Gut microbiota in inflammatory bowel disease: a combined culturomics and metagenomics perspective

Abstract

Abstract Background: Gut dysbiosis has been linked to a variety of human diseases. Genome-based research has provided vast information on this topic over the past few decades, suggesting the necessity of microbial therapeutics. However, since genomic data alone are insufficient for experimental verification and clinical application of gut bacterial interactions, the need for culture-based gut microbiome research has been attracting great attention. Over the past decade, culturomics (a high-throughput cultivation and identification approach) has increased the possibility of overcoming this challenge. In our study, we explored the complementarity of culturomics and metagenomics by comparing the gut microbiota of healthy individuals with that of patients with ulcerative colitis (UC) and Crohn's disease (CD), which are subtypes of inflammatory bowel disease (IBD). Our ultimate goal was to select putative pathobionts related to each IBD subtype and probiotic candidates for microbiome-based therapeutics, which were extended from the metagenomics results. Results: We used a culturomics approach to obtain 14,131 gut bacterial isolates from UC and CD patients. They were classified into 265 species (UC, 215 and CD, 170). This IBD gut bacterial library included new species that had never been cultured. In the 16S rRNA gene amplicon sequence-based analysis, the gut dysbiosis in CD patients compared with the healthy control (HC) group was more severe than in UC patients compared with the HC group, with an increase in the abundance of Proteobacteriaand a decrease in the abundance of Actinobacteriota, which were dependent on the disease severity. Culturomics data also showed a more shifted dysbiosis in CD patients than in UC patients, with significantly decreasing species diversity, particularly anaerobes. From the two omics results, we suggested 24 taxa associated with UC or CD patients and 44 commensal species that could be used as live therapeutic candidates based on probiotic properties. Conclusions: Our study extended the understanding of gut dysbiosis in IBD patients using culturomic and metagenomic approaches. Our large-scale culture collection will be a foundation for identifying human gut bacterial diversity and strain characteristics.