I think we’ve all heard the Pepto Bismol® jingle…you know the one… “If you have nausea, heartburn, indigestion, upset stomach, diarrhea…” (I bet you just sang that as you read it, and I’m sorry…it’ll be stuck in your head all day now!)

For people who haven’t had a stem cell or bone marrow transplant, these symptoms may signal a passing stomach bug or a bout of food poisoning. But for survivors of stem cell transplants, these kinds of symptoms can be signs of something much more serious — GVHD of the gastrointestinal (GI) tract.

The GI tract refers to our entire digestive system, starting with our mouth and ending at our anus, encompassing all the organs between the two. When GVHD sets up shop in the GI tract, the esophagus, stomach, intestines, and colon may all come under attack, or one area may be more adversely affected than the others.

Symptoms of GI GVHD

People with GVHD of the GI tract can have a variety of uncomfortable and, let’s be honest, life limiting symptoms. That’s true with any type of GVHD, but GVHD of the gut can be especially troublesome and dangerous.

The dysfunction that results from GVHD “attacking” the esophagus, stomach, intestines, and/or colon can cause the full spectrum of gut upset, things like:

• Nausea or vomiting
• Diarrhea, which can be watery or bloody, or may contain mucus
• Abdominal pain or cramping
• Unintentional or excessive weight loss
• Feeling full, or feeling bloated
• Little or no appetite
• Indigestion or heartburn
• Undigested food in stools, or greasy or bloody stools

While there are other conditions that can look like GVHD of the gut — an infection or virus, food allergy, or medication reaction, for example — if you’re a transplant survivor, it’s extremely important to tell your doctor right away about any GI symptoms you experience, so they can determine if it’s GVHD. If it is, the sooner you start treatment the more effective it will be.

Diagnosing GVHD of the Gut

Because GI GVHD can sometimes mirror other health problems, doctors must use internal diagnostic tests to visualize your stomach and intestines and take tissue samples. This is usually done through an EGD (esophagogastroduodenoscopy) and colonoscopy, or sigmoidoscopy.

During an EGD, a thin, flexible tube with a camera on the end is inserted through your mouth down to your stomach and small intestine, giving your doctor a clear picture of what’s happening inside those organs. A colonoscopy does the same thing, but from the opposite end — a tube with a camera is inserted through your rectum to allow the doctor to see inside your large intestine. Tissue samples can be taken during either test to be examined more closely under a microscope, too, which helps the doctor diagnose whether your symptoms are being caused by GVHD or something else.

GI GVHD Treatment

Treatments for GI GVHD aim to control and prevent symptoms, and resolve them when they occur.

Systemic corticosteroids are the first line of defense — usually an oral medication or injection that suppresses the body’s entire immune system, calming the overactive inflammatory response behind GVHD. Prednisone is an example of a systemic steroid that may be familiar to you. Topical steroids (steroids that are applied to your skin) are also sometimes given orally in pill form as well, to coat the inside of the stomach. Beclomethasone in corn oil and budesonide pills are examples.

ECP — or extracorporeal photopheresis — is sometimes used to help manage GI GVHD, as well as many other forms of GVHD. ECP is a type of light therapy that calms overexcited immune cells and lessens the exaggerated immune response that gives way to GVHD. Photosensitizing chemicals are combined with a patient’s blood and then exposed to ultraviolet light to achieve this.

Beyond that, anti-nausea medications — like Zofran® — and medications to help control diarrhea, like Imodium® or Lomotil®, can be very helpful, too. If your pancreas isn’t working properly, you’ll need to take enzymes before meals to help your body break down your food so you can absorb the nutrients as well.

In conjunction with these treatments, your doctor may put you on a restrictive diet designed to help control symptoms of GI upset before slowly reintroducing foods in a methodical way. This often progresses from eating and drinking nothing (during which time you will likely be given nutrients via an intravenous (IV) infusion) to a liquid diet, followed by easily digestible solid foods and finally a return to a regular diet recommended by your doctor and nutritionist. Here’s an example of what that progression might look like from Roswell Park Comprehensive Cancer Center.

The Gut Microbiome

You know those plot twists in suspense movies that totally throw you for a loop? GI GVHD has one of those. Here goes…not only can your gut be the target of GVHD, it might also actually trigger it. Crazy, right?

Here’s the cliff note version of how it works…our GI tract is home to billions of bacteria, both helpful and harmful, that are all together known as our microbiome. In a healthy GI tract, the good guys keep the bad guys from getting out of control, stopping them from wreaking havoc in our bodies.

If this delicate balance is thrown off, it can contribute to the development of many different diseases, including (you guessed it!) GVHD. Researchers are now discovering that the make-up of a patient’s pre-transplant microbiome can, in fact, influence GVHD outcomes — some bacteria can keep the disease at bay while other types of bacteria can actually play a role in triggering the disease.

Chemotherapy and radiation pre-transplant can also sometimes damage a patient’s intestinal wall, which sets the stage for the “bad guys” to do their worst, triggering the inflammatory cascade that leads to GVHD.

It’s a fascinating area of research that you can learn more about in these articles from the Fred Hutch Cancer Center:

https://www.fredhutch.org/en/news/center-news/2023/07/koyama-hill-gvhd-suppressor-bacteria.html

https://www.fredhutch.org/en/news/center-news/2019/09/transplant-gut-gvhd-microbiome.html

And if you’re interested, here’s a presentation from nbmtLINK that talks about the subject more in depth, too.

Clinical trials are underway to determine the effectiveness of things like fecal transplants and plant-based diets to promote a healthy microbiome and gut bacteria diversity.

Nutrition and GI GVHD

People with GI GVHD are often advised to avoid certain foods and food groups that may make symptoms worse — things like spicy foods; high-fat, greasy, or fried foods; artificial sweeteners; dairy; citrus fruits and juices like oranges, lemons, tomatoes, etc. (because they’re acidic and irritating to the stomach); and high fiber foods, like nuts and seeds, whole grain products, popcorn, and the like, which can worsen diarrhea and stomach cramping.

It’s important to work closely with your health care team and nutritionist to determine which foods do or don’t work for you, and how much of each macronutrient (i.e. protein, fat, and carbohydrates) you should be eating to maintain muscle mass and stay at a healthy weight. Unfortunately, some of the foods you loved before GI GVHD may no longer be appealing or sit well with you now. And it may be hard to maintain your weight between having little or no appetite and experiencing stomach upset.

At the beginning of your disease, your doctor will likely recommend a restrictive diet that will control your symptoms, before more foods are progressively added in over time.

If you’re struggling to maintain your weight, here’s a few tips taken from BMT Infonet that may be helpful. Make sure you only eat foods that agree with you, though, and avoid any recommendations that conflict with advice you’ve been given by your doctor.

• Eat small high-calorie meals frequently throughout the day. Examples of high-calorie, nutrient dense foods are full-fat, pasteurized dairy (if you can tolerate it…some people with GI GVHD can’t, unfortunately), eggs, avocados, fatty fish, nuts and nut butters (again, if they agree with you), hummus, potatoes, dried fruit, olives, etc.
• Try adding protein supplements / powder (like Promod® or Unjury®), or protein shakes (like Ensure®, Carnation®, or Boost®) to your routine, if your doctor and nutritionist approve.
• Use oils and fats when you cook your food instead of nonstick sprays. Avocado and olive oil are great “healthy” oils to try, in addition to butter and ghee.

Your doctor may also be able to prescribe you medication to stimulate your appetite, if needed.

If you want to learn more, check out this research article on nutrition and its connection to GVHD.

Combating Symptoms of GI GVHD

When you have GI GVHD, diarrhea isn’t just a nuisance that can keep you from enjoying your life (although it certainly does that) — it can also become dangerous quickly, as metabolic and nutritional deficiencies can develop in the blink of an eye. That’s why it’s incredibly important to report any change in your bowel habits to your doctor immediately, so they can advise you on the best course of action.

BMT Infonet also suggests the following if you’re suffering from diarrhea (again, please follow the recommendations of your doctor and/or nutritionist first and foremost):

• Eat smaller meals, and drink fluids in between meals rather than with them.
• Increase your fluid intake.
• Try hard cheeses, peanut butter, and oatmeal — they’re binding.
• EAT foods high in potassium and low in insoluble fiber, things like ripe bananas, skinless potatoes, baked chicken and fish, lean beef, eggs, cooked veggies (but not cauliflower, cabbage, broccoli, or beans), canned fruit/applesauce, white bread, and white rice. In addition to water, consider hydrating with Gatorade® or Pedialyte®.
• AVOID high fiber foods like nuts and seeds, popcorn, fruit with the skin still on, raw veggies, whole grain breads and cereals, and bran. Also avoid things that can cause gas and cramps, like cruciferous veggies (broccoli, cabbage, cauliflower, etc.), gum, carbonated drinks, spicy foods, and foods with thick gravies and sauces.
• AVOID caffeinated drinks like coffee, pop, and tea, and chocolate and dairy products (unless they’re lactose-free), too.
• Steer clear of medications like Immodium® unless approved by your doctor — if you have a colon infection, they might make it worse.

On the opposite end of the spectrum from diarrhea, constipation caused by GI GVHD causes its own set of problems, and comes with a very different set of recommendations from nutritionists.

If you’re constipated, make sure you alert your doctor and get their opinion on trying the following:

• Eat high fiber foods, like well-washed raw fruits and vegetables (as long as you’re not neutropenic [i.e. have a low neutrophil count] — people with neutropenia shouldn’t eat raw produce), dried fruit, and whole grain cereals and breads.
• Drink plenty of fluids, too, especially warm beverages. Stewed prunes or warmed prune juice are great options.
• Go for a walk or perform other light exercises, especially after you’ve eaten, to encourage GI motility.

You can also talk to your doctor about taking laxatives, fiber supplements, or stool softeners if the problem persists, too.

The Bottom Line

GI GVHD can be hard to manage, and symptoms like vomiting and diarrhea aren’t just life-limiting, they can become dangerous when nutrient and fluid levels in the body are compromised. If you’ve had a stem cell transplant, it’s important to report any GI related symptoms to your health care team immediately so they can help you determine what to do. If it’s GVHD, systemic corticosteroids will likely be prescribed, and other treatments are available to help, like anti-nausea and anti-diarrheal medications. Your doctor may also want you to follow a restrictive diet to get symptoms under control before reintroducing foods.

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Sources

1. https://bethematch.org/materials-catalog/items/fast-facts—ghvd-of-thestomach-and-intestines/?pid=15558
2. https://bmtinfonet.org/transplant-article/liver-gastrointestinal-tract-and-chronic-gvhd
3. https://www.fredhutch.org/en/news/center-news/2023/07/koyama-hill-gvhd-suppressor-bacteria.html
4. https://www.fredhutch.org/en/news/center-news/2019/09/transplant-gut-gvhd-microbiome.html
5. https://bmtinfonet.org/sites/bmtinfonet.org/files/2021%20FINAL%20Nutrition%20Brochure.pdf
6. https://bmtinfonet.org/video/graft-versus-host-disease-gastrointestinal-tract-and-liver-1
7. https://www.roswellpark.org/pted.php?pemID=PE657o