Comprehensive analysis of skin microbiome using Next generation sequencing in atopic dermatitis patients

Atopic dermatitis(AD) is a chronic,relapsing,and pruritic inflammatory skin disease characterised by distinct skin lesions often occurring alongside other allergic conditions. It affects approximately 10-20% of children and 2-8% of adults globally, making it one of the most prevalent chronic inflammatory dermatoses. AD poses a substantial burden, ranking 15th among all non-fatal diseases in terms of disability-adjusted life years(1).The prevalence of AD in India varies, with estimates ranging from 2% to 5% in children and 1% to 3% in adults (2).The relentless itching, pain, and visible skin lesions profoundly impact daily activities leading to emotional distress, social embarrassment,and sleep disturbances, thus severely compromising overall quality of life. This significant burden emphasises the need for newer and more treatment modalities to improve the management of AD and alleviate the profound suffering experienced by patients (3,4,5). AD arises from a complex pathogenesis involving genetic,immunologic, and environmental factors that lead to a compromised skin barrier and immune system dysregulation.Clinical presentation of lesions includes erythema,oedema,xerosis,excoriations,oozing,crusting and lichenification which vary according to patient’s age and chronicity (6). A complex microbial community termed “the microbiome” colonizes the skin, interacting with the host cells. It is integral for optimum skin barrier function and immune modulation. It exhibits considerable interindividual variation influenced by factors such as genetics, environment, lifestyle, and disease status (7,8). Dysbiosis of the skin microbiome is associated with disease development and progression of various dermatoses including atopic dermatitis, psoriasis, acne, hidradenitis suppurative, alopecia areata, vitiligo and skin malignancies (9).For example, increased abundance of staph aureus and reduced skin microbial diversity is seen in AD patients during exacerbations (10). Dysbiosis in other dermatoses include notable decrease in the abundance of Propionibacterium species and an increase in Staphylococcus and Streptococcus species in psoriasis, overgrowth of Malassezia sp. in seborrheic dermatitis, overgrowth of demodex mites in rosacea, different pathogenic strains of cutibacterium acnes in acne, reduction in corynebacterium and staph epidermididis in vitiligo, higher prevalence of Propionibacterium acnes and Staphylococcus species in alopecia and increase in staphylococcus aureus and streptococcus pyogenes in hidradenitis suppurative.Understanding how specific microbes interact with the host and contribute to disease pathogenesis is crucial for developing targeted interventions. Interventions targeted at modulating the skin microbiome composition or activity i.e probiotics, prebiotics and postbiotics may promise in managing skin conditions by restoring the microbial balance (11). Microbiome-derived biomarkers can guide the development of targeted drug therapies for better clinical outcomes and thus hold the potential for personalized treatment approaches. There’s a growing understanding of the skin-gut microbiota axis. Imbalances in one can affect the other, influencing immune responses and disease outcomes (12).16S rRNA sequencing is a widely used and highly sensitive method for analyzing microbial communities, including those on the skin. This technique targets the 16S ribosomal RNA gene, allowing precise identification and classification of microbial species. (13,14,15). Shotgun sequencing offers a comprehensive, high-resolution approach to studying microbial communities by sequencing the entire DNA content of a sample, rather than targeting specific regions like 16S rRNA. This method enables species- and strain-level identification, detects fungi, viruses, and archaea, and provides insights into functional genes, antibiotic resistance, and metabolic pathways. Unlike 16S sequencing, shotgun metagenomics allows for the analysis of host-microbe interactions, making it a powerful tool for understanding disease mechanisms, microbial dysbiosis, and potential therapeutic targets in conditions like atopic dermatitis.Overall, conducting studies on skin microbiome is essential in elucidating its role in health and disease, identifying potential therapeutic targets, and advancing dermatological research and personalised medicine initiatives.

Existing deficiency of current literature : There are only limited studies on skin microbiome analysis in patients with atopic dermatitis (AD), especially within the Indian population. Current research predominantly focuses on Western populations, which may not accurately represent the microbiome diversity seen in different ethnic groups. Studies like Kim et al. (2021) highlight the differences in skin microbiome composition across various ethnicities, underscoring the need for region-specific research (16).Additionally, there is a significant gap in understanding how regional and cultural factors influence the skin microbiome in AD patients from non- Western countries. For instance, Wang et al. (2021) indicated that geographic and lifestyle differences could lead to distinct microbial profiles in AD patients (17). The limited scope of current research fails to address these demographic variations, which could be crucial for developing targeted treatments.

Background / outcomes : Skin microbiome composition varies significantly based on race and ethnicity and despite known variations, there’s a scarcity of skin microbiome studies in Indian populations suggesting the need for region-specific research.Analyzing and comparing microbiome populations in diseased and non-diseased skin mayshed a deeper insight on understanding its role in disease pathogenesis and identifying therapeutic targets. Treatment using microbiome modulators, biomarkers and tailor-made approaches require understanding unique microbiome profiles in Indian AD patients. Understanding the alterations in the skin microbiome observed in patients with atopic dermatitis (AD) is crucial due to the significant impact of AD on patients’ quality of life.AD affects many individuals, causing persistent discomfort, itching, and psychological distress, significantly impairing their daily functioning and overall wellbeing.This research addresses a pressing clinical need to alleviate the suffering of AD patients.By gaining insights into the role of the skin microbiome in AD pathogenesis, we aim to develop personalized and innovative therapeutic strategies .These interventions can effectively improve clinical outcomes in the future.Establishing a solid evidence base that aims to enhance the standard of care for AD patients.