Inflammatory bowel disease (IBD) is a collection of gastrointestinal diseases that involve chronic inflammation of the digestive tract. The most common of these disorders is ulcerative colitis, which is slightly more common in males, while Crohn’s disease is more frequent in women.

Ulcerative colitis causes long-lasting inflammation and sores (ulcers) in the innermost lining of the large intestine (colon) and rectum; Crohn’s is characterized by inflammation of the lining of the digestive tract, which often spreads deep into affected tissues. Both chronic conditions usually involve severe diarrhea, abdominal pain, fatigue, and weight loss, and they can be debilitating and sometimes lead to life-threatening complications.

In the US alone, about 1.6 million people, including 80,000 children, currently have IBD, a rise of about 200,000 since the last time it was checked in 2011. As many as 70,000 new cases of IBD are diagnosed in the US each year. There are 80,000 children in the US with IBD.

IBD affects women in unique ways. IBD can cause:

IBD rates are also on the rise in Israel, with nearly 40,000 patients here diagnosed with it, compared to just 30,000 about a decade ago. 

Doctors still don’t know the exact cause of IBD; previously, diet and stress were suspected, but now doctors it is believed that these factors may aggravate but don’t cause IBD. One possible cause is an immune system malfunction in which this protective mistakenly regards cells in the digestive tract as an “enemy” and attacks them. Heredity also seems to play a role in that IBD is more common in people who have family members with the disease, but still, most IBD patients don’t have such a family history. Most people who develop IBD are diagnosed before they’re 30 years old, but some people don’t develop the disease until their 50s or 60s.

Women suffering from IBD are at a higher risk for iron-deficiency anemia than their healthy peers. They also suffer from more menstrual symptoms. Women in their fertile years who have IBD are more likely to experience premenstrual symptoms, such as headache and menstrual pain and have trouble getting pregnant, especially during a flareup of the disease. 

Although Caucasians have the highest risk of the disease, it can occur in any race. Jews of Ashkenazi descent have a higher-than-normal risk of IBD. Cigarette smoking is the most important controllable risk factor for developing Crohn’s disease. Contracting colon cancer is a complication of ulcerative colitis and Crohn’s, as is primary sclerosing cholangitis, in which inflammation causes scars within the bile ducts, eventually making them narrow and gradually causing liver damage.

Among female patients with IBD, a common concern is how pregnancy will affect their disease course, and conversely, how the disease will affect their pregnancy and fetal health.  For these women, however, there’s good news in store. A recent international study, recently published in the journal Gut, shows that pregnancy is safe and potentially beneficial for women with IBD. 

On Thursday, December 12, Dr. Omry Koren, of the Azrieli Faculty of Medicine of Bar-Ilan University in Ramat Gan near Tel Aviv will present the research findings at the Esther and Haim Carasso Microbiome Israel Workshop. Titled “From Bench to Bedside,” the event will focus on new insights into the microbiome. Koren, an international specialist in the microbiome during pregnancy, and team led the study in cooperation with specialists in the immunology of IBD in pregnancy from University Medical Center in Rotterdam in the Netherlands. 

As cytokine levels (a measurement of inflammation patterns) are known to behave differently in patients with and without IBD, the researchers compared cytokine patterns and faecal microbiome in pregnant patients with IBD and in pregnant healthy controls. The samples were chosen from a cohort of 46 women with IBD (31 with Crohn’s disease and 15 with ulcerative colitis) and 170 healthy control individuals at various points in time before, during and after pregnancy.  

Healthy women showed pregnancy-associated changes in serum cytokine levels during the trimesters of pregnancy that are not seen in pregnant patients with IBD.  In pregnant patients with IBD, these levels decreased significantly after conception. This suggests that pregnancy reduces immunological parameters of inflammation in patients with IBD. 

During pregnancy itself, serum cytokine levels in patients with IBD remained relatively stable, with some even lower compared with healthy controls, throughout the three trimesters. Overall, the researchers concluded, it seems that the immunological state of patients with IBD improves in pregnancy. In addition, although intestinal microbiome diversity was reduced in patients with IBD compared with healthy women before and during early pregnancy, it normalized during middle and late pregnancy. 

One of the main microbiome characteristics observed in both disease and pregnancy is lower bacterial diversity. The comparison of IBD with healthy microbiomes showed that the IBD microbiomes were less diverse and more similar between patients than the healthy controls. This trend of lower diversity in patients with IBD has been previously reported and was expected. 

“To our surprise, however, we observed that the IBD microbiomes were more similar to one another, suggesting that the same species disappear during disease from the majority of patients,” said Koren, ho heads the Microbiome Research Lab at Bar-Ilan University’s Azrieli Faculty of Medicine. “We have previously demonstrated that during pregnancy in healthy females, microbial diversity decreases. The fact that bacterial diversity differed between patients with IBD and controls during early pregnancy but decreased at later gestational times indicates that pregnancy in IBD is not followed by an additional loss of diversity on top of the already altered microbial composition in these patients.”

The same results were determined for both Crohn’s and CD and UC, meaning that the immune system did not undergo change, while the microbiome did.   UC and CD had different microbiomes before and during pregnancy, whereas when pregnancy progressed, a decrease in microbiome diversity was seen in patients with both disorders, which is what is known to occur in regular pregnancy with no IBD. Prof. Yoram Louzon, of Bar-Ilan University’s mathematics department, helped create a mathematical dynamic for understanding how changes at the beginning of pregnancy influence microbiome and cytokine changes at the end of pregnancy.

Pregnancy affects many physiological processes that are deregulated in IBD, but until now little has been known about immune and microbial signatures in patients with IBD during pregnancy.  

“This is the first time that samples have been compared to healthy controls before, during and after pregnancy,” concluded. Koren. “From an immunological and microbiological viewpoint, pregnancy in patients with IBD is beneficial and can be safely recommended.”