The past,the present,and the future in the gastrointestinal health of women: An interview with Dr Jacqueline L Wolf

• Q Professor Wolf, what first sparked your interest in the field of women’s health, and more specifically women’s gastrointestinal health?

When I first became a gastroenterologist there were very few women in what was considered a man’s field. Because of my gender, women with gastrointestinal (GI) issues sought me out. In a very short time I appreciated the differences in the manifestation and frequency of GI problems in women compared to men. Furthermore, the chief of obstetrics–gynecology (OB-GYN) announced one day to his department that henceforth I was to be the GI consultant for all of the pregnant women with GI complaints. Suddenly, overnight I was the expert. With over 10,000 deliveries per year, I developed a vast exposure to pregnant women with GI complaints and liver disease in pregnancy who needed safe and effective diagnoses and management.

• Q What have been your most important/interesting research findings in this area?

Discovery of something new or an answer to a puzzling question is exhilarating. For me, this can be an answer to a basic research question or an elusive answer to a patient’s medical problem.

In the first part of my career, I studied how a virus could cross the GI track and then interact with the gut-associated lymphoid tissue (GALT), a question of major importance for protection from and treatment of diarrheal and other viral diseases in which the organism enters through the gut. In mice, I discovered that reovirus crossed the intact intestinal mucosa through the intestinal M cell overlying Peyer’s patches where it then was in close proximity to the GALT where it could interact and affect the mucosal immune system. ¹

In the second part of my career, I have written reviews on GI and liver conditions in pregnancy that have been important guides for clinicians to help improve the GI health of women in pregnancy, while providing safe therapy for the offspring.^2,3 Application of the same rational method of inquiry used in my basic research to pursue an elusive answer to a stubborn clinical question has made a difference to the lives of many people, a few of whom have shared their stories in the lay media.^4,5

A patient-driven study just completed on the GI problems in people with Marfan and Ehlers Danlos Syndrome should lead to new insights into their GI problems and to new clinical studies to improve the lives of women and men with these conditions.

• Q What are the main obstacles that clinicians such as yourself face in effectively treating GI disorders?

I believe there are four main obstacles in treating GI disorders.

The first obstacle is obtaining all of the pertinent information from an individual. Frequently stomach ailments are shrouded in secrecy and shame and abuse and stress are hidden. Women do not want to admit the foul odor in the room is from their uncontrollable flatus; that they wear an adult diaper because they can’t make it to the toilet in time; or that they can’t go out with friends or family because almost all food makes them feel sick. Shame about financial resources resulting in the inability to obtain healthy food choices or medications may not be communicated, leading healthcare providers to misunderstand the etiology(ies) of symptoms and the poor response to treatment. Past abuse may contribute to the avoidance of undergoing a colonoscopy to detect polyps or cancer.

The second obstacle is fragmentation of medical care. This includes having a physician caring for a patient during an acute illness who does not know the full history. Communication between healthcare providers is often lacking. Online and written medical records from different institutions are often not accessible by all physicians caring for a patient and too cumbersome to review to get a holistic picture of a patient.

The third obstacle is time. Because of the push to see more and more people in a day, the time allotted to a visit may lead to a narrow focus on the current GI issues and not a broader investigation of other pertinent factors that may impact the GI condition.

The fourth obstacle is compliance of an individual with treatment recommendations. A mother may not have time to cook two separate meals, exercise daily, work, and take her children to all of their activities. With her mind cluttered with so much to do, she may not remember to take her medications properly. She may need to make choices due to financial constraints–eat a healthy meal or take one or more of the prescribed medications. She may choose a medication to take based on her symptoms of the day and/or a poor understanding of her condition and why she is taking a medication.

• Q What, in your opinion, have been the most major breakthroughs in the diagnosis of GI disorders in women over the last 10 years?

• For diagnosing constipation. Recognition of obstructed defecation and the appropriate testing: anorectal motility and defecography;

• For diagnosing celiac disease. Improved and sensitive blood tests—IgA tissue transglutaminase antibody, deamidated gliadin peptide (DGP) antibodies (anti-DGP), IgA or IgG;

• For general diagnosis. Improvement in magnetic resonance imaging (MRI) for liver, pancreas, and biliary disease, and activity of inflammatory bowel disease (IBD);

• For diagnosing liver scarring. Fibroscan;

• For diagnosing bleeding sites in the small bowel, active IBD, and colon polyps. capsule endoscopy;

• For Clostridium difficile diagnosis. Polymerase chain reaction (PCR) of the stool.

• Q And in what major ways has management/treatment of GI disease in women progressed?

• Irritable bowel syndrome (IBS) and chronic idiopathic constipation occur approximately two to three times more frequently in women than in men in the Western world. New medications to treat these conditions are now or soon will be in wide use. For IBS with constipation and chronic idiopathic constipation lubiprostone, which activates the CIC-2 chloride receptor on the apical surface of epithelial cells and linaclotide, a selective agonist at the guanylate cyclase-C receptor on the luminal surface of intestinal enterocytes has been developed. For IBS with diarrhea eluxadoline, a mixed µ- and κ-opioid receptor agonist/δ-opioid receptor antagonist was recently approved by the Food and Drug Administration (FDA) in the United States.

• Dyssynergic defecation, increasingly recognized as a problem affecting predominantly women, is treated by physical therapy eliminating the need for more and more laxatives.

• Healthcare providers are more likely to listen to the “patient.” Women with abdominal pain with or around the menstrual period are now less likely to be told, “Dear, you just will have to live with it. That is what happens when you are a woman.” Endometriosis and hormonal effects on the bowel are more readily recognized and better treated.

• The safety of drugs in pregnancy and the effect of pregnancy on medical conditions are further being identified.

• Medications curing hepatitis C are in widespread use. Hopefully if the price of the drug comes down and more global use occurs, hepatitis C will become a rare acute not chronic disease.

• New biologic medications have been developed for curing or improving symptoms in IBD.

• Q What role, if any, do you think complementary and alternative medicine such as acupuncture plays in effective management of GI diseases?

Complementary medicine is becoming mainstream. A major area of research not only in GI conditions but also in obesity and mental health is the gut microbiome. The gut microbiome is very diverse and has been shown to vary in those people with and without IBS and IBD and in obese versus lean animals, in which it can be changed to impact weight gain. This provides the opportunity for directing specific probiotics to individuals to improve their conditions. ⁶ In IBS, the use of peppermint oil for cramping has joined mainstream therapy. Acupuncture does not appear to be a beneficial therapy for IBS since a controlled trial in IBS patients showed that sham acupuncture worked as well as acupuncture. ⁷ Further trials are needed to determine the role of acupuncture in other GI conditions. Cognitive therapy and hypnosis have been effective in some studies for the treatment of IBS. Dietary therapy plays a major role in the management of many GI conditions: celiac disease, IBS, and in some people IBD.

• Q How does pregnancy affect symptoms and management of IBD? And what about that of GI disease in general?

Pregnancy may have profound effects on pre-existing diseases as well as predisposing women to specific disorders. Management and treatment of GI ailments in pregnant women require special attention to the safety and effectiveness of diagnostic tests and therapies for the mother and fetus.

In IBD, conception and pregnancy outcome may be impacted by disease activity, type and extent of IBD, history of abdominal surgery, and medications. Women’s overall fertility rate is normal but alteration may occur with active Crohn’s disease, malnutrition or if blocked fallopian tubes. Fertility is decreased after ileal pouch anal anastomosis. A good pregnancy outcome is expected if the disease is inactive at conception. Many of the complications during pregnancy come from women discontinuing effective medications.

Most medications for IBD are safe in pregnancy. 5-Aminosalicylic acid (5-ASA) medications and probably 6-mercaptopurine (6-MP) and azathioprine should be continued. The use of antitumor necrosis factor medications is safe, but since infliximab and adalimumab will cross the placenta in the third trimester many clinicians will stop the infliximab in the third trimester and the adalimumab at 36-38 weeks if the mother has stable disease, resuming treatment post partum. In addition, these babies should receive NO live virus vaccines for the first 7–9 months of life. In Crohn’s disease, vaginal delivery is the delivery type of choice except for obstetrical reasons to the contrary and when active perianal disease is present. Risk of pre-term delivery is increased.

Other common conditions increased in pregnancy are nausea and vomiting, gastroesophageal reflux disease (GERD), constipation, and gallbladder sludge/gallstones. Nausea and vomiting of pregnancy (NVP) and/or heartburn occur in 95% of pregnant women. Nausea does not just occur in the morning as 33% of women have nausea throughout the day. ⁸ GERD occurs in 40%–80% of pregnant women. Constipation may occur de novo or may increase in severity during pregnancy. If lifestyle changes fail for these conditions, further therapies should consider the safety and effectiveness in mother and fetus. ²

• Q Where do you see the field of GI health in general heading over the next 5–10 years? What do you think should be the most important aspects of research in this area to prioritize?

Over the next 5–10 years I expect research may turn to the gut as the center that keeps the body healthy. The research on the gut bacteria is burgeoning. I anticipate that research well be directed at modifying the gut bacteria in a personalized way with fecal transplants and probiotics to improve GI health and possibly to reduce the risk of obesity, improve mental health, improve musculoskeletal health, and perhaps improve the health of other organ systems.

Treatment of diseases will likely be personalized. New evidence suggests that treatment of some cancers depends on the genetics of the cancer and the individual with the cancer. Personalized medicine may help determine the best treatment and reduce suffering and cost from unsuccessful therapeutic interventions.

I expect new vaccines will be developed to decrease the frequency of infectious diarrheal diseases that kill one in nine children under the age of 5 worldwide. Funding for vaccination development is important for global health. We are expecting a vaccine for C difficile, which may diminish the toll of this serious condition that disproportionally affects women after the age of 50.

Improving on stool tests for detecting colon cancer and precancerous lesions in IBD and further improvement of blood tests to detect people with IBS, IBD, or cancer may help decrease more invasive and expensive tests.

Minimally invasive surgery for appendectomy and other operations via endoscopic procedures (Natural Orifice Transluminal Endoscopic Surgery (NOTES)) will likely become more common as will endoscopic therapies for weight loss. These strategies may greatly reduce healthcare cost.