Microscopic Colitis and Pregnancy

By Wayne Persky

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For decades we've noted that pregnancy significantly affects the clinical symptoms of microscopic colitis (MC) patients. Many patients who are currently in a flare, tend to experience a remission as their pregnancy progresses. And occasionally, the reverse occurs. In other words, patients who are in remission, experience a relapse of symptoms as their pregnancy develops. Theories about why this happens have usually focused on hormonal changes that occur during pregnancy.

And indeed, the hormonal changes that occur with pregnancy are numerous and relatively complex. Beginning 6 to 12 days after fertilization, trophoblast tissue in embryos (this tissue will eventually be part of the placenta) produces the chemical human chorionic gonadotropin (hCG), which promotes the production of progesterone and estrogen until the placenta takes over. Production of hCG peaks at around 10 weeks. hCG frequently triggers the symptoms of morning sickness.

As the pregnancy proceeds, many additional hormones are eventually produced to enhance the development of the fetus. And soon after these hormonal changes begin, the symptoms status changes for many MC patients, so it seemed logical that the hormonal changes might be the primary reason for the sudden remission of symptoms for some patients, and relapse of symptoms for others.

Research published in 2015

noted that approximately 80% of IBD patients who become pregnant while their disease is in remission tend to remain in remission throughout their pregnancy and postpartum period (Hashash and Kanen, 2015).1 Furthermore, the authors pointed out that approximately one third of both ulcerative colitis and Crohn's patients who were not in remission when they became pregnant, went into remission after becoming pregnant.

As is virtually always the case, MC patients were not included in this study, nor were they included in the more recent study referenced just below. But note how similar the disease statistics cited by the studies seem to compare with the experiences of MC patients.

A recent research project made a rather surprising discovery.

This study of IBD patients found that significant changes that take place in the epithelial lining of the small intestine during pregnancy may be responsible for the cessation of clinical symptoms. According to the article, pregnancy and nursing trigger a doubling of the intestinal surface area of the villi of the small intestine (Onji, et al., 2024).2 Obviously, this change also doubles the ability of the small intestine to absorb nutrients (in order to meet the increased needs of both mother and baby).

This phenomenon is regulated by RANK/RANKL signaling.

The receptor activator of nuclear factor-κB and its ligand (RANK/RANKL) drives these structural changes. This system is regulated by pregnancy and lactation hormones, influencing intestinal stem cells to expand and reorganize the villi.

The process effectively doubles nutrient absorption.

Enlarged villi and increased intestinal surface area enhance the uptake of essential nutrients, including sugars, proteins, and fats. And slowed food flow through the intestine due to the structural changes further optimizes nutrient absorption.​

The research showed that in mice lacking the RANK/RANKL pathway, the failure of intestinal adaptation led to altered milk composition. Babies born to such mothers exhibited reduced weight and glucose intolerance under metabolic stress, indicating transgenerational health effects.

All mammals may have evolved with this survival enhancement.

This unique intestinal development appears to be a fundamental result of mammalian evolution. The intestinal adaptation represents an evolutionary strategy to support the survival and development of offspring. It's likely that similar changes occur across all mammalian species during pregnancy and lactation.

​And the intestinal change is only present during pregnancy and nursing.

The study showed that the intestinal expansion is reversed after lactation ends, providing a dynamic physiological adaptation, rather than a permanent change.​

Although this study was primarily conducted on mice, findings from human intestinal studies suggest that similar mechanisms should be applicable to humans.

And it's very likely that this is the primary reason why most pregnancies bring remission for active MC cases.

The evidence speaks for itself, because in most cases, the symptoms of MC are a result of the nutrient malabsorption issue associated with MC. So unless the malabsorption issues that lead to most of the clinical symptoms of MC are especially severe, doubling the surface area of the small intestine in which nutrients can be absorbed, should resolve the malabsorption issues for most MC patients.

But why do some MC patients who are in remission, suffer a relapse as their pregnancy develops.

Since this hasn't been specifically studied by any formal research projects, we can only speculate. However, it's well known that pregnancy itself is an inflammatory state due to the fact that the placenta produces cytokines that are capable of worsening the symptoms of IBD during pregnancy.

According to Doctor Daniel Stein, of RMA of New York, during pregnancy, the immune system must strike a delicate balance to support the developing baby while preventing its rejection as a foreign entity (Stein, 2020, October 26).3 One key component of this process involves T-lymphocytes (T-cells), which have distinct roles in the immune response. Cytotoxic T cells identify and destroy infected cells, while T-helper cells regulate other immune cells. These T-helper cells are further divided into subtypes with contrasting functions:​

TH1 cells produce cytokines that activate and enhance immune cell activity, promoting inflammation.
TH2 cells produce cytokines that suppress the immune response, reducing inflammation and preventing aggressive immune activity.

For a pregnancy to progress without complications, the balance between these cells is critical. A higher ratio of TH2 to TH1 cytokines is necessary to suppress excessive immune responses and avoid the rejection of the embryo.

Additionally, T regulatory cells (Tregs) play a crucial role in promoting the implantation of the embryo and facilitating the placenta's integration into the uterine wall. These cells help maintain immune tolerance to the fetus. Studies have shown that women with recurrent miscarriages or unexplained infertility often have reduced levels of T regulatory cells, highlighting their importance in supporting a healthy pregnancy.

This relatively critical balance between T cells may allow sufficient leeway for the inflammation level associated with pregnancy to overwhelm the state of remission associated with MC, to cause a relapse of MC symptoms. And although this hasn't been documented by research, it's possible that MC might have an effect on the balance between TH1 and TH2 cells under certain circumstances.

The prenatal supplement guidelines are especially important for MC patients.

The reason why they're especially important is because if we are reacting, we have a malabsorption problem, and even if we're in remission, we're on a restricted diet, which may result in the development of deficiencies in certain vitamins and minerals, if not properly supplemented.​

Adequate nutrition is critical for not only a developing fetus, but the mother-to-be, also. And this is often a problem for mothers who do not have an IBD, making proper supplementation especially important for MC patients. Magnesium is particularly important. Many of us struggle to keep our magnesium reserves at a safe level, and adequate magnesium is especially critical during gestation.

In fact, Dr. Carolyn Dean, author of "The Magnesium Miracle", suggests that increasing magnesium reserves early on during pregnancy can help to prevent morning sickness, although that opinion isn't shared by most physicians.

References

1. Hashash, J, G. and Kanen S. (2015). Pregnancy and Inflammatory Bowel Disease. Gastroenterology & Hepatology, 11(2), pp 96–102. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC4836574/

2. Onji, M., Sigl, V., Lendl, T., Novatchkova, M., Ullate-Agote, A., Andersson-Rolf, A., , , Penninger, J. M. (2024). RANK drives structured intestinal epithelial expansion during pregnancy. Nature, Retrieved from https://www.nature.com/articles/s41586-024-08284-1

3. Stein, D. E. (2020, October 26). The Immune System and Pregnancy: How Your Body Can Turn on Itself. RMA of New York, retrieved from https://www.rmany.com/blog/the-immune-system-and-pregnancy-how-your-body-can-turn-on-itself