Inflammatory bowel disease is on the rise, especially in countries that adopt a Western lifestyle. Find out what the research reveals about how modern lifestyle affects our chances of developing inflammatory bowel disease.

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Genetics alone cannot explain who develops IBD. It is 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.

Crohn’s disease and ulcerative colitis are the most common forms of IBD.

Researchers are not 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, resulting in the symptoms that people with IBD most commonly 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 3.1 million people in the United States have some form of IBD, and the number is steadily rising.

While research continues to find genes linked to IBD risk, the focus has increasingly shifted to environmental and lifestyle factors.

Here, we look at the research and shine the spotlight on the roles that industrialization, urban environments, and our inherited gut microbiomes play in IBD.

While there is no identifiable single underlying cause for IBD, genetics certainly play a role.

Jeffrey C. Barrett, PhD — a senior group leader from the Wellcome Trust Sanger Institute in Cambridge in the United Kingdom — explains that identical twins had nearly 10 times the rate of Crohn’s disease and nearly four times the rate of ulcerative colitis as nonidentical twins.

This “[…] support[s] the importance of genetics in IBD risk,” he says. But it is not straightforward.

A 2023 mini-review notes that in a study on 91 twin pairs, where at least one twin had IBD, out of 42 pairs, one or both had Crohn’s disease and out of 41 pairs, one or both had ulcerative colitis. Other studies have shown that identical twins have a rate of 20–60% of Crohn’s disease and 3–5% in nonidentical twins.

Experts have now linked more than 200 genetic variations in the DNA code, and this number continues to rise as molecular biology technology becomes ever more sophisticated.

What are all these genetic data telling us about IBD?

Certain biological processes or pathways keep 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.

However, genetics can only explain a proportion of the risk associated with developing IBD.

Professor Gilaad G. Kaplan — a gastroenterologist and epidemiologist at the University of Calgary in Canada — and colleagues highlighted how IBD rates have evolved across the globe.

In North America and Europe, experts estimate that over 3 million people have IBD. Rates are estimated to have passed the 0.3 percent mark in North America, Oceania, and many European countries.

“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 factors 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 policymakers.

“Consequently,” Prof. Kaplan adds, “these countries will need to prepare their clinical infrastructure and personnel to manage this complex and costly disease.”

However, healthcare expenditure for IBD is very high: A 2023 study found that the estimated annual cost of treating ulcerative colitis in the United States was $22,331,079, and $15,183,678 for Crohn’s disease.

In 2017, MNT 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 — 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 under 18 years.

The study involved more than 45,000 people, of which 14.6% 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 people with IBD who lived rurally and compared them with 2,302 people with IBD from urban areas.

“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.”

Dr. Martin Blaser — a professor of medicine at the New York University School of Medicine in New York City — and his 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 maternal parent.

The initial boost of microbes we have exposure to at birth is crucial in getting our immune system off to a good start.

In a 2017 study, Prof. Blaser and colleagues found that it is not the antibiotics as such that cause an increase in IBD risk. Rather, antibiotic use changes the maternal parent’s microbiome, which then passes 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 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 maternal parents 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.

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, epidemiologists, 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.