Background: Atopic dermatitis (AD) is a chronic inflam-matory skin disease characterized by recurrent eczematous skin lesions and intense itching. Worldwide, it affects 10-30% of children and 2-10% of adults, with a two- to three-fold increase in prevalence observed over the last several decades. Recent advances in sequencing technology have demonstrated that the development of AD not only associate with the skin microbi-ome but gut microbiota. Gut microbiota plays an important role in allergic diseases including AD. The hypothesis of the “gut-skin" axis has been proposed and the cross-talk mechanism be-tween them has been gradually demonstrated in the researches. Aim of Study: The aim of this work is to identify the specif-ic patterns of gut microbiome in moderate and severe clinical severities of atopic dermatitis inpatients >3 years old. Patients and Methods: Randomized-controlled study was carried out on 20 patients >2 years old with moderate to se-vere AD assessed by SCORAD index in addition to a control group of 20 healthy subjects without personal or family history of any atopic diseases to identify the specific patterns of gut microbiome in moderate and severe clinical severities of AD at Dermatology Clinic at Menoufia University Hospitals from March 2022 to May 2023. Results: There were no statistically significant differenc-es between severe and moderate forms of disease as regards age (p=0.077) and age of onset (p=0.482). While, there was a highly statistically significant difference between moderate and severe cases as regards duration of disease in years (p=0.005). There was a high statistically significant difference be-tween different study groups as regards alpha diversity of the gut microbiome (p<0.01). There was no significant correlation between alpha diver-sity of gut microbiome and age of onset, duration, severity and sites of disease lesions. Conclusion: Our study suggests that gut microbiota in patients with AD showed lower alpha diversity than healthy control subjects and supports the hypothesis that low microbial diversity is associated with an increased risk for allergic disease as AD. Recommendations: There is a need for a profound under-standing of the interactive mechanism between intestinal mi-crobiota and host immune system. Large cohort study to detect the specific role of micro organisms in the pathogenesis and development of AD.