Abstract Background First-degree relatives of IBD patients (FDRs) have compounded IBD risk in both the expression of various genetic risk loci and high exposure to environmental risk factors. Despite shared risk factors FDRs maintain their health status, eluding IBD diagnosis past the typical age of disease onset. Microbial changes in this unique cohort may provide insights into IBD relevant biomarkers of protection and/or risk. Methods PubMed and Embase repositories were searched for studies describing gastrointestinal microbial composition (Faecal or intestinal biopsies) in FDRs of IBD patients. Articles were systematically reviewed to elucidate a reliable microbial signature independent of study design and participant geography. Available 16S rRNA sequence datasets were downloaded and missing datasets requested along with relevant metadata. Integrated datasets were run through a unified QIIME2 pipeline followed by phyloseq and MaAsLin3. Results Our search strategy identified 4675 studies. Screening eliminated 4649 articles. Studies which met inclusion criteria (n = 26) underwent full text screening and data capture. Systematic review of primary data revealed consistent microbiome changes between FDRs and CD. Forest analysis revealed consistent reduced Shannon diversity in CD compared to FDR. Nine studies which provided microbial taxonomy information showed increases in Faecalibacterium, Roseburia and reduced Veillonella and gamma Proteobacteria in FDRs compared to CD. 4533 samples were included for reanalysis including 3946 FDRs, 177 healthy controls (HC) and 385 IBD patients. Unified reanalysis revealed consistently lower alpha diversity in IBD patients with comparable alpha diversities in HC and FDR groups. We identified conserved microbial patterns across datasets, suggesting that despite methodological and geographic variability, certain microbial shifts are reproducible and biologically meaningful. Compared to HC, FDRs had a depletion of protective genera Faecalibacterium and Agathobacter in favour of inflammatory genera such as Ruminococcus gnavus, Clostridium and Streptococcus. This suggests that the FDR microbiome has unique features compared to HC. Escherichia-Shigella, Veillonella, Ruminococcus gnavus and Haemophilus were consistently enriched in the IBD microbiome associated with pro-inflammatory responses and community instability. Despite these shared microbial features FDR signatures had significant abundance differences from IBD relatives more so than HC. Conclusion Our findings report unique microbial signatures in FDRs of IBD patients reinforcing the need for further in-depth research into IBD risk and microbial changes in this cohort. Conflict of interest: Ms. Koentgen, Sabrina: No conflict of interest Zhang, Fan: No conflict of interest Yip, Sophie: No conflict of interest Brooks, Ella: No conflict of interest Grimm, Michael Carl: No conflict of interest Hold, Georgina: No conflict of interest
Koentgen et al. (Thu,) studied this question.