P1322 Gut microbiome and Virome dynamics between rural and urban population suggests the severity in ulcerative colitis patients

Abstract Background Ulcerative colitis (UC) is chronic, inflammatory disease of the colon mucosa. Gut microbiome dysbiosis is considered to play a significant role in UC pathogenesis. Apart from bacteria, viruses are the intricate part of the gut microbiome which are often neglected in 16s rRNA based metagenomic studies. Therefore, whole genome sequencing (WGS) based studies of gut meta-DNA should be implemented to identify the microorganisms of different domains (bacteria, and viruses) residing in the human gut. Methods Human gut microbiota composition was assessed at microbiome and virome profiling using WGS of fecal samples. The gut metagenomes were further evaluated for the human gut resistome study. Results The UC gut was enriched with the pathobionts such as Escherichia coli and Bacteroides sp. The beneficial microbe resides in perfect mutualism in the gut such as Prevotella sp CAG_279, Firmicutes bacterium CAG_129, Ruminococcus torques (degradation of resistant starch) were lower in abundance in UC. The gut microbiota composition of urbanized population was more similar to UC as they have lower abundance of Firmicutes, Faecalibacterium prausnitzii and Oscillibacter sp 57_20. The lower prevalence of Ruminococcus torques, a keystone taxa in UC urban participants, indicates the loss of physiological functions. The UC patients exhibited a dysbiotic virobiota, characterized by increase in viral abundance, particularly from the genera enterovirus (observed in enteric gut infections), lentivirus (observed in chronic gut diseases), and Betacoronavirus. In UC patients, meta-gut resistome was found to be dominated by antimicrobial resistant genes (ARGs) compared to healthy. The metagenome study revealed a higher prevalence of ARG genes in the rural population (378 in Healthy; 607 in UC) compared to the urban (340 in Healthy; 578 in UC). The maximum number of observed ARGs corresponds to E. coli corroborates with the presence of a higher number of E. coli bacteriophages. Bacteriophages were reported as the important contributor for the dissemination of ARGs. Conclusion Our findings suggest inevitable evidence that specific alterations of microbes residing in the gut are associated with the lifestyle changes; therefore, can be used for screening the UC cases. The pro-inflammatory nature of microorganisms may contribute to UC severity in the intestinal tract. The observed rural and urban differences are unlikely an artifact of the difference between their lifestyles; urbanization is actively transforming the gut microbiota of local communities at the expense of loss and decline of microbes associated with traditional lifestyles. References 1.Banerjee, R., Pal, P., Patel, R., Godbole, S., Komawar, A., Mudigonda, S., ... & Travis, S. P. (2023). Inflammatory bowel disease (IBD) in rural and urban India: results from community colonoscopic evaluation of more than 30,000 symptomatic patients. The Lancet Regional Health-Southeast Asia, 2.Lloyd-Price, J., Arze, C., Ananthakrishnan, A. N., Schirmer, M., Avila-Pacheco, J., Poon, T. W., ... & Huttenhower, C. (2019). Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature, 569(7758), 655-662. 3.Yadav A, Shinde PB, Mohan H, Dhar MS, Ponnusamy K, Marwal R, Radhakrishnan VS, Goyal S, Kedia S, Ahuja V, Sharma KK. Gut colonization with antibiotic-resistant Escherichia coli pathobionts leads to disease severity in ulcerative colitis. Int J Antimicrob Agents. 2024 Oct;64(4):107289. doi: 10.1016/j.ijantimicag.2024.107289.