Introduction

One type of cancer that starts in the lymphatic system is lymphoma. Lymphoma is a cancer where abnormal white blood cells grow uncontrollably. The lymphatic system is made up of many vessels, organs, and tissues that move a clear fluid called lymph throughout the body. 

This fluid leaks out of our blood and carries away debris like old or abnormal cells and pathogens (organisms that enter our body and cause disease). Some other functions include absorbing fat and fat soluble vitamins to keep the levels of our body fluids normal. 

One of the major immune tissues involved in the lymphatic system is MALT (Mucosa-Associated Lymphoid Tissue). But what exactly MALT is, how it get affected by bacteria like Campylobacter Jejuni? Read on to find out!

What is MALT?

MALT stands for Mucosa-Associated Lymphoid Tissue. It’s found in areas exposed to the external environment and makes mucus. It is a part of the immune system found in the lining (mucosa) of various organs such as the gut, nose, airways, eyes, and others.

MALT is split into different categories based on its location in the body. Some examples are GALT (Gut-associated lymphoid tissue), NALT (Nasopharynx-associated lymphoid tissue that is located in the back of the nose and throat) and CALT (Conjunctiva-associated lymphoid tissue. Conjunctiva is the thin membrane that covers the white of our eyes).

MALT and the other sites make up the common mucosal immune system. This is a specialised branch of our body's general immune system. An interesting aspect of the mucosal immune system is that activation in one site can trigger the immune response at another, like activation in the nose can result in immune responses in the gut. This means that if a pathogen is detected in the nose, antibodies can be made in different sites to protect us.

Much like a factory, MALT can be split into 2 main sites. The ‘inductive sites’ wherein immune cells are switched on to produce antibodies, and ‘effector sites’ where these antibodies are released to protect the surface of the mucosal tissues. This is important because mucosal surfaces, such as in the gut, lungs, and nose, are constantly exposed to the environment. As a result, they can be accessed by both harmless and harmful microorganisms and bacteria. The mucosal immune system stops harmful invaders, like pathogens, from entering the body.

Campylobacter jejuni and MALT

Well, Campylobacter jejuni is a type of bacterium that causes food poisoning. In rare cases, long term infection with this bacterium can lead to a cancer called MALT lymphoma, particularly in the small intestine. MALT lymphoma is a slow-growing cancer that starts in the MALT. When it occurs in the small intestine, it is sometimes associated with chronic bacterial infections, such as Campylobacter jejuni. The reason behind this is that our immune system is active for a long time, trying to fight off this bacterium; therefore, abnormal cells may slip undetected and grow into tumours.

What is Campylobacter jejuni?

Let’s dive deeper into Campylobacter jejuni. C. jejuni (pronounced kam-py-lo-bak-ter je-joo-nee) is one of the most common bacteria that cause food related illness. It typically leads to a condition called bacterial gastroenteritis, with symptoms like diarrhoea, fever, nausea, and abdominal cramps. Most people infected with C. jejuni experience symptoms within 2–5 days. The illness is usually mild to moderate and goes away on its own within about a week. 

The name Campylobacter comes from the Greek kampylos (curved) and baktron (rod), and translates to “curved rod”. C.jejuni is a pathogenic species of bacteria that is heavily monitored globally through surveillance programmes. These include whole genome sequencing (WGS) analysis of Campylobacter isolates. In the UK alone, the number of reported Campylobacter cases in England rose from 60,055 in 2023 to 70,352 cases in 2024, an increase of 10,297 cases (17.1%) with a resulting rate rise from 104.1 to 121.9 reports per 100,000 population.

In addition, report increases were seen across all age groups, but the highest number of laboratory reports remained in the cases aged 50 to 79 years, accounting for 44.0% of the total number of reports. Finally, the month with the most reported cases of Campylobacter in 2024 was June, consistent with the previous 5-year median; however, high levels of reporting extended to October. Overall, of the 9 foodborne outbreaks reported to national surveillance, 5 were likely associated with consumption of liver or products containing poultry liver, such as pâté or parfait.

So how do people get infected with C. jejuni? 

Campylobacter is a zoonotic bacterium, meaning it can be transmitted from animals to humans. The main sources of infection are undercooked poultry (especially chicken), raw milk, or contaminated water.

Sometimes contact with infected animals, most commonly chickens, pigs, and cattle, can lead to disease, but there have been instances of the disease being spread even from domestic cats and dogs. Poor food handling, improper cooking, and contaminated drinking water are the most common ways people come into contact with the bacteria.

While most infections are mild, some people can develop severe complications such as bloodstream infections, reactive arthritis and Guillain-Barré syndrome (a rare condition where the immune system attacks the nerves). C. jejuni is especially skilled at moving through the body’s protective mucus lining in the gut. 

Mechanism of action

Let’s explore how this works. The bacterium has a spiral-shaped body that resembles a spring and a flagellum, which is a tail-like whip at both ends. It moves in a corkscrew motion and can drill through the thick mucus layer of the intestines. This is different from many bacteria, which can’t swim through mucus as effectively.

C. jejuni also uses chemoreceptors -special proteins called Tlp proteins -to sense its environment. These receptors detect chemicals outside the bacteria and help them move toward favourable conditions (like nutrients) or away from harmful ones. This helps the bacteria locate the best places in the gut to settle and multiply, known as colonisation niches.

The bacteria specifically target intestinal crypts, which are tiny pockets in the lining of the intestine. These areas are rich in nutrients, slightly shielded from the immune system and offer the best conditions for the bacteria to live and grow. Campylobacter jejuni primarily affects the small intestine, where it upsets the normal balance of bacteria, causes inflammation, and triggers diarrhoea.

What is IPSID?

Immunoproliferative Small Intestinal Disease (IPSID) is a rare subtype of MALT lymphoma that mostly affects the upper small intestine. IPSID typically affects young adults and is most commonly found in the Middle East. Patients usually present with symptoms of malabsorption, like chronic diarrhoea, weight loss, and nutrient deficiencies. Interestingly, IPSID has been linked to C. jejuni infections in a few studies.

Scientists are still investigating the exact cause of IPSID. A recent study by Lysa A. Baginsky et al suggests that there is a possible link between IPSID and chronic infection with C.jejuni. They found that C. jejuni was present in 47% of IPSID cases (12 out of 27 patients), 16% of other intestinal lymphomas (14 out of 87 cases), and 0% in non-intestinal lymphomas and normal/reactive intestinal biopsies.

In addition, when treated with antibiotics for C. jejuni patients with IPSID improved, meaning that there was a link between C.jejuni and IPSID. All these findings show that there may be a potential association between C. jejuni and IPSID; however, more research is needed to establish this as fact.

Overall, while more research is needed to fully understand the role of C. jejuni in the development of MALT lymphomas such as IPSID, there is some evidence supporting a strong association. More studies into the exact mechanism of how C.jejuni causes IPSID can help clarify C. jejuni's role in small intestinal MALT lymphomas. In the future, this can open exciting new avenues for early diagnosis of small intestinal MALT lymphomas and targeted treatment.

Summary

• Small intestinal MALT lymphomas are a type of cancer that affects the lymphatic system, leading to abnormal growth of white blood cells in the intestinal lining
• Campylobacter jejuni is a bacterium that can cause bacterial gastroenteritis, with symptoms like nausea, stomach ache and diarrhoea. It is usually transmitted from animals such as chickens to humans. The main routes of infection involve undercooked poultry, contact with contaminated water and raw milk
• IPSID is a rare subtype of small intestinal MALT lymphoma, usually present in adolescents in the Middle East. Some studies have shown a possible link between chronic C. jejuni infection and the development or progression of IPSID. This suggests that colonisation of the gut by C. jejuni may contribute to the development of small intestinal MALT lymphomas
• More research is needed to establish a definitive link between the two and find the precise mechanism involved. In the future, this can lead to advancements in the diagnosis and treatment of small intestinal MALT lymphoma