and matched controls. This may serve as valuable information for assessing blistering risk and treatment outcomes in a clinical setting

Porous Inorganic Membranes for CO 2

INGENIERIE+MP