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BACKGROUND AND AIMS Case-control studies have shown that Crohn's disease (CD) patients have a different microbial composition than healthy individuals. Although the causes of CD are unknown, epidemiological studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. We hypothesized that long-term dietary clusters are associated with gut microbiome compositions as well as gut inflammation. Our objectives were to identify dietary patterns and assess if they are associated with alterations in specific gut microbial compositions and subclinical levels of gut inflammation in a cohort of healthy first-degree relatives (FDRs) of CD patients. METHODS As part of the Genetic, Environmental, Microbial (GEM) Project, we recruited a cohort of 2,289 healthy FDRs of CD patients. Individuals provided stool samples and answered a validated food frequency questionnaire (FFQ) reflecting their habitual diet over the year prior to sample collection. Unsupervised analysis identified three dietary and three microbial composition clusters. RESULTS one dietary cluster (DC3) resembling the Mediterranean diet was strongly associated with a defined microbial composition, with an increased abundance of fibre degrading bacteria such as Ruminococcus, as well as taxa such as Faecalibacterium. The DC3 diet was also significantly associated with lower levels of subclinical gut inflammation, defined by fecal calprotectin (FCP) as compared to other dietary patterns. There were no significant associations between individual food items and fecal calprotectin, suggesting that long term dietary patterns rather than individual food items contribute to subclinical gut inflammation. Additionally, mediation analysis demonstrated that DC3 had a direct effect on subclinical inflammation that was partially mediated by the microbiota. CONCLUSION Overall, these results indicated that Mediterranean-like dietary patterns are associated with microbiome and lower intestinal inflammation. This study will help guiding future dietary strategies that affect microbial composition and host gut inflammation to prevent diseases.