Inflammatory bowel disease (IBD) encompasses chronic inflammatory conditions of the gastrointestinal tract, primarily including Crohn’s disease (CD) and ulcerative colitis (UC). Both conditions significantly impact patient quality of life, morbidity, and the healthcare system. This overview provides a comprehensive look at the burden of IBD in the United States, highlighting differences between CD and UC, morbidity and mortality statistics, the evolution of treatments, and emerging research on the microbiome, adherent invasive E. coli (AIEC), and antimicrobial resistance.
IBD affects an estimated 1.6 million Americans, with about 780,000 individuals diagnosed with CD and another 907,000 with UC. The incidence of IBD has been increasing, with annual rates estimated at 12.3 per 100,000 person-years for CD and 12.8 per 100,000 person-years for UC.
IBD is associated with significant morbidity due to chronic inflammation, gastrointestinal symptoms, and extraintestinal manifestations. Symptoms include abdominal pain, diarrhea, rectal bleeding, weight loss, and fatigue. Patients often experience flares and periods of remission, affecting their ability to work, engage in daily activities, and maintain social relationships.
Crohn’s Disease (CD) can affect any part of the gastrointestinal tract from mouth to anus, often leading to complications such as strictures, fistulas, and abscesses. Ulcerative Colitis (UC) primarily affects the colon and rectum, leading to continuous mucosal inflammation and an increased risk of colorectal cancer.
While IBD is not typically fatal, it can lead to severe complications that increase mortality risk. Studies suggest that patients with CD have a slightly increased risk of mortality compared to the general population, primarily due to complications such as bowel perforation, infections, and malignancies. UC is associated with an increased risk of colorectal cancer, contributing to higher mortality rates among affected individuals.
IBD imposes a substantial economic burden on the US healthcare system. The annual direct medical costs for IBD are estimated to be between $14.6 and $31.6 billion. This includes hospitalizations, surgeries, medications, and outpatient care. Indirect costs, such as lost productivity and disability, further amplify the economic impact.
Patients with IBD frequently require medical interventions, including hospitalizations, surgeries, endoscopic procedures, and ongoing medical management. Hospitalization rates for IBD patients are significantly higher than those for the general population, with many patients requiring surgery at some point in their disease course.
Traditional treatments for IBD include aminosalicylates, corticosteroids, and immunomodulators such as azathioprine and methotrexate. While these therapies can induce and maintain remission, they are often associated with significant side effects and variable efficacy.
The advent of biologic therapies has revolutionized IBD treatment. Tumor necrosis factor (TNF) inhibitors, such as infliximab, adalimumab, and certolizumab, have shown significant efficacy in reducing inflammation and maintaining remission. Other biologics targeting different inflammatory pathways, such as vedolizumab (integrin inhibitor) and ustekinumab (IL-12/23 inhibitor), provide additional options for patients who do not respond to TNF inhibitors.
Recently, small molecule drugs such as Janus kinase (JAK) inhibitors (e.g., tofacitinib) have been developed for IBD treatment. These oral medications offer an alternative to biologics, targeting intracellular signaling pathways involved in inflammation.
Emerging research highlights the critical role of the gut microbiome in IBD pathogenesis. Dysbiosis, or an imbalance in the gut microbial community, is commonly observed in IBD patients. This imbalance can lead to a compromised intestinal barrier, increased mucosal inflammation, and altered immune responses. Therapeutic strategies aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), are being explored as potential treatments for IBD.
Adherent Invasive E. coli (AIEC) is a pathogenic strain of E. coli associated with CD. AIEC can adhere to and invade intestinal epithelial cells, survive and replicate within macrophages, and induce inflammatory responses. The presence of AIEC in the ileal mucosa of CD patients suggests a potential role in disease pathogenesis and persistence. Targeting AIEC through specific antibiotics, bacteriophages, or immune-modulating therapies is an area of active research.
The increasing rates of antimicrobial resistance complicate the treatment of IBD, particularly when managing infections or
IBD presents a significant burden in the United States due to its high prevalence, associated morbidity, and substantial economic impact on the healthcare system. The evolution of treatments from traditional therapies to targeted biologics and small molecules has improved patient outcomes, but challenges remain, particularly with the rise of antimicrobial resistance and the role of pathogenic bacteria like adherent invasive E. coli (AIEC). Ongoing research into the microbiome and innovative therapeutic strategies holds promise for better management and potential cures for IBD, ultimately aiming to reduce the overall burden of this chronic disease.
LBP-AIEC01 is a cocktail of engineered bacteriophages designed to precisely remove adherent-invasive E. coli in patients with IBDs. The rise of antibiotic resistance has led to a revival in the investigative and rescue use of bacteriophage (phage) therapy in patients with difficult-to-treat or life-threatening infections where there are frequently no alternative therapies. Locus has deployed a technology stack that provides a scale and capability set that has never been used in phage therapy, which is redefining the way engineered bacteriophages are used to treat disease.