Genetics alone cannot explain who develops IBD. It's time to look at our environment and lifestyle, researchers say.
Inflammatory bowel disease (IBD) is an umbrella term for the myriad of conditions that affect the gastrointestinal tract.
Researchers aren't exactly sure why or how IBD develops, but a dysfunctional immune system that attacks the body's own tissues is a classic sign of the condition.
Chronic inflammation causes the formation of ulcers and serious tissue damage, causing the symptoms that people affected by IBD experience. These include abdominal pain, diarrhea, weight loss, fatigue, and anemia. There is currently no cure for IBD.
According to the Centers for Disease Control and Prevention (CDC), an estimated 1–1.3 million people in the United States have some form of IBD, and the number is steadily rising.
While research is continuing to find genes linked to IBD risk, the focus has increasingly shifted to environmental and lifestyle factors.
Here, we look at research that has been published this year and shine the spotlight on the roles that industrialization, urban environments, and our inherited gut microbiomes play in IBD.
More than 200 genes identified
While no single underlying cause for IBD has been identified, genetics certainly play a role.
Jeffrey C. Barrett, Ph.D. — who is a senior group leader from the Wellcome Trust Sanger Institute in Cambridge in the United Kingdom — explains in an article published in the Journal of Autoimmunity that identical twins had nearly 10 times the rate of Crohn's disease and nearly four times the rate of ulcerative colitis as non-identical twins.
This "[...] support[s] the importance of genetics in IBD risk," he says. But it is not straightforward.
What are all these genetic data telling us about IBD?
Certain biological processes or pathways keep on cropping up. These include genes involved in the innate immune response — including some genes responsible for keeping the lining of our gut intact — as well as those involved in the activation and regulation of the adaptive immune response.
Perhaps these findings come as no surprise; the classic hallmark of IBD is a dysregulated immune response. However, without detailed knowledge of how these pathways are disrupted, treatments will mostly focus on symptoms, rather than the underlying causes of the condition.
Yet genetics can only explain a proportion of the risk associated with developing IBD.
IBD arises 'in newly industrialized countries'
Prof. Gilaad G. Kaplan — who is a gastroenterologist and epidemiologist at the University of Calgary in Canada — and colleagues recently published an article in The Lancet that highlights how IBD rates have evolved across the globe.
In North America, Australia, and most countries in Europe, IBD rates are estimated to have passed the 0.3 percent mark, but the number of new cases diagnosed each year has reached a plateau.
"More striking," explains Prof. Kaplan, "is the observation that as newly industrialized countries have transitioned towards a westernized society, inflammatory bowel disease emerges and its incidence rises rapidly."
Industrialization and a Western lifestyle are now clearly in the mix of culprits to blame for rising IBD rates.
"During the past 100 years, the incidence of inflammatory bowel disease has risen, then plateaued in the western world, whereas countries outside the western world seem to be in the first stage of this sequence."
Prof. Gilaad G. Kaplan
This puts IBD squarely into the category of being a global burden, posing significant challenges for doctors and health policy makers.
"Consequently," Prof. Kaplan adds, "these countries will need to prepare their clinical infrastructure and personnel to manage this complex and costly disease."
But healthcare expenditure for IBD is very high: the cost of treating the condition in the U.S. has been estimated to be in the region of between $14.6 and $31.6 billion each year.
Our living spaces influence IBD risk
Back in July, we reported on a population study that looked at the influence of rural and urban environments on IBD.
While there was already evidence from several individual studies and a systematic review, pointing at the role of our living spaces on the chances of developing IBD, there were inconsistencies between the different study designs.
The research — which was led by Dr. Eric I. Benchimol, an associate professor at the University of Ottawa in Canada — identified that living in a rural environment offered significant protection against IBD, particularly in those below the age of 18.
The study involved more than 45,000 people, of which 14.6 percent lived in a rural postcode, and more people were city dwellers at the time that they received their IBD diagnosis.
In order to study the effect of early life exposure on subsequent IBD risk, Prof. Benchimol and his colleagues also assessed 331 rural IBD patients and compared them with 2,302 urban patients.
"Exposure to the rural environment from birth was consistently associated with a strong protective association with the development of IBD later in life, whether children were exposed continuously for 1 to 5 years from birth."
Prof. Eric I. Benchimol
He adds that "the mechanism by which rurality protects against IBD is uncertain, and may include dietary and lifestyle factors, environmental exposures, or segregation of individuals with different genetic risk profiles."
Inheritance, but not as we know it
Dr. Martin Blaser — a professor of medicine at the New York University School of Medicine in New York City — and team study the human microbiome. Previous work by Prof. Blaser and other groups indicates that antibiotics have a long-lasting effect and increase the level of risk of developing IBD that we inherit from our mothers.
The initial boost of microbes that we are exposed to at birth is crucial in getting our immune system off to a good start.
In a new study in Nature Microbiology, Prof. Blaser and colleagues found that it is not the antibiotics per se that cause an increase in IBD risk. Rather, antibiotic use changes the mother's microbiome, which is then passed to the baby at birth.
"Our results provide strong evidence that antibiotics change the baby's inherited microbial communities with long-term disease consequences, which is especially important given the widespread use of antibiotics in young women before and during pregnancy."
Prof. Martin Blaser
Mice that were genetically engineered to carry increased susceptibility to ulcerative colitis showed a 55-fold increase in bowel inflammation when they inherited their mother's antibiotic-treated gut bacteria.
This means that mothers can pass on an increased risk of developing IBD to their children not via their genes, but via their own microbiome.
"The basis for inheritance of IBD might possibly be quite different from what we had been thinking for many years," explains Prof. Blaser.
What does the future hold?
Prof. Kaplan concludes his article by saying, "[T]he changing global burden of inflammatory bowel disease during the next decade will require a two-pronged solution that involves research into interventions to prevent inflammatory bowel disease and innovations in the delivery of care to patients with inflammatory bowel disease."
By combining the research efforts of geneticists, epidemiologist, microbiologists, physicians, and pharmaceutical scientists, we will hopefully get to the bottom of the many factors that influence whether a person develops IBD.
Armed with this knowledge, we can look to new treatments and technologies that aim to address the underlying disease pathways, and — crucially — the environmental and lifestyle factors that clearly contribute to inflammatory bowel diseases.