Photo Credit: Courtesy Bar Ilan University
International microbiome specialist Dr. Omry Koren of the Azrieli Faculty of Medicine of Bar-Ilan University.

Inflammatory bowel disease (IBD) is an umbrella term used to describe disorders such as ulcerative colitis and Crohn’s disease, which involve chronic inflammation of the digestive tract. IBD affects millions of people worldwide.

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, there’s good news in store. A recent international study, published in the journal Gut (Modulation of cytokine patterns and microbiome during pregnancy in IBD), shows that pregnancy is safe and potentially beneficial for women with IBD.

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On Thursday, Dr. Omry Koren, of the Azrieli Faculty of Medicine of Bar-Ilan University, will present the research findings at The Esther and Haim Carasso Microbiome Israel Workshop: “From Bench to Bedside”, a conference focusing 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, 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 acquired 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, 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 (richness). The comparison of IBD with healthy microbiomes revealed 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 Dr. Koren, Director of 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 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 Department of Mathematics, 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,” says Dr. Koren. “From an immunological and microbiological viewpoint, pregnancy in patients with IBD is beneficial and can be safely recommended.”

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