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• In inflammatory bowel disease (IBD), the immune system attacks the cells that form the lining of the gut. This causes pain and discomfort.
• In a new study, scientists have identified a type of immune cell that can initiate repair of the gut lining following inflammation.
• Importantly, they have discovered a way to switch the cells from promoting inflammation to promoting repair.

The Centers for Disease Control and Prevention (CDC) estimate that in 2015, 3.1 million people in the United States had IBD.

IBD is an umbrella term for a number of conditions, including ulcerative colitis and Crohn’s disease. It is not the same as irritable bowel syndrome, which does not cause inflammation.

Some common symptoms of IBD include:

• abdominal pain
• persistent diarrhea
• rectal bleeding or bloody stools
• weight loss
• fatigue

Experts are still not sure what causes IBD, but they know the condition involves the immune system attacking tissues that line the gut, even though there is no infection. This autoimmune response causes inflammation and ulceration of the gut lining.

Treatments such as corticosteroids can reduce this inflammatory response. However, in the process, they can also inhibit other parts of the immune system involved in repairing damaged tissue.

In particular, immune cells called macrophages play a role in both inflammation and healing of the intestinal lining. Macrophages can ingest cellular debris and microorganisms, but they also release signaling molecules that initiate inflammatory or repair processes.

The molecular mechanism that flips them from inflammatory mode to repair mode has been a mystery, however.

Molecular master switch

Researchers at KU Leuven in Belgium and Seoul National University in the Republic of Korea set out to discover this molecular “master switch.” They started by investigating macrophages in the intestines of people with IBD.

When the participants were experiencing a flare-up of their condition, the scientists found that they had low numbers of a particular type of macrophage in their gut, compared with individuals who do not have IBD.

When their condition went into remission, however, these macrophages increased in number.

The cells in question had receptors in their membrane for a hormone-like signaling molecule called prostaglandin E2 (PGE2), which is associated with tissue regeneration.

“If the [participants] had acute disease, they had a lower amount of these beneficial cells, and if they went into remission, then amounts of macrophages went up,” says lead study author Prof. Gianluca Matteoli, an immunologist at the Translational Research Center for Gastrointestinal Disorders at KU Leuven.

“This suggests that they are part of the reparative process,” he adds.

The scientists report their findings in the journal Gut.

Animal model

Next, the researchers investigated the equivalent type of macrophage in a mouse model of ulcerative colitis, which is one form of IBD.

They discovered that cells with receptors for PGE2 were few and far between in animals with the condition. However, when the scientists increased levels of PGE2 in the animals’ guts, these cells responded by releasing a substance called CXCL1, which promotes tissue regeneration.

To confirm that PGE2 receptors are responsible for switching macrophages from inflammatory mode to healing mode, the researchers created mice whose bodies were unable to make the receptor.

As the scientists predicted, these mice struggled to repair the cells lining their gut.

In a final experiment, the researchers restored the macrophages’ powers of healing by providing a drug that stimulated the cells to make CXCL1.

They delivered this drug inside artificial spherical vesicles called liposomes, which the macrophages ingested.

“We already knew that prostaglandins were important for inducing proliferation of tissue cells, but this study shows that they are also important for controlling the inflammatory effect, so moving the body from the acute stage where inflammation dominates to the reparative stage.”

– Prof. Gianluca Matteoli

Drug delivery system

Study co-author Prof. Seung Hyeok Seok led a team at Seoul National University that created the drug delivery system.

The researchers are planning more detailed investigations into the types of human macrophage involved at different stages of IBD. Their long-term goal is to design drugs that will turn off inflammation and promote tissue repair.

“We want to identify other factors that trip the switch that turns macrophages from inflammatory cells to non-inflammatory cells,” says Prof. Matteoli. “Then, using the liposome technology that Prof. Seok has developed, these could be used to target the macrophages and so produce very precise drugs.”

In their paper, the researchers conclude:

“Our results pave the way for the development of a new class of therapeutic targets to promote macrophage healing functions and favor remission in [people] with IBD.”

What to know about inflammatory bowel disease

Inflammatory bowel disease (IBD) refers to several long-term conditions that involve inflammation of the digestive tract, or gut.

According to the Centers for Disease Control and Prevention (CDC), up to 3 million people in the United States now have IBD. The majority of people with IBD receive their diagnosis before they reach 30 years of age.

This article explores the different types of IBD and how the condition compares with irritable bowel syndrome (IBS). It also covers IBD’s symptoms, causes, and treatment options.

Types of IBD

Share on Pinterest A person with IBD may experience blood in the stool, fatigue, and weight loss.

The two main types of IBD are ulcerative colitis and Crohn’s disease. The sections below will discuss these in more detail.

Ulcerative colitis

This condition causes inflammation in the large intestine, or colon. There are several different classes of ulcerative colitis, depending on location and severity. These are:

• Ulcerative proctitis: This type occurs when inflammation stays within the rectum. It tends to be the mildest form of ulcerative colitis.
• Universal colitis, or pancolitis: This type occurs when inflammation spreads across the entire colon.
• Proctosigmoiditis: The type occurs when the rectum and lower end of the colon experience inflammation.
• Distal colitis: This type occurs when inflammation extends from the rectum and up the left colon.
• Acute severe ulcerative colitis: This is a rare type that causes inflammation across the entire colon, leading to severe symptoms and pain.

Crohn’s disease

Crohn’s disease can affect any part of the digestive tract between the mouth and the anus. However, it most commonly develops in the final section of the small intestine and colon.

This type of IBD has become more common over time. In fact, around 500,000 people in United States now have it, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

They also suggest that Crohn’s disease is most likely to develop when a person is aged 20–29.

Other

If a doctor is unable to distinguish between the two main types of IBD, they will class a person’s condition as “indeterminate colitis.”

Some other types of IBD include lymphocytic colitis and collagenous colitis.

Comparing IBD and IBS

There are some similarities between IBS and IBD. For example, they can both lead to changing bowel habits and pain in the abdomen. The symptoms of both also tend to flare-up for short periods, then go into remission.

Neither has a cure that can completely resolve the condition.

For these reasons, people often confuse IBD with IBS. However, the two conditions are different in the following ways:

• IBD is a more severe condition that may lead to a number of complications, including malnutrition and damage to the bowel.
• IBD occurs due to an overactive immune system, which leads to inflammation throughout the gut and gastrointestinal tract. IBS usually develops due to digestive problems or an oversensitive gut.
• Treating IBD involves medications that reduce inflammation. People with IBS can reduce their symptoms by making changes to their diet or lifestyle.

Causes and risk factors

Several factors can contribute to the development of IBD. For example, it may occur because the immune system has an irregular response to bacteria, viruses, or food particles. This can trigger an inflammatory reaction in the gut.

Research has also linked Escherichia coli to Crohn’s disease.

Although there is currently no single confirmed cause of IBD, there are several potential factors that can increase a person’s risk of developing each of the conditions within IBD.

The sections below will discuss these in more detail.

Risk factors for ulcerative colitis

• Age: Most people receive a diagnosis at around 15–30 years of age or after 60 years of age.
• Ethnicity: People of Jewish descent seem to have a high risk of ulcerative colitis than other ethnic groups.
• Genetics: People with a close relative who has ulcerative colitis have a higher risk of developing it themselves.

Risk factors for Crohn’s disease

Health professionals do not fully understand what causes Crohn’s disease. However, they have identified several factors that may increase a person’s risk of developing it, including:

• Genetics: People who have a parent or sibling with Crohn’s disease are more likely to develop it themselves.
• Medications: The use of certain medications — including nonsteroidal anti-inflammatory medications (NSAIDs), birth control, and antibiotics — may increase the risk of Crohn’s disease.
• Smoking: This habit can increase the risk of Crohn’s by double.
• Diet: A diet that contains high levels of fat can also increase the risk of Crohn’s disease.

Symptoms

The symptoms of IBD may vary according to the type, location, severity.

People might experience periods when symptoms worsen (flares) and periods with few or no symptoms (remission). Flares may vary in amount, intensity, and duration.

According to the CDC, the following symptoms are common to both the main types of IBD:

• blood in the stool
• persistent diarrhea
• fatigue
• weight loss

The Office on Women’s Health (OWH) suggest that IBD may also lead to symptoms outside the digestive system, including:

• fever
• joint pain
• skin conditions

The OWH also suggest that IBD can make the effects of menstruation more severe, and that IBD symptoms may also get worse during menstruation. IBD also increases a woman’s risk of iron deficiency anemia.

Complications

Health professionals have linked a number of complications to IBD. Some of them could be life threatening.

According to the NIDDK, some possible complications of Crohn’s disease include:

• bowel obstruction
• colon cancer
• fistulas, which are abnormal tunnels in the gut
• small tears in the anus, or anal fissures
• ulcers in the mouth, intestines, anus, or perineum, which is the area between the genitals and anus
• malnutrition

They also suggest that ulcerative colitis can cause the following complications:

• rectal bleeding, which may lead to iron deficiency anemia
• dehydration
• poor absorption of nutrients
• reduced bone density, possibly leading to osteopenia or osteoporosis

A 2018 review also linked IBD to the development of kidney stones.

Diagnosis

To diagnose IBD, a health professional will take a full medical history, before requesting one or more diagnostic tests. Some tests they may use include:

• stool samples
• blood tests, to check for anemia or infection
• X-rays, if they suspect a serious complication
• CT or MRI scans, to detect fistulas in the small intestine or anal region

A health professional may also request endoscopic procedures. During these, they will insert a flexible probe with a camera attached through the anus.

These procedures help reveal any intestinal damage and allow the health professional to take a small sample of tissue for examination.

Some types of endoscopic procedure a health professional may use to diagnose IBD include:

• Colonoscopy: They use this to examine the entire colon.
• Flexible sigmoidoscopy: This examination helps them check the final section of the colon.
• Upper endoscopy: This procedure allows them to examine the esophagus, the stomach, and the first part of the small intestine.

A capsule endoscopy is another option. This procedure requires a person to swallow a capsule that contains a camera, thereby allowing a health professional to examine the small intestine.

Treatment

There is currently no cure for IBD. The goal of treatment will be to reduce the symptoms, achieve and maintain remission, and prevent complications.

The most common treatments for IBD are medications and surgery, which the sections below will discuss in more detail.

Medication

Doctors may prescribe certain drugs to treat IBD, beginning with milder ones and working up to more aggressive treatments later. These medications may include:

• Anti-inflammatory drugs: 5-ASA medications are typically the first line of defense against IBD symptoms. They reduce inflammation in the gut and may help a person achieve and maintain remission.
• Corticosteroids: A doctor may prescribe fast-acting anti-inflammatory steroids if a milder class of anti-inflammatories is not effective. People should only use these drugs short-term to treat flares. Long-term use of NSAIDs may make IBD symptoms worse.
• Immune suppressors: These work by preventing the immune system from attacking the bowel cells, leading to reduced inflammation. However, they can take around 3 months to take effect, and they may cause a number of side effects, such as an increased risk of infection.
• Biologic therapies: These are antibodies that target certain substances that cause inflammation in the body.

Some other medications that can reduce IBD symptoms include:

• antibiotics
• antidiarrheal drugs
• laxatives
• vitamin and mineral supplements, for cases of nutritional deficiency due to IBD

Surgery

In some cases, surgery may be necessary to treat IBD or its complications. For example, a doctor may recommend surgery to widen a narrow bowel or remove any fistulas.

People with ulcerative colitis may need to undergo surgery to remove the colon and rectum. Those with Crohn’s disease may need a procedure to remove certain portions of the intestines.

Lifestyle changes

Certain dietary and lifestyle factors can make IBD symptoms worse. However, making positive changes to these habits can help a person manage their symptoms, reduce flares, and even maintain remission.

Diet

Some dietary measures that may benefit people with IBD include:

• keeping a food diary to track whether or not certain symptoms occur after eating certain foods
• limiting the intake of dairy products
• restricting the intake of high fat foods
• avoiding or limiting the intake of spicy foods, caffeine, and alcohol
• limiting the intake of high fiber foods, particularly if the bowel has narrowed
• eating frequent small meals, rather than several large ones
• drinking plenty of water
• taking vitamin and mineral supplements, to prevent deficiencies

Stress

Many people with IBD say that they experience more severe symptoms during stressful periods. Therefore, learning to manage stress may help reduce the frequency and severity of these types of flares.

Some stress management techniques include:

• exercise
• meditation
• breathing exercises
• progressive muscle relaxation
• engaging in hobbies and other enjoyable activities

Smoking

Recent research has shown links between smoking and Crohn’s disease. Smoking is a risk factor for developing the condition and can make the symptoms worse.

Other research has suggested that smoking may actually benefit those with ulcerative colitis. However, the same researchers also found that the health risks associated with smoking far outweigh any benefits.

Emotional support

IBD can have a significant emotional impact, especially on those with severe symptoms. For this reason, it is important to have a strong support network among family and friends.

People with IBD might also consider joining a support group or attending counseling sessions, which they may find beneficial.

Healthline provide an app that connects people with IBD and helps them get support when they need it.

Prevention

The exact cause of IBD is not yet clear. For this reason, it is difficult to know how best to prevent it.

Genetic factors associated with IBD are beyond a person’s control. However, a person can reduce their risk by eating a healthful diet, quitting smoking, and exercising regularly.

Outlook

Although there is currently no cure for IBD, it may be possible to manage the condition with medical interventions and lifestyle changes.

According to the Crohn’s & Colitis Foundation, with effective treatment, around 50% of people with Crohn’s disease will be in remission or have only mild symptoms within the next 5 years.

Also, around 45% of those in remission will not experience a relapse in the next year.

In any given year, 48% of people with ulcerative colitis are in remission and 30% have mild symptoms. The longer someone remains in remission, the less likely they are to experience a flare during the following year.

Death due to IBD or its complications is rare. People with Crohn’s disease have only a slightly higher overall mortality rate than those without it. Those with mild-to-moderate ulcerative colitis do not have a higher mortality rate than those without IBD.

If a person experiences any persistent bowel habit changes or has any other symptoms of IBD, they should seek consultation with their doctor.