Table of contents

What is Crohn’s disease?

Crohn’s disease is a type of inflammatory bowel disease (IBD) that can cause abdominal pain, severe diarrhea, chronic fatigue, weight loss, and malnutrition. Inflammation may affect various parts of the digestive tract (most commonly the terminal section of the small intestine or the colon) and can even extend into the deeper layers of the intestinal wall.

This disease can be extremely painful and negatively impact quality of life. In more severe cases, life-threatening complications may occur.

Researchers still do not fully understand the causes of Crohn’s disease, who is most at risk, or the most effective treatment. Despite significant advancements in recent decades, there is currently no cure. Therefore, further research is needed.

Although there is no known cure, various therapies can reduce symptoms and even lead to long-term remission and healing of inflammation. With appropriate treatment, patients’ quality of life can be significantly improved. [1]

The functional medicine approach to Crohn’s disease involves identifying and addressing the underlying causes of inflammation by supporting the body’s natural healing processes. Functional or integrative medicine practitioners may use tests for food intolerances, stool analysis, and other individualized diagnostics. These tests help practitioners and patients identify the root cause of inflammation and develop a personalized treatment plan and diet.

What are the symptoms of Crohn’s disease?

Many individuals with Crohn’s disease experience symptoms for years before receiving an official diagnosis [2]. Symptoms most commonly begin during the teenage years or twenties, though the disease can occur at any age [3]. Crohn’s disease typically follows a fluctuating course, alternating between flare-ups and periods of remission. [4]

Symptoms usually develop gradually, though a sudden onset is possible in rare cases. Certain symptoms may worsen over time. Common early symptoms include [5]:

• diarrhea
• abdominal cramps
• bloody stools
• fever
• fatigue
• loss of appetite
• weight loss
• a feeling of fullness after bowel movements
• frequent urge to defecate

These symptoms can often be mistaken for food poisoning, digestive upset, or allergies.

Figure 1. The earliest symptoms of Crohn’s disease may include abdominal pain, constipation, stomach cramps, weight loss, fever, and fatigue

Abdominal pain is one of the most common early signs of Crohn’s disease [6], especially in the lower right abdomen. In severe cases, patients may have more than 20 bowel movements daily and frequently wake up at night to defecate [3], [6–8]. Bloody stools may also occur, typically intermittently, and may appear light or dark red. In advanced stages, significant bleeding may occur. [9]

As the disease progresses, symptoms may intensify, including [5]:

• rectal fistulas
• ulcers (anywhere from mouth to anus)
• joint and skin inflammation
• shortness of breath or limited mobility due to anemia

Early detection can help prevent serious complications and allow for timely treatment.

Crohn’s disease can also cause symptoms outside the intestinal tract, including [10]:

• eyes (redness, pain, visual disturbances)
• mouth (sores)
• joints (pain and swelling)
• skin (lumps, ulcers, sores, rashes)
• bones (osteoporosis)
• kidneys (kidney stones)
• liver (primary sclerosing cholangitis and cirrhosis – rare)

Figure 2. Symptoms associated with Crohn’s disease can also appear outside the intestinal tract, affecting other parts of the body

Symptoms occurring outside the digestive tract are known as extraintestinal manifestations. For some, these symptoms appear years before intestinal symptoms, while in others, they coincide with flare-ups.

Complications of Crohn’s disease

Complications may include intestinal obstruction, abscesses, perforation, and bleeding, which can be life-threatening.

Crohn’s disease can affect organs beyond the digestive tract [11]. One common eye-related complication is uveitis, which can cause blurred vision and eye pain [12]. If untreated, it may lead to blindness [11]. Inflammation can develop in both the conjunctiva and the sclera, which can lead to scleritis or episcleritis. [12]

Crohn’s disease is linked to a rheumatic condition called seronegative spondyloarthritis, which is marked by joint inflammation (arthritis) or inflammation at tendon attachment points (enthesitis). [12]

Other affected systems include the skin, blood, and endocrine systems. The most common skin condition is erythema nodosum, affecting around 8% of patients. It causes painful red lumps, mostly on the legs [12–14]. A rarer but more severe skin condition is pyoderma gangrenosum, which affects fewer than 2% of patients and is characterized by painful, ulcerated nodules. [11], [14]

Crohn’s disease also raises the risk of blood clots [12]. Leg pain and swelling may signal deep vein thrombosis, while sudden shortness of breath could indicate a pulmonary embolism.

Neurological complications occur in up to 15% of patients, including seizures, stroke, muscle disorders (myopathy), peripheral neuropathy, headaches, and depression. [15]

Due to ongoing inflammation, Crohn’s disease may increase cancer risk. Involvement of the small intestine is associated with a higher risk of small bowel cancer [16], while colon involvement increases colon cancer risk. [17]

Crohn’s disease frequently causes anemia, which may stem from deficiencies in vitamin B12, folate, or iron, or from chronic inflammation [18–19]. The disease often affects the terminal ileum, where vitamin B12 is absorbed [18], explaining why deficiency is especially common after surgical removal of this segment. [19]

What causes Crohn’s disease?

Although the exact causes are unknown, Crohn’s disease likely results from a combination of genetic, immune, microbial, and environmental factors in genetically predisposed individuals [6], [20–22]. Therefore, the causes listed below—genetics, immune system factors, pathogens, and environmental influences—may all contribute to the development of the disease. No single factor has been identified as the sole cause.

Genetics

Crohn’s disease is thought to arise from genetic susceptibility combined with environmental triggers [23]. It is the first genetically complex disease in which links between genetic factors and the immune system have been extensively studied [24]. Over 70 genes have been associated with Crohn’s, with genetics accounting for about half the overall risk. [3], [25]

Genomic studies show genetic overlap between IBD and celiac disease [26]. Crohn’s is also linked to the LRRK2 gene, which is associated with Parkinson’s disease. [27]

Immune system

Crohn’s disease is widely considered an autoimmune condition. Some theories, however, propose defects in the innate immune system [28]. One hypothesis suggests that macrophage dysfunction impairs cytokine secretion, triggering chronic microbial inflammation [21], [29]. Another proposes that inflammation results from excessive Th1 and Th17 immune responses. [30–31]

One theory posits that the immune system evolved in the presence of parasites; with modern hygiene, reduced exposure may weaken immune regulation. In one study, 23 out of 29 Crohn’s patients exposed to harmless parasites experienced symptom improvement, with 21 achieving remission. [32]

Pathogens

Although the exact causes of Crohn’s disease remain unknown, a growing body of research suggests that, in addition to genetic predisposition, various microorganisms—including pathogens—may play a role in the development of the condition. Current theories propose that Crohn’s disease arises in individuals who develop an abnormal immune response to the intestinal microbiota [33]. This immune dysregulation may be triggered by a prior infection, such as gastroenteritis, or by a disturbance in microbial balance (homeostasis), known as dysbiosis. [3]

Other Microorganisms

Beyond intestinal bacteria, several other microorganisms have been identified as potential independent pathogenic contributors. Current evidence points to Mycobacterium avium subspecies paratuberculosis (MAP), specific E. colistrains (e.g., AIEC), Epstein–Barr virus (EBV), Candida tropicalis, and Clostridioides difficile as possible culprits. These pathogens may directly damage the intestinal mucosa and stimulate inappropriate or excessive immune responses, thereby playing a role in both the development and chronic persistence of Crohn’s disease.

Mycobacterium avium subspecies paratuberculosis (MAP)

MAP causes Johne’s disease in the intestines of cattle. Since Johne’s disease shares similarities with Crohn’s disease, it is believed that this bacterium may also play a role in Crohn’s disease. Several studies have investigated the involvement of MAP in the development of Crohn’s disease. [40–41]

The eradication of MAP is also being explored as a therapeutic approach [42]. For instance, antibiotic treatment targeting MAP has been studied. Although the results remain inconclusive, antibiotic use is generally considered to be beneficial. [43–44]

Escherichia coli

Since adherent-invasive Escherichia coli (AIEC) is more common in individuals with Crohn’s disease, specific strains of AIEC have been linked to the disease [37], [45–46]. These bacteria are capable of forming stronger biofilms than non-adherent-invasive E. coli strains. [47–48]

Epstein-Barr virus

The Epstein-Barr virus is closely associated with several intestinal diseases. In addition to Crohn’s disease, it has been linked to ulcerative colitis, peptic ulcer disease, acute appendicitis, and stomach cancer.

The virus is not detected in healthy gastrointestinal mucosa but is present in 55% to 63% of intestinal tissue samples from individuals with Crohn’s disease. [49–50]

A particular concern is that Epstein-Barr virus can remain dormant until reactivated by immunosuppressive drugs, such as steroids [51]. Consequently, these medications may further exacerbate Crohn’s disease. [52]

Candida tropicalis

A 2016 study published in the American Society for Microbiology journal reported an increased incidence of Candida tropicalis in the stool of patients with Crohn’s disease. High levels of this fungus were also found alongside antibodies to Saccharomyces cerevisiae, providing a means to distinguish Crohn’s disease from ulcerative colitis.

These fungi were discovered together with two bacteria, Escherichia coli and Serratia marcescens. Together, the fungus and the two bacteria formed a thick, large biofilm. These biofilms contributed to the dysbiosis of the intestinal flora in Crohn’s disease. This study was the first to demonstrate that fungi may also play a causative role in Crohn’s disease, whereas previously only bacteria and viruses were suspected. [33]

Clostridioides difficile

Clostridium difficile is a common inhabitant of the intestinal tract, with several strains differing in their pathogenicity. Its presence does not necessarily indicate disease. Antibiotic treatment often disrupts the intestinal flora, which can lead to diarrhea and Clostridium difficile infection. [53]

Clostridium infection also plays a significant role in inflammatory bowel disease. [54]

Clostridium difficile is a common hospital-acquired infection, with mortality rates ranging from 8% to 37.2% according to research [55]. The risk of infection was reduced by 50% when probiotics were administered simultaneously with antibiotics. [56]

Environmental influences

Crohn’s is more prevalent in Western countries [57], affecting 3.2 per 1,000 people in Europe and North America [58], but is rarer in Asia and Africa. [58–59]

It typically begins in adolescence or early adulthood [3], [6], [60], and affects both sexes equally. [6]

Crohn’s is linked to high intake of animal and dairy proteins and an increased ratio of omega-6 to omega-3 polyunsaturated fatty acids. It is less common among people who consume plant proteins. Fish protein shows no effect. [61]

Among smokers, the risk of developing Crohn’s disease is twice as high compared to non-smokers. Moreover, smoking further increases the risk of relapse and flare-ups in those already diagnosed with the disease. [62]

The introduction of hormonal contraception in the United States during the 1960s coincided with a significant increase in the incidence of Crohn’s disease. One hypothesis suggests that these drugs affect the digestive system in a manner similar to smoking [58]. Chronic stress is also believed to exacerbate the disease, although concrete evidence supporting this is lacking. [6]

Risk factors

The following factors may contribute to the onset of Crohn’s disease [1]:

• Age: Although Crohn’s can develop at any age, it most commonly begins in young adulthood. Most people are diagnosed before age 30.
• Ethnicity: While Crohn’s can affect any ethnic group, it is most common among Caucasians.
• Genetics: Individuals with a first-degree relative (parent, sibling, or child) who has Crohn’s disease have a significantly higher risk. About 20% of those with Crohn’s have a family member with the disease.
• Smoking: Quitting smoking is the most effective modifiable risk factor for preventing Crohn’s disease.
• Anti-inflammatory drugs: Although nonsteroidal anti-inflammatory drugs (NSAIDs) do not cause Crohn’s, they may contribute to intestinal inflammation and worsen the condition.

Figure 3. Risk factors for Crohn’s disease may include age, genetic factors, ethnicity, and smoking

Diagnosis of Crohn’s disease

Diagnosing Crohn’s disease is challenging [2]. Multiple tests are often required, and even then, a definitive diagnosis may not be possible. [60]

Diagnosis should be based on medical history, physical examination, imaging, and laboratory test results. It is crucial to distinguish Crohn’s disease from similar conditions such as irritable bowel syndrome (IBS), Behçet’s disease, or infectious diseases like yersiniosis and enteroviruses. Endemic diseases like tuberculosis must also be ruled out. [3]

The following diagnostic tools may be used to confirm Crohn’s, differentiate it from other conditions, like IBS and ulcerative colitis and exclude other causes [3]:

• Medical history, including a detailed family medical history, is essential. Attention should be given to factors such as the onset time of symptoms, recent travel, presence of blood and/or mucus in the stool, cramps, nighttime diarrhea, eating habits, recent intestinal infections, use of non-steroidal anti-inflammatory drugs, history of appendectomy, and recent episodes of gastroenteritis. Additionally, screening for symptoms outside the intestinal tract is necessary.
• Physical examination: Includes pulse, blood pressure, weight, BMI, abdominal and perianal examination, digital rectal exam, and checking for extraintestinal signs.
• Microbiological tests: Stool analysis and testing for Clostridium difficile.
• Pathological and histological analysis: At least two biopsies from five intestinal segments, including the ileum.
• Gastroscopy
• Colonoscopy
• Small bowel endoscopy
• X-ray
• CT scan
• MRI
• Capsule endoscopy
• Laboratory tests: Complete blood count, erythrocyte sedimentation rate, C-reactive protein, liver function, electrolytes, and antibody screening (ASCA = yeast antibodies, ANCA = antineutrophil cytoplasmic antibodies).
• Patients with suspected or confirmed extraintestinal symptoms should also consult specialists such as surgeons, rheumatologists, dermatologists, ophthalmologists, urologists, or gynecologists (if a rectovaginal fistula is suspected).

What foods cause symptoms?

Food and drink do not cause inflammatory bowel disease, but they can aggravate symptoms, especially during flare-ups. [1]

Keeping a food diary can help patients identify which foods trigger symptoms, allowing them to adjust their diet accordingly.

Many patients find that reducing or eliminating dairy helps ease diarrhea, abdominal pain, and gas. Lactose intolerance may be present, and milk protein may also contribute to symptoms. Avoiding casein (a protein found in cow’s milk) and possibly gluten may also be beneficial. [64]

Diets rich in fiber and fruits are associated with reduced Crohn’s risk, while diets high in fats, polyunsaturated fatty acids such as omega-6, and meat may increase risk.

During flare-ups, a low-fiber diet may help manage acute symptoms. [65]

How can Crohn’s disease be treated?

There is currently no cure or surgical treatment that can eliminate Crohn’s disease [3], [6]. The goal of treatment is to reduce inflammation, relieve symptoms (pain, diarrhea, bleeding), and correct nutritional deficiencies. [66]

Treatment may involve medication, dietary supplements, surgery, or a combination of these, depending on the disease stage, severity, complications, and prior treatment responses.

Several medications are used to treat Crohn’s disease. These include anti-inflammatory drugs such as corticosteroids, antibiotics, and anti-diarrheal medications. Immunosuppressive drugs like methotrexate or azathioprine may also be prescribed. Various painkillers can be used to alleviate pain. In more severe cases, biological therapy may be employed.

Surgery can be performed to address complications of Crohn’s disease, including fistulas, small bowel obstruction, colon cancer, small bowel cancer, and intestinal blockages. Surgery is also necessary if a segment of the intestine no longer responds to medication [67]. However, surgery does not cure or eliminate Crohn’s disease itself. [68]

Fatigue may be managed with regular exercise, a nutritious diet, and proper sleep. Smoking can worsen symptoms, so quitting is strongly advised. [65]

Fecal microbiota transplantation (FMT) involves transferring stool from a healthy donor to restore the patient’s gut microbiome. This approach shows promise with few side effects for Crohn’s and other IBDs. [69–70]

Functional medicine approach

As in other integrative approaches to autoimmune diseases, functional treatment for Crohn’s aims to uncover and address the root causes of inflammation.

An integrative physician may request food intolerance testing and stool analysis. Using these tools, they can collaborate with the patient to identify the underlying causes of inflammation. Potential triggers or aggravating factors may include certain foods, imbalances in the intestinal flora, bacteria, fungi, parasites, viruses, leaky gut syndrome, or a deficiency of beneficial intestinal bacteria. Based on personalized, patient-specific tests, integrative physicians can develop a tailored treatment plan that emphasizes nutrition, dietary supplements, exercise, and, in some cases, meditation. [71]

Recommended diets include: Specific Carbohydrate Diet (SCD), Elimination Diet. Both focus on removing symptom-triggering foods and emphasizing nutrient-dense options. [71]

Several dietary supplements may also be effective in treating Crohn’s disease. These primarily include anti-inflammatory agents such as omega-3 fatty acids and turmeric-based products. Zinc glycinate, N-acetylglucosamine, and vitamin D3 may assist in restoring the intestinal flora. [71]

Dr. Lum’s plan for Crohn’s & Ulcerative colitis

This is not a substitute for acute/emergency treatment but focuses on addressing the root causes and promoting healing [72]:

This approach focuses on addressing both genetic factors and treating underlying infections.

Step 1: Restoring digestion

Hydrochloric acid: It is important to restore the stomach’s natural ability to produce adequate amounts of hydrochloric acid to aid digestion. This involves supporting the healing and regeneration of the tissues and cells responsible for acid production.

Pancreatic enzymes: These digestive enzymes are essential for breaking down and absorbing food. Simply replacing the enzymes is not sufficient—the pancreas itself must also be treated and healed. The ultimate goal is to restore digestion so that it functions without the need for supplemental enzymes.

Bile: Inflammatory bowel diseases often disrupt bile production and flow. A common sign of this is experiencing digestive difficulties after consuming fatty foods. Proper bile function is crucial for fat breakdown and the absorption of fat-soluble vitamins (A, E, K, and vitamin D).

Bowel movements: Whether suffering from constipation or diarrhea, the goal of treatment is to restore balance to bowel movements, ensuring digestion is neither too slow nor too fast.

Step 2: Restoring the microbiome and treating infections

The microbiome directly influences the severity of inflammation, the health of the immune system, and overall digestion. Functional analysis of the gut microbiome plays a crucial role in recovery. Identifying and treating latent infections is essential for achieving long-term symptom relief.

Step 3: Identifying genetic predispositions

Genetic factors may worsen inflammation or impact neurotransmitter balance (serotonin, dopamine). Identifying these helps personalize recovery strategies.

Step 4: Assessing liver function

The majority of individuals with inflammatory bowel disease have underlying liver issues. However, conventional tests are often insufficient to fully exclude liver problems. A diseased liver can contribute to intestinal tract dysfunction. Supporting liver health and function may accelerate the healing of the intestinal tract.

In inflammatory bowel diseases, the body’s immune system attacks and attempts to eliminate harmful microbes, including viruses, bacteria, fungi, and parasites. This immune response leads to the chronic inflammation characteristic of these conditions.

When the microbiome is disrupted, the body’s defense system weakens, allowing infections to accumulate. The immune system then intensifies its efforts to combat these pathogens, triggering further inflammation.

This vicious cycle exacerbates the severity of Crohn’s disease symptoms. These symptoms tend to be cyclical, as various factors influence immune system health and inflammation severity.

Factors such as chronic sleep deprivation, food allergies, consumption of processed foods, and stress can worsen symptoms and weaken immune function. Therefore, treatment aims to strengthen the immune system by restoring gut microbiome balance and addressing underlying hidden infections.

The solution:

The goal is to balance the neurotransmitters serotonin and dopamine in both the brain and the gastrointestinal system. When these two neurotransmitters are balanced, excessive serotonin levels no longer trigger the inflammatory process, allowing the intestinal tissue to begin healing.

Treatment involves replacing serotonin and dopamine precursors (amino acid precursors) under medical supervision. Additionally, restoring the balance of the intestinal flora is crucial, which includes eliminating infectious pathogens, healing the intestinal wall, and strengthening the immune system.

Therefore, the integrative treatment of Crohn’s disease encompasses addressing identified nutritional deficiencies, optimizing the digestion and absorption of food and nutrients, achieving the appropriate quantity and ratio of intestinal bacteria, developing a personalized diet, and restoring a healthy intestinal flora. Treating genetic defects affecting neurotransmitters is one of the most important factors in achieving complete remission of inflammatory bowel diseases.

Another approach from functional medicine is Mullin’s DIGIN model [73]. This model assesses patient health across five fundamental areas: digestion and absorption, intestinal permeability, inflammation, the immune system, and the nervous system.

Other related conditions

Ulcerative colitis

The symptoms of Crohn’s disease are similar to those of ulcerative colitis, an inflammatory condition limited to the colon. Both are classified as inflammatory bowel diseases (IBDs) and often present with similar symptoms. However, it is essential to distinguish between the two, as their progression and treatment may differ. When the conditions cannot be clearly differentiated, the diagnosis is termed indeterminate colitis. [3], [8–9]

Crohn’s disease can affect any part of the gastrointestinal tract, while ulcerative colitis is generally confined to the colon [74]. In ulcerative colitis, inflammation is continuous throughout the affected area, whereas in Crohn’s disease, inflammation is segmental, appearing in multiple locations with healthy tissue between inflamed sections.

IBD

IBD stands for inflammatory bowel disease, a category that includes both Crohn’s disease and ulcerative colitis. According to a 2014 review, Crohn’s disease is typically more severe but less common than ulcerative colitis. [75]

IBS

Irritable bowel syndrome (IBS) is a common condition, affecting around 20% of the population. Like IBDs, including Crohn’s disease, IBS symptoms tend to be cyclical. Flare-ups may last for several days, and symptoms can worsen after eating. Women often experience increased symptoms during menstruation. [76]

IBS is usually associated with abrupt changes in bowel habits—diarrhea or constipation—and may present with symptoms such as [76]:

• diarrhea
• constipation
• abdominal pain
• cramps
• bloating and gas
• loud bowel sounds
• a feeling of incomplete evacuation
• mucus in the stool

Inflammatory bowel diseases (IBD), such as Crohn’s disease, and irritable bowel syndrome (IBS) share similarities in that both are incurable. They can cause similar symptoms, and diagnosing either condition is often a lengthy process. Another commonality is that both IBS and Crohn’s disease are chronic conditions, characterized by fluctuating symptoms that alternate between flare-ups and remission. Both can also manifest symptoms outside the digestive tract. [76]

The key difference is that IBD, including Crohn’s disease, is an autoimmune condition, whereas IBS is likely caused by digestive disturbances and an imbalance in the intestinal flora. Unlike ulcerative colitis and Crohn’s disease, IBS is not an inflammatory disorder. Medications can help reduce symptoms in people with IBD, while IBS treatment primarily focuses on lifestyle and dietary modifications. Furthermore, current knowledge indicates that, unlike Crohn’s disease, IBS does not increase the risk of developing intestinal cancer. [76]

References

[1] Mayo Clinic Staff, “Crohn’s disease – Symptoms and causes,” Mayo Clinic, 2020 https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304

[2] M. Pimentel et al., “Identification of a prodromal period in Crohn’s disease but not ulcerative colitis,” Am. J. Gastroenterol., vol. 95, no. 12, pp. 3458–3462, 0 2000, DOI: https://doi.org/10.1111/j.1572-0241.2000.03361.x

[3] D. C. Baumgart and W. J. Sandborn, “Crohn’s disease,” Lancet Lond. Engl., vol. 380, no. 9853, pp. 1590–1605, 0 2012, DOI: https://doi.org/10.1016/S0140-6736(12)60026-9

[4] N. R. C. (US) C. on D. and C. of J. Disease, Johne’s Disease and Crohn’s Disease. National Academies Press (US), 2003 https://www.ncbi.nlm.nih.gov/books/NBK207651/

[5] Z. Risoldi Cochrane and K. Holland, “Crohn’s Disease: Causes, Symptoms, Diagnosis, and More,” Healthline, Aug. 22, 2018 https://www.healthline.com/health/crohns-disease