The Gut Microbiome and the Immune System

The typical person has trillions of microbes in their body, collectively known as the microbiome. No two people have the same microbiome. The microbiome is dependent on both a person’s environment and their genes. Factors that affect the makeup of the microbiome include where a person lives, what they eat, how old they are, their physical activity level, and even how much stress they are under [1]. The first microorganisms are introduced into a baby’s gut in the mother’s womb, during birth, and through breastfeeding. As a child gets older, even more microbes are added from food, the environment, and other people.

There are two types of microbes in the body. Commensal microbes which include healthy “good” bacteria that keep the gut functioning and non-commensal microbes that include “bad” bacteria that make people sick. The immune system is the body’s defense force, which fends off these “bad” bacteria, but sometimes it can get confused [2]. When this confusion happens, the body start to fight against the “good” microbes, which results in inflammation of the intestine, eventually damaging the gut and causing the symptoms seen in Crohn’s disease. Crohn’s is most often diagnosed in 15–35 year old or 55–70 year old, and it affects many people: up to 1 in every 500 people in the world have Crohn’s [1].

Inflammation in Crohn’s Disease

Crohn’s disease was named after Dr. Burrill Crohn, who first described it in 1932 [2]. When the immune system gets confused in Crohn’s disease, it turns against the both the healthy and the bad bacteria in the gut setting off a cascade of damages. This causes inflammation, a natural reaction where the body sends immune cells to fight off what it thinks is harmful [3]. Normally, inflammation stops once the body heals, but in Crohn’s disease, the inflammatory process does not stop. Instead, it keeps going, causing pain, swelling, and eventually damaging the intestines (Figure 1). When good bacteria are seen as harmful, certain immune cells release chemical messages that cause more immune activity and inflammation which can result in long-term damage to the gut [3].

Some people are more at risk of getting Crohn’s disease because of their genes. Variations in immune system genes, which help regulate the immune system can make people more likely to have Crohn’s [3]. Scientists are not entirely sure why this happens and how to stop the immune system from turning against the gut by mistake.

What do People with Crohn’s Disease Experience?

Crohn’s disease is a chronic illness, which means that it affects a person for their whole life. People with Crohn’s have periods where they feel well and have no symptoms; this is called remission [4]. During other times, called flare-ups, they may experience symptoms of the disease. Crohn’s can affect any part of the gastrointestinal tract (Figure 2), from the mouth to the anus, but it most commonly affects the end of the small intestine and the beginning of the large intestine (also known as the colon).

People with Crohn’s often have chronic diarrhea, meaning they need to use the washroom more than three times daily. They may also feel pain on the right side of their abdomen, where the inflammation is often worse. Constant inflammation in the gut can make it harder for people to absorb important nutrients from food, leading to weight loss, tiredness, and lack of energy. People can also experience complications of the inflammation in the gut, like formation abscesses, a painful, swollen lump filled with pus due to infection and fistulas which are abnormal connection between body parts that should not be there. Most common fistula in Crohn’s disease is abnormal connection between the skin and the intestine.

Additionally, Crohn’s disease affects more than just the gut—it can also cause problems in other parts of the body, which are known as extra-intestinal symptoms. Some people experience joint pain and inflammation (which is called arthritis), inflammation in their eyes, or skin rashes.

How is Crohn’s Disease Treated?

While there is currently no cure for Crohn’s disease, there are ways to help manage the symptoms and improve the lives of individuals living with the disease. One of the first things doctors do to help manage Crohn’s is to help people eat smarter. This means teaching those diagnosed with Crohn’s disease to manage their diet in a way that does not trigger the symptoms of the disease. Foods can affect everyone differently, so it takes some trial and error to figure out which foods cause problems and which do not. Together with the doctor, Crohn’s patients try to:

• Identify trigger foods: common triggers include dairy, spicy foods, high-fiber grains, and fatty foods. A food diary can help people keep track of what they eat in a day, as well as whether they experience any discomfort that day or the next day, helping them track the cause of their symptoms [5].

• Focus on nutrition: because Crohn’s can interfere with how well the body absorbs nutrients, a balanced diet that is rich in proteins, easily digestible fiber, and essential vitamins and minerals can keep the disease in remission [5].

• Probiotics: “good” gut bacteria can help keep Crohn’s at bay and balance out the bad bacteria in the digestive system. Eating foods like yogurt or taking probiotic supplements might aid digestion and reduce symptoms, but this is a more debated topic of research and is not yet fully understood [6].

If diet changes do not work, some medications may help. One option is anti-inflammatory medication, which acts like a fire extinguisher for the digestive system, helping to calm down the excessive inflammation. Immune system modifiers are another option. These medicines act like peacekeepers, stopping the body’s immune system from overreacting and causing the inflammation in the first place by dampening the immune system response. Finally, more recently, special medications called biologics have been developed. These target specific parts of the immune system like immune receptors that activate the immune response in Crohn’s disease specifically to prevent them from causing inflammation [3]. Biologics are more specific and tailor-made to prevent the development of Crohn’s disease whereas immune system modifiers are general immune system suppressants.

Working with a doctor, dietitian, and other healthcare workers to understand what to eat and what to avoid can significantly improve the quality of life for those with Crohn’s.

What Have we Learned?

Living with Crohn’s disease is a lifelong challenge. While scientists do not yet know the exact cause of the disease, they know it involves a mix of genes, the immune system, the gut microbiome and the environment. The constant and excessive inflammation caused by Crohn’s can make it hard for the body to absorb the essential nutrients needed to remain healthy and strong. That is why people with Crohn’s often need to follow special diets, avoid certain trigger foods, and take medications to manage their symptoms. As of right now, no cure exists; however, researchers and doctors are making great progress in understanding the disease and its causes and developing better treatments that help reduce inflammation while preventing complications and permanent damage. With continued research, there is hope for a future where a cure for Crohn’s disease is discovered.

Glossary

Microbiome: ↑ Group of living organisms, made up mostly of bacteria that live in the body (especially the gut) that help with digestion, immune regulation, metabolism and protection from external pathogens.

Immune System: ↑ The body’s built-in defense system from external and internal forces, like bacteria, infections and even the body’s own cells.

Inflammation: ↑ Result of an immune system cascade as a response to injury or infection leading to swelling, redness, heat and/or pain.

Chronic: ↑ A condition or disease that lasts for a long-time or reoccurs.

Remission: ↑ Period of time where symptoms of a disease are under control and the disease is controlled.

Flare-ups: ↑ Periods where symptoms of a disease either worsen or come back after disease was previously under control.

Probiotics: ↑ Good bacteria that can help strengthened the gut, found in tablets and certain foods.

Biologics: ↑ Specialized medication that resemble the body’s own cells made from living cells to help control inflammation and curb immune system overactivation.

Conflict of Interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

AI Tool Statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

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