This study investigates the long-term dynamics of the gut microbiome in patients with Inflammatory Bowel Disease (IBD), including ulcerative colitis (UC), Crohn’s Disease (CCD), and ileal CD (ICD). The researchers collected fecal samples from 128 IBD patients and 9 healthy controls at three-month intervals over a two-year period, totaling 683 samples. They used 16S rRNA gene sequencing to analyze microbial composition and correlated these findings with clinical data, including fecal calprotectin concentrations and surgical resection status. Key findings include: - IBD microbiomes showed greater volatility compared to healthy individuals, deviating more from a newly defined "healthy plane" (HP) that represents normal microbial variation. - ICD patients, especially those who had undergone ileocecal resection, deviated the most from the HP. - Some IBD patients periodically visited the HP but then deviated away, suggesting periods of remission and relapse. - Fecal calprotectin concentrations were higher in all IBD subtypes but were not significantly correlated with distance from the HP. - Medication changes, particularly corticosteroid use, influenced microbiome volatility. - A Random Forests model using microbial and clinical data accurately predicted IBD subtypes, with the HP being a critical factor. The study highlights the dynamic nature of the gut microbiome in IBD and suggests that maintaining the microbiome in a healthy state may be crucial for managing the disease.This study investigates the long-term dynamics of the gut microbiome in patients with Inflammatory Bowel Disease (IBD), including ulcerative colitis (UC), Crohn’s Disease (CCD), and ileal CD (ICD). The researchers collected fecal samples from 128 IBD patients and 9 healthy controls at three-month intervals over a two-year period, totaling 683 samples. They used 16S rRNA gene sequencing to analyze microbial composition and correlated these findings with clinical data, including fecal calprotectin concentrations and surgical resection status. Key findings include: - IBD microbiomes showed greater volatility compared to healthy individuals, deviating more from a newly defined "healthy plane" (HP) that represents normal microbial variation. - ICD patients, especially those who had undergone ileocecal resection, deviated the most from the HP. - Some IBD patients periodically visited the HP but then deviated away, suggesting periods of remission and relapse. - Fecal calprotectin concentrations were higher in all IBD subtypes but were not significantly correlated with distance from the HP. - Medication changes, particularly corticosteroid use, influenced microbiome volatility. - A Random Forests model using microbial and clinical data accurately predicted IBD subtypes, with the HP being a critical factor. The study highlights the dynamic nature of the gut microbiome in IBD and suggests that maintaining the microbiome in a healthy state may be crucial for managing the disease.