Graft vs Host Disease and the Gut Microbiome

Anyone reading had to have an allogeneic hematopoietic cell transplantation (HCT) or know someone who has had one? 

This is a standard treatment for people diagnosed with leukemia, lymphoma, and aplastic anemia. Basically, allogeneic HCT is a donation of hematopoietic stem cells from a healthy donor with similar and specific genetics to the recipient.

Graft vs host disease (GvHD) is a common complication of HCT where the recipient’s immune system sees the donor cells as intruders and fights against the cells. This results in debilitating symptoms such as diarrhea, nausea, vomiting, abdominal pain/cramping, oral ulcers, and sclerosis of the skin. GvHD is a common cause of death in people receiving allogeneic HCT, affecting approximately 30-70% of people who receive HCT.

Typically, people who undergo HCT also take heavy doses of antibiotics to keep pathogenic bacteria down and allow the new cells to “take or graft” into the host body. During this time, people who have received HCT are at an increased risk for developing illnesses because their bodies are so susceptible to pathogens (viruses and bacteria). The underlying causes of GvHD have not been quite identified and possible prevention methods are currently being researched- of course, the gut microbiome is involved (SURPRISE!!)

Antibiotic therapy is part of current practice, however, the type of antibiotics used is still varied and studies are working to identify if certain antibiotics are better than others. Some are non-absorbable for complete gut decontamination and some antibiotics are used to allow for selective gut decontamination.

• Several studies have identified that anti-anaerobic antibiotic therapy (metronidazole) is associated with a reduction in acute GvHD but no additional trials have been published at this time.

Researchers are working to identify if certain bacterial populations are associated with increased and decreased risks of GvHD.

• Low gut bacterial diversity has been associated with increased GvH-related mortality. One study found that loss of bacterial community diversity in stool during engraftment after HCT was associated with reduced overall survival and increased transplant-related mortality.
• The Blautia bacterial species may be associated with the reduction of GvHD-related mortality in humans
• Probiotic strain Lactobacillus rhamnosus GG was associated with reduced GvHD and improved survival in mice – more studies are needed in humans to see the effects
• Lower levels of bacteria from the Firmicutes phylum have been associated with GvHD risk
• Lower levels of Bacteroides and Parabacteroides species were observed in people who developed acute GvHD.
• Lower levels of short-chain fatty acids in stool samples from subjects with GvHD may indicate lower bacterial diversity

As mentioned in other articles and posts on Foodguides, the gut microbiome plays an important role in not only gut health but overall immunity and disease process too. Therefore, it is important to look at this as a possible route for preventing and treating GvHD in people who receive allogeneic HCT. It will be exciting to see what news continues to develop in this field.

So from a nutrition standpoint, what can you do to manage GvHD?

• Follow safe food-preparation guidelines

• If you are experiencing nausea, vomiting, or diarrhea follow a bland, low-fiber diet to manage symptoms. Avoid foods that are acidic, spicy, and have seeds and tough skins. Sip on plenty of clear liquids and try to eat small amounts more frequently throughout the day. Limit lactose intake.

• If you develop mouth sores use the following 3-4 times per day to clean your mouth:
• ¾ tsp salt + 1 tsp baking soda + 32 oz sterile water

Talk with a registered dietitian for more information- it is important to be monitored closely as people suffering from GvHD are at increased risk for malnutrition and further nutrition interventions may be indicated.

1. _{Fredricks, D. N. (2019). The gut microbiota and graft-versus-host disease. Journal of Clinical Investigation, 129(5), 1808–1817.}
2. _{Payen, M., Nicolis, I., Robin, M., Michonneau, D., Delannoye, J., Mayeur, C., Kapel, N., Berçot, B., Butel, M.-J., Le Goff, J., Socié, G., & Rousseau, C. (2020). Functional and phylogenetic alterations in gut microbiome are linked to graft-versus-host disease severity. Blood Advances, 4(9), 1824–1832.}
3. _{Hemopoietic Stem Cell Transplant- Nutrition Intervention. - Nutrition Care Manual. (n.d.). Retrieved March 20, 2023.}