Big-picture thinking needed for inflammatory diseases

When it works well, our immune system keeps us alive and healthy. We need that complex system of cells and molecules to prevent life-threatening infections and to heal injuries.

But the immune system isn’t always seen as the good guy: research shows it is often perturbed in many chronic conditions including asthma, rheumatoid arthritis and inflammatory bowel disease.

To tackle these complex conditions more effectively, Prof Fergus Shanahan believes we need to look beyond the immune system. In a public lecture tomorrow he will look at the bigger picture of the immune response, and particularly how the trillions of microbes that live comfortably in our bodies can “educate” that response early in life.

Immune response

Shanahan, a consultant gastroenterologist and professor of medicine at University College Cork, has an issue with the label "auto-immune" disease being applied to conditions such as rheumatoid arthritis, lupus, multiple sclerosis, Crohn's disease, asthma and type 1 diabetes.

“If you call it auto-immune, then you imply that the fault lies within the immune system, but this is loose terminology,” he says. “The immune system is involved, but it is not the only factor, and if you keep using terminology such as auto-immune, you run the risk of focusing only on the immune system and not looking elsewhere.”

And there are plenty of other places to look, he argues, including the interplay between the immune system and other complex biological control networks in the body.

For that reason, he prefers to think about the immune response rather than the immune system. “If you are challenged by an infection or some danger, the immune response is really a network of nerve, hormone, metabolic and immune systems,” he explains. “And that whole network of responses has an influence on your health and how your body reacts.”

That broader network being disrupted in illness may help to explain why chronic diseases can often occur together in the same patient, and how chronic inflammation and obesity can go hand in hand, Shanahan notes.

“A lot of patients with chronic inflammatory disorders are at increased risk of obesity and other metabolic conditions such as diabetes and high blood pressure, but if the overall immune response is a network of all those systems, then that shouldn’t be a huge surprise.”

Broader perspective

Immunologist Prof Luke O’Neill agrees it’s wise to take the broader perspective for chronic inflammatory diseases. “The big picture for many chronic diseases will most likely involve our immune system interacting with other systems in our bodies, and that presents great potential for new therapies,” says O’Neill, who is professor of biochemistry at Trinity College Dublin.

Earlier this month, O’Neill hosted a conference in Germany about links between cancer and the immune system, and he welcomes these new perspectives.

“Even cancer and inflammation are now thought to be interrelated, and if we can understand the mechanics of these relationships, we can hopefully identify new targets to tackle them.”

Early education

Shanahan’s particular area of expertise is the “gut microbiota” or the collection of microbes that live in our intestines. He believes the bacteria that make our bodies their home early in our lives have an important role to play in educating our immune response.

“The trillions of bugs that colonise our skin, our bowel and our lungs give us our immune education,” he says.

If those early bacteria get disturbed by antibiotics, there could be long-term consequences, notes Shanahan, who directs the Alimentary Pharmabiotic Centre (APC) in Cork. “There’s good, convincing data that [taking] courses of antibiotics early in the first year of life is a risk factor for developing inflammatory bowel disease and asthma,” he states.

“It’s not a guarantee that if you get a course of antibiotics you are going to develop these diseases: it is a statistical observation, and you probably also need the genetic susceptibility too, but the genes that make you susceptible are quite common.”

He also cites “less compelling” evidence of a link between early antibiotic exposure and a risk in later life of obesity and diabetes, and describes how animal studies indicate that if the microbes are perturbed or absent early in life, they can develop a bowel sensitivity “similar to irritable bowel syndrome” as adults.

Protective measures

To help protect the overall immune response from youth to old age, Shanahan offers some advice: exercise, don’t smoke, avoid antibiotics unless absolutely essential, and eat a varied diet.

“It is common sense,” he says. “But common sense is not much use to us unless we believe it, and sometimes we need to see mechanisms to believe it.”

The nutritional advice particularly stood out to Shanahan when the APC analysed the diets and gut microbes of older people and found that more varied diets were linked with a greater diversity of bacteria in the gut and better overall health.

While the study was on older people, Shanahan believes we should all take heed of its findings.

“Diversify your diet,” he says. “We are feeding our microbes as well as feeding ourselves.”

Prof Fergus Shanahan will receive the 2015 Irish Society for Immunology Public Lecture Award tomorrow, April 29th, at 7pm in the Trinity Biomedical Sciences Institute, Pearse Street, Dublin 2. The talk is free, open to the public and booking is not required. For more information, email irishimmunology@gmail.com