Deciphering Salivary Microbiome Signature in Pediatric Inflammatory Bowel Disease

Introduction: Inflammatory bowel disease (IBD) is characterized by chronic gut inflammation and includes two conditions: Crohn's disease (CD) and ulcerative colitis (UC). While the precise causes of these diseases are not understood, microbial dysbiosis has been strongly implicated. Despite the known impact of the oral microbiome on gut health, research on the oral microbiome in pediatric IBD patients is limited. This study aims to investigate the salivary microbial communities in pediatric IBD patients (CD vs. UC) in the UAE, compare them with healthy controls (HC), and identify factors influencing these communities. Additionally, changes in the oral microbiome of IBD patients over time in response to treatment are examined. Methods: Seventy-eight participants were recruited, including 26 CD patients, 26 UC patients, and 26 HC over a one-year period. Salivary samples were collected from all participants, and DNA was extracted for 16S rRNA sequencing using Oxford Nanopore technology. Additionally, 20 patients were followed for 3-6 months to monitor changes in their oral microbiota during treatment. Results: The study confirmed significant dysbiosis in the salivary microbiome of IBD patients. Key microbial differences were noted at both the genus and species levels. Notable genus-level biomarkers included Veillonella, Prevotella, Brucella, Pelosinus, and Treponema. Species-level biomarkers included Veillonella parvula, Veillonella dispar, Prevotella denticola, Aerococcus urinae, and Haemophilus haemolyticus. These bacteria, often pathogenic, are associated with systemic inflammation and various infections, including IBD. IBD patients showed a significant reduction in alpha diversity, particularly in the CD group, and substantial differences in beta diversity across groups. Discussion: Factors influencing the oral microbiome were categorized into early life factors, general health factors, and IBD-related factors. Alpha diversity was significantly affected by factors such as mode of delivery, early feeding, age, BMI, high-fat diet, disease relapse, and IBD complications. Beta diversity was influenced by BMI, recent antibiotic use, IBD diet, disease duration, early feeding mode, and probiotic use. Longitudinal analysis showed dynamic shifts in microbiota biomarkers and diversity. The reduction or disappearance of certain Streptococcus species (e.g., Streptococcus pyogenes and Streptococcus agalactiae in CD) suggest responses to treatment and highlight the complex interactions within the oral microbiome. Conclusion: This study is the first in the UAE to investigate the oral microbiome in pediatric IBD patients, revealing significant microbial dysbiosis and identifying new microbial biomarkers. Utilizing high-resolution long-read sequencing provided detailed insights into the microbiome at the species level. Future research should include larger, more diverse cohorts and explore the impact of dietary and lifestyle changes on the oral and gut microbiome. Identifying factors that influence the microbiota, such as diet and antibiotic use, may help in preventing or mitigating IBD. Modulating the microbiota could be a potential strategy to restore a healthy microbiome and reduce gut inflammation in IBD patients.