How Oral and Gut Microbes Shape Ulcerative Colitis
Imagine a universe within your body—a complex ecosystem of trillions of microorganisms that shape your health in ways we're only beginning to understand. For patients with ulcerative colitis (UC), a chronic inflammatory bowel disease, this internal universe may hold important clues to their condition. Recent groundbreaking research has focused on examining the oral and gut microbiomes of treatment-naïve UC patients—those who haven't yet undergone therapies that might alter their microbial communities 1 .
The human microbiome contains approximately 100 trillion microorganisms—outnumbering human cells by about 10 to 1!
What scientists are discovering challenges our understanding of UC and opens new possibilities for diagnosis and treatment. This article takes you on a journey through the latest discoveries about how these microscopic communities influence UC development and progression.
The significance of this research lies in its potential to revolutionize how we approach UC. Rather than simply managing symptoms, we might eventually target the root causes linked to microbial imbalances. By studying treatment-naïve patients, researchers can observe the microbiome in its most natural state—before medications, antibiotics, or other interventions alter its composition.
The gut microbiome refers to the vast collection of microorganisms that inhabit your gastrointestinal tract. In healthy individuals, these microbes exist in a balanced state, performing essential functions like aiding digestion, producing vitamins, training the immune system, and protecting against pathogens 8 .
The majority of gut bacteria belong to two main phyla: Firmicutes and Bacteroidetes, with smaller representations from Actinobacteria, Proteobacteria, and Verrucomicrobia.
While less discussed than its gut counterpart, the oral microbiome represents the second most diverse microbial community in the human body. It contains over 700 species of bacteria that inhabit various niches—teeth, gums, tongue, and cheeks 2 .
In a healthy state, these communities remain stable and contribute to oral health by preventing colonization by pathogenic species. Unlike the gut microbiome, which is largely shielded from external influences, the oral microbiome constantly interacts with the outside world.
Ulcerative colitis is a chronic inflammatory condition characterized by diffuse inflammation of the colon's innermost lining. Symptoms typically include abdominal pain, bloody diarrhea, urgency, and weight loss.
The disease often follows a relapsing-remitting pattern, with periods of symptom flare-ups alternating with periods of remission. While the exact cause remains unknown, it's believed to result from a complex interaction between genetic predisposition, environmental factors, and an abnormal immune response.
A particularly insightful study conducted in Saudi Arabia examined both mucosal and fecal microbiomes of 20 treatment-naïve pediatric UC patients, comparing them to non-IBD controls. The research team employed shotgun sequencing—a comprehensive method that sequences all genetic material in a sample—to achieve species-level discrimination of microorganisms 1 .
| Food Item | Control (%) | UC Patients (%) | Significance |
|---|---|---|---|
| Chicken (daily) | 60 | 15 | P = 0.0079 |
| Dairy (daily) | 85 | 50 | P = 0.0407 |
| Fruits (daily) | 5 | 35 | P = 0.0436 |
| Red meat (daily) | 10 | 25 | NS |
| Vegetables (daily) | 15 | 40 | NS |
Source: Saudi Arabian Study on treatment-naïve UC patients 1
The dietary comparisons revealed fascinating patterns: more control children (60%) ate chicken daily compared to the UC cohort (15%), while the UC cohort consumed more red meat, vegetables, and fruits on a daily basis. Researchers interpreted these findings as potentially indicating higher socioeconomic status in UC families, which aligns with previous epidemiologic studies linking increased family income and rapid dietary variation to pediatric IBD development 1 .
The concept of an oral-gut axis has gained considerable traction in recent years. This theory proposes that microorganisms from the oral cavity can translocate to the gastrointestinal tract, where they may influence gut health and disease. Under normal circumstances, stomach acid and other defense mechanisms prevent oral bacteria from colonizing the gut 2 .
Patients with UC frequently manifest dental problems including periodontitis, dental caries, oral ulcerations, halitosis, and oral lichen planus, suggesting a bidirectional relationship between oral health and intestinal inflammation 2 .
Once in the gut, these translocated oral bacteria may trigger immune responses or disrupt the delicate balance of the existing microbial community. Some oral pathogens are particularly adept at exploiting intestinal inflammation, using their specialized enzymes to degrade protective mucus layers and penetrate tissues.
| Bacterial Species | Association with UC | Proposed Mechanism |
|---|---|---|
| Porphyromonas gingivalis | Increased | Protease production, immune activation |
| Fusobacterium nucleatum | Increased | Adhesion molecules, inflammation promotion |
| Veillonella species | Enriched | Metabolic interactions with pathogens |
| Streptococcus species | Increased | May promote Th17 immune responses |
| Prevotella species | Depleted | Loss of potential beneficial functions |
Source: Research on oral microbiome alterations in UC patients 2
Research has demonstrated that patients with UC show distinct alterations in their oral microbiome composition. Studies have found decreased alpha diversity in UC patients compared to healthy controls, with increased abundance of Proteobacteria, Neisseriaceae, Staphylococcus, and Veillonella, alongside decreased levels of Peptostreptococcaceae and Lachnospiraceae 2 .
A groundbreaking study published in Nature Communications took microbiome research further by combining mucosal quantitative microbial profiling with host epigenomics, transcriptomics, and genotyping. This multi-omics approach provided unprecedented insights into how microbial and host factors interact to determine UC course 4 5 .
The research team developed a machine learning approach that combined microbiome and epigenome data to predict future relapse.
This combined model outperformed predictions based on any single data type alone, achieving impressive accuracy in identifying which children would experience disease flare within six months of diagnosis 4 5 .
| Bacterial Species | Association with Relapse | Proposed Functional Significance |
|---|---|---|
| Veillonella parvula | Increased | Pro-inflammatory effects, oral origin |
| Alloprevotella rava | Increased | Oral-associated, unknown function |
| Fusobacterium canifelinum | Increased | Periodontal pathogen, may promote inflammation |
| Faecalibacterium prausnitzii | Decreased | Butyrate producer, anti-inflammatory |
| Eubacterium rectale | Decreased | Butyrate producer, protective |
Source: Multi-omics study on UC relapse prediction 4 5
The study revealed that children who later experienced relapse had significantly lower bacterial diversity and richness at diagnosis compared to those who maintained remission. Specifically, relapsing children had fewer butyrate producers but more oral-associated bacteria 4 5 .
Of particular interest was the finding that Veillonella parvula—a Gram-negative anaerobic coccus commonly found in the oral cavity—was significantly increased in relapsing patients. Through subsequent experiments, the researchers demonstrated that this bacterium could induce pro-inflammatory responses in epithelial cell lines and colitis-prone mouse models 4 5 .
The growing understanding of microbiome alterations in UC has sparked development of novel therapeutic approaches aimed at restoring microbial balance. These innovative strategies represent promising avenues for future UC treatment.
Introducing beneficial microorganisms or substrates that encourage growth of beneficial native bacteria 8 .
Using viruses that specifically target pathogenic bacteria while sparing beneficial microbes 1 .
Developing targeted systems that restore microbial balance while reducing inflammation .
Microbiome research is also driving diagnostic advances. The development of a microbiome-based diagnostic test for IBD using metagenomic data from nearly 6,000 fecal samples represents a significant step forward. This test identified specific bacterial species that can distinguish UC and Crohn's disease from controls with high accuracy (AUC >0.90), maintaining performance across diverse ethnic groups 6 .
Similarly, the multiplex droplet digital PCR test targeting IBD-associated bacterial species showed numerically higher performance than fecal calprotectin—a current standard biomarker—in discriminating UC from controls. Such noninvasive diagnostic tools could eventually complement or even replace more invasive procedures like colonoscopy 6 .
The research on oral and gut microbiome profiles in treatment-naïve ulcerative colitis patients has revealed a complex interplay between our microbial inhabitants and intestinal health. What emerges is a story of ecological disruption—where decreased microbial diversity, depletion of beneficial butyrate producers, and invasion of oral-associated bacteria create an environment prone to inflammation.
The findings from these studies do more than just satisfy scientific curiosity; they pave the way for personalized medicine approaches in UC management. By understanding a patient's unique microbial profile, we might eventually predict disease course, select targeted therapies, and monitor treatment response with unprecedented precision.
Perhaps most importantly, this research underscores the interconnectedness of our bodily systems—demonstrating how oral health can influence gut inflammation and how microbial ecosystems spanning different body sites collectively contribute to health and disease. As we continue to unravel the complexities of the human microbiome, we move closer to transformative approaches for ulcerative colitis and other complex inflammatory conditions.
The hidden world within us remains largely unexplored territory, but with each study, we're mapping more of this fascinating landscape and discovering new opportunities to promote health and combat disease through intelligent manipulation of our internal microbial universe.