In this study, the investigators will explore our protein-based platform assessing commensals potentially contributing to features of CD, while assessing the global composition and abundance of AMPs expressed in the GI tract under specific CD-relevant clinical contexts. This would enable us to (a) identify new commensals contributing to features of CD spectrum and various sub-types; (b) uncover the mechanistic basis of dysbiosis in CD (c) utilize the pipeline to develop new theranostic for disease exacerbation, complication and treatment responses; and (d) potentially enable future exploitation of novel AMP combinations, and their respective antimicrobial capacity to counteract dysbiosis in CD.

Uncovering the proteomic manifestations of perturbed host-microbiome communications in CD will eventually enable the development and validation of clinical non-invasive surrogate markers, mechanistically determine causative drivers of CD, and potentially facilitate the development of novel therapeutic interventions.

Participants will be recruited from a community outpatient clinics and from a leading outpatient gastroenterology clinic: Emek Medical Center, after ICF signing , they will fill out a medical, demographic, and lifestyle habits questionnaires, as well as a food frequency questionnaire (FFQ). Participants will receive a home stool kit and will be instructed on how to use it. They will also receive a kit and an explanation regarding preparation materials for the colonoscopy. Subjects will be asked to collect stool samples at home - prior to colonoscopy and if possible - after colonoscopy bowel prep.

The seconed visit of the study will occure on the day of colonoscopy. Each patient will be clinically assessed by a gastroenterologist using the Crohn's Disease Activity Index (CDAI)30 and Harvey-Bradshaw Index (HBI); and collection of luminal, brush cytology, and mucosal samples from 4 different lower intestine regions

Inclusion criteria - CD study group:

• Age ≥ 18
• Candidates for a medically-indicated, diagnostic colonoscopy due to suspected new-onset CD.
• Naïve to any medical or nutritional intervention.

Inclusion criteria - healthy controls:

• Age- and gender-matched patients to the CD group, admitted for non-specific GI complaints (such as changes in bowel movements, bloating, abdominal pain) or routine screening for colorectal cancer as part of primary prevention per clinical guidelines.

Exclusion Criteria - both groups:

• Established diagnosis of inflammatory bowel disease (IBD) with prior treatment.
• Chronic gastro-intestinal disorder (e.g. celiac disease, eosinophilic esophagitis, collagenous gastritis, autoimmune gastritis, etc.).
• Type 1 or type 2 diabetes mellitus.
• Past or present history of malignancy.
• BMI > 30 (kg/m2)
• Use of systemic antibiotics or probiotics 2 months prior to enrolment.
• Use of steroids 2 months prior to enrolment (not including a short course of topical steroidal therapy).
• Any previous major gastric or intestinal surgery.
• Suspected or proven extensive involvement of non-ileal small intestine or colon, or significant perianal disease.
• Significantly stricturing or penetrating (fistulizing) disease at presentation.
• Chronic treatment with any oral/systemic immunosuppressive or anti-inflammatory drugs (e.g. steroids, 5-aminosalicylic acid, immunomodulators, biologics, etc.). Patients receiving these drugs as inhalers/creams/ointments should not be excluded from the study.
• Primary immunodeficiency.
• Pregnancy or breastfeeding in the last 6 months.
• Serious medical conditions that may alter the gut microbiome composition, based on investigators judgement (for example primary immunodeficiency, autoimmune disorder, or rheumatologic disease).

CD study group will consist of candidates for a medically-indicated, diagnostic colonoscopy due to suspected new-onset CD.

Naïve to any medical or nutritional intervention. for healthy controls: Age- and gender-matched patients to the CD group, admitted for non-specific GI complaints (such as changes in bowel movements, bloating, abdominal pain) or routine screening for colorectal cancer as part of primary prevention per clinical guidelines.