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Facts: Inflammatory Bowel Disease
The gut microbiome, a complex ecosystem within our gastrointestinal tract, plays a pivotal role in health and disease.
What is IBD?
Inflammatory Bowel Disease (IBD) refers to a group of chronic inflammatory conditions in the gastrointestinal (GI) tract, with the two main types being Crohn’s Disease and Ulcerative Colitis. In IBD, the body’s immune system attacks the gut lining, leading to chronic inflammation. While the exact cause remains unknown, factors such as diet, environment, genetics, gut microbiome imbalances and immune dysfunction play a role.¹ Common symptoms include abdominal pain, diarrhea, weight loss and malnutrition, and fatigue. Those living with IBD experience flares, when symptoms are active, and remission periods, with few or no symptoms. Though, there is a common disconnect between symptoms and active inflammation, where even in remission periods, inflammation is often still present. Physicians are now trying to implement monitoring methods to be able to predict flares prior to the patient experiencing symptoms.
The Gut Microbiome & IBD
Individuals with IBD have a dysregulated gut microbiome, which generally shows a decreased diversity of bacterial species, with an increased abundance of harmful bacteria and a lack of beneficial bacteria. Many of these microbes have shown to play a role in either driving or suppressing inflammation, which has recently prompted researchers to explore methods to predict the patient’s responsiveness to different therapies, based on the microbes in their gut.² Furthermore, microbiome-based therapies are a promising new approach for treatment, and at Melius MicroBiomics, we aim to be industry leaders in this new field of therapy.
Crohn’s Disease vs. Ulcerative Colitis
Crohn’s Disease and Ulcerative Colitis are the primary types of IBD, but with distinct characteristics:
Feature | Crohn’s Disease | Ulcerative Colitis |
|---|---|---|
Location | Inflammation in patches (skip lesions) | Inflammation is continuous |
Inflammation Pattern | Throughout any part of the GI tract (mainly in small intestine & colon) | Localized in the colon and rectum |
Damage | Deep into intestinal tissue – can lead to abscesses or fistulas | Affects only the innermost lining |
Symptoms | Abdominal pain, weight loss, mouth ulcers, diarrhea, fistulas | Bloody stool, urgency, abdominal cramping, diarrhea, weight loss |
Feature | Crohn’s Disease | Ulcerative Colitis |
|---|---|---|
Location | Inflammation in patches (skip lesions) | Inflammation is continuous |
Inflammation Pattern | Throughout any part of the GI tract (mainly in small intestine & colon) | Localized in the colon and rectum |
Damage | Deep into intestinal tissue – can lead to abscesses or fistulas | Affects only the innermost lining |
Symptoms | Abdominal pain, weight loss, mouth ulcers, diarrhea, fistulas | Bloody stool, urgency, abdominal cramping, diarrhea, weight loss |
Feature | Crohn’s Disease | Ulcerative Colitis |
|---|---|---|
Location | Inflammation in patches (skip lesions) | Inflammation is continuous |
Inflammation Pattern | Throughout any part of the GI tract (mainly in small intestine & colon) | Localized in the colon and rectum |
Damage | Deep into intestinal tissue – can lead to abscesses or fistulas | Affects only the innermost lining |
Symptoms | Abdominal pain, weight loss, mouth ulcers, diarrhea, fistulas | Bloody stool, urgency, abdominal cramping, diarrhea, weight loss |
Managing IBD: Diet & Lifestyle
Emerging evidence continues to reveal that lifestyle and dietary modifications can significantly impact IBD symptoms. The Mediterranean diet has received a lot of attention as an approach to help manage IBD, as it is shown to improve microbial diversity and reduce intestinal inflammation. The Mediterranean diet includes microbiota-accessible carbohydrates, omega-3 fatty acids, polyphenols and antioxidants, which are all important aspects for gut health.⁵ While the Mediterranean diet itself serves as a useful tool for IBD patients, there are other diets that may serve useful – the important takeaway from this beneficial diet is that it is dense in nutrients, high in fiber and healthy fats, and low in ultra-processed foods.
To learn more about different dietary practices with IBD, click here.
Current IBD Treatments
Though there is no cure for IBD, several treatment options can help manage symptoms. The treatment landscape follows a stepwise approach, based on disease severity. While many treatments are available, they are not optimal, as many patients lose responsiveness overtime. This lack in efficacy, along with the side effects that come with many of these treatments, drive the need for the many drugs available and in development.³
Below presents the treatment pyramid for IBD. Based on the patient’s severity and response to therapies, physicians will take a stepwise approach, leading to more intensive interventions as you move up the pyramid. Typically, patients with moderate-to-mild ulcerative colitis start on the frontline treatment, 5-aminosalicylic acid (5-ASA). There are few drugs available at the base phase for treatment, often leading to patients requiring more intensive drugs. Melius aims to address this unmet need, with the potential to replace 5-ASA as the frontline therapy with our BioPersist product.
The table below provides an overview of the drugs presented in the IBD treatment pyramid, highlighting their mechanism of action, efficacy, limitations and side effects. Several unwanted side effects come with majority of this treatments such as suppressing the immune system, increased risk of infection, nausea, and worsening pre-existing conditions.
Drug Class | Examples | Administration | Mechanism of Action | Efficacy & Limitations | Side Effects |
|---|---|---|---|---|---|
5-ASA | Mesalazine/Asacol® Olsalazine/Dipentum® Balsalazide/Colazide® | Oral, enema, suppository, or foam | Inhibits inflammation through multiple proposed mechanisms | Often used for mild-to-moderate ulcerative colitis. A systematic review of 54 RCTs showed 71% of patients failed to reach clinical remission.⁴ | Headache, nausea, abdominal pain/cramping, vomiting, appetite loss, rash, or fever |
Antibiotics | Metronidazole/Flagyl® Ciprofloxacin/Cipro® Vancomycin/Vancocin® Rifaximin/Xifaxan® | Oral or intravenous | Treat infections related to IBD complications or medications (e.g., Clostridium difficile infections) | Useful for short-term infections but not suitable for long-term use due to risks of antimicrobial resistance. | Increased antimicrobial resistance, nausea, vomiting, loss of appetite, diarrhea, rash |
Steroids | Methylprednisolone (Solumedrol®) Prednisone (Deltasone®) Budesonide (Entocort®, Cortiment®) Hydrocortisone | Intravenous, oral, or rectal | Broad immunosuppressive effects by mimicking adrenal gland hormones (glucocorticoids) | Used short-term for moderate-to-severe disease due to significant side effects, not recommended for long-term management. | Acne, weight gain, bruising, stretch marks, fluid retention, depression, psychosis, osteoporosis, steroid myopathy, increased infection risk, diabetes, hypertension, growth retardation |
Immunosupp-ressants | Thiopurines Methotrexate/MTX® | Oral or injection | Suppress immune response through various mechanisms; often combined with biologics to enhance efficacy | Require close monitoring due to potential side effects. Not all are effective for ulcerative colitis but can improve outcomes when used in combination therapies. | Nausea, increased risk of infection, liver complications, bone marrow suppression, lung inflammation, contraindicated in pregnancy |
Biologics & Biosimilars | Anti-TNF-α Infliximab/Remicade® Adalimumab/Humira® Golimumab/Simponi® Anti-integrin Vedolizumab/Entyvio® Anti-IL 12/23 Ustekinumab/Stelara® | Intravenous infusion or subcutaneous injection | Biologics (e.g., monoclonal antibodies) bind and inactivate cytokines driving inflammation
Biosimilars are highly similar copies of biologics | Effective but very costly, with risk of anti-drug antibodies.
Biosimilars reduce costs but must prove no significant difference in safety and efficacy from originals. | Increased risk of infection, infusion reactions, headache, fever, rash, severe allergic reactions, increased cancer risk (low), can worsen MS, lupus, and heart failure |
Small Molecule Drugs | JAK inhibitors Upadacitinib, Tofacitinib | Oral | Janus Kinase (JAK) inhibitors reduce inflammation by targeting intracellular signaling pathways | Effective but associated with more side effects, as they are less targeted compared to biologics. | Increased cholesterol, increased cancer risk, infection, blood clots, cardiac events, death |
Surgery | Colectomy, ileal pouch-anal anastomosis (IPAA), ostomy procedures | Surgical intervention | Physically removes diseased portions of the bowel to alleviate symptoms and prevent further complications | Often considered when medications fail or complications like severe bleeding, perforation, or cancer risk occur. Not a cure for Crohn’s disease but can be curative for ulcerative colitis. | Risks of infection, bleeding, bowel obstruction, nutritional deficiencies, and changes in bowel habits post-surgery |
Drug Class | Examples | Administration | Mechanism of Action | Efficacy & Limitations | Side Effects |
|---|---|---|---|---|---|
5-ASA | Mesalazine/Asacol® , Olsalazine/Dipentum® , Balsalazide/Colazide® | Oral, enema, suppository, or foam | Inhibits inflammation through multiple proposed mechanisms | Often used for mild-to-moderate ulcerative colitis. A systematic review of 54 RCTs showed 71% of patients failed to reach clinical remission.⁴ | Headache, nausea, abdominal pain/cramping, vomiting, appetite loss, rash, or fever |
Antibiotics | Metronidazole/Flagyl® , Ciprofloxacin/Cipro® , Vancomycin/Vancocin® , Rifaximin/Xifaxan® | Oral or intravenous | Treat infections related to IBD complications or medications (e.g., Clostridium difficile infections) | Useful for short-term infections but not suitable for long-term use due to risks of antimicrobial resistance. | Increased antimicrobial resistance, nausea, vomiting, loss of appetite, diarrhea, rash |
Steroids | Methylprednisolone (Solumedrol®), Prednisone (Deltasone®), Budesonide (Entocort®, Cortiment®), Hydrocortisone | Intravenous, oral, or rectal | Broad immunosuppressive effects by mimicking adrenal gland hormones (glucocorticoids) | Used short-term for moderate-to-severe disease due to significant side effects, not recommended for long-term management. | Acne, weight gain, bruising, stretch marks, fluid retention, depression, psychosis, osteoporosis, steroid myopathy, increased infection risk, diabetes, hypertension, growth retardation |
Immunosupp-ressants | Thiopurines, Methotrexate/MTX® | Oral or injection | Suppress immune response through various mechanisms; often combined with biologics to enhance efficacy | Require close monitoring due to potential side effects. Not all are effective for ulcerative colitis but can improve outcomes when used in combination therapies. | Nausea, increased risk of infection, liver complications, bone marrow suppression, lung inflammation, contraindicated in pregnancy |
Biologics & Biosimilars | Anti-TNF-α: Infliximab/Remicade® , Adalimumab/Humira® , Golimumab/Simponi®
Anti-integrin: Vedolizumab/Entyvio®
Anti-IL 12/23 : Ustekinumab/Stelara® | Intravenous infusion or subcutaneous injection | Biologics (e.g., monoclonal antibodies) bind and inactivate cytokines driving inflammation
Biosimilars are highly similar copies of biologics | Effective but very costly, with risk of anti-drug antibodies.
Biosimilars reduce costs but must prove no significant difference in safety and efficacy from originals. | Increased risk of infection, infusion reactions, headache, fever, rash, severe allergic reactions, increased cancer risk (low), can worsen MS, lupus, and heart failure |
Small Molecule Drugs | JAK inhibitors: Upadacitinib, Tofacitinib | Oral | Janus Kinase (JAK) inhibitors reduce inflammation by targeting intracellular signaling pathways | Effective but associated with more side effects, as they are less targeted compared to biologics. | Increased cholesterol, increased cancer risk, infection, blood clots, cardiac events, death |
Surgery | Colectomy, ileal pouch-anal anastomosis (IPAA), ostomy procedures | Surgical intervention | Physically removes diseased portions of the bowel to alleviate symptoms and prevent further complications | Often considered when medications fail or complications like severe bleeding, perforation, or cancer risk occur. Not a cure for Crohn’s disease but can be curative for ulcerative colitis. | Risks of infection, bleeding, bowel obstruction, nutritional deficiencies, and changes in bowel habits post-surgery |
Key Terms to Know
Crohn’s Disease: a type of IBD, characterized by chronic inflammation in any part of the gastrointestinal tract. Inflammation presents in patches (skip lesions) and damage to tissue can penetrate deep into the intestinal wall, which can lead to fistulas and strictures.
Ulcerative Colitis: a type of IBD, characterized by chronic inflammation in the colon (large intestine) or rectum. Inflammation presents in continuous pattern, starting from the rectum, and affects only the innermost layer of the intestinal wall.
Flares: period of active disease, where IBD symptoms worsen. Flares can be triggered by various factors such as stress, diet, infections, or medication changes.
Remission: period of minimal or no symptoms. Remission can be achieved through medications and microbiome-based therapies, diet, and lifestyle changes.
Resources
If you are living with IBD or simply want to learn more, we have compiled the following helpful resources:
Do you have IBD and are on a medication that you would like to learn more about? Search your medication here to learn more.
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