Overview of the Gut Microbiome and Its Role in GVHD

By Elaine S. DeMeyer, RN, MSN, AOCN®, BMTCN® - April 19, 2023

Graft-versus-host disease (GVHD) is a common, potentially devastating complication of allogeneic stem cell transplant (allo-SCT) targeting the gut or gastrointestinal (GI) tract, particularly in acute GVHD. The intestinal or gut environment (often called the microbiota) plays a critical role in the risk of developing GI GVHD, infection, and poor outcomes. As more people learn about how microbes change in varying conditions, oncology nurses caring for patients with GVHD must better understand the gut microbiome and its role in GVHD.

What Is the Gut Microbiome?

With more information about overall health, people are learning about the role of a diverse microbiome in helping to digest food, regulate the immune system, and protect against other disease-causing bacteria. For example, patients may receive instructions from their primary care provider to add over-the-counter probiotics when taking antibiotics. Antibiotics work by killing bacteria. However, like chemotherapy that kills all rapidly dividing cells, antibiotics cannot distinguish between good and bad germs. As a result, they kill the gut’s healthy bacteria. Many providers believe that probiotic supplements during antibiotic treatment can minimize some side effects of antibiotic therapy, such as antibiotic-associated diarrhea.

All areas of the human body contain normal flora such as bacteria in the gut or skin. Flora is often taught in anatomy, physiology, and microbiology courses, as well as cancer nursing principles. The gut environment is home to trillions of microbes, or microscopic organisms that cannot be seen with the naked eye. Terminology can be confusing, so review the language here:

  • Microbiome: The term microbiome refers to “the collection of all microbes, such as bacteria, fungi, viruses, and their genes, that naturally live on our bodies and inside us.”
  • Microbiota: A similar term, microbiota refers to the collection of microbes in a specific environment, like the gut, so that “the microbiota comprises all living members forming the microbiome.”
  • Dysbiosis: This is an imbalance of the gut microbiome, which can lead to inflammatory bowel diseases, cancer, and other disorders.

What Is the Gut Immune Response in Acute GVHD?

Microbiota and the gut have a mutually beneficial relationship in healthy individuals. A mucosal layer remains intact, creating a barrier between the microbiota and intestines. The path of gut GVHD begins with damage to the intestinal mucosa and cross-talk between intestinal microbiota and the immune cells. Essentially, the imbalance of certain T-cells and inflammatory factors influence the microbiome. Below is an outline of how the pathway occurs:

  1. Conditioning therapy with chemotherapy and/or total body irradiation damages the intestinal wall.
  2. The injury exposes the macrophages to the bacteria in the microbiome.
  3. The immune response triggers cells to produce IL-12 to communicate with other immune cells, including T-cells that secrete messages to rev up the immune system.

Microbiota can modulate immune response. After the destruction of the intestinal barrier, bacteria and microbial metabolites move to the layer just below the epithelium to regulate the immune response.

Furthermore, a compromised microbiome before conditioning treatment and allo-SCT can worsen outcomes. Prophylactic antibiotics can damage the microbiome although used to treat infection or a prolonged immunodeficiency. In addition, supportive care drugs such as anti-emetics can contribute to gut damage.

Why Is the Microbiome Important in GVHD?

An imbalance in the microbiome, or dysbiosis, that disrupts the integrity of the mucosal barrier can have clinical significance in gut GVHD. Changes in the microbiota resulting in lower intestinal diversity of allo-SCT recipients can:

  • Increase risk of developing gut GVHD. Microbiome diversity continues to decline after allo-SCT, contributing to the increased probability of gut GVHD.
  • Increase severity of gut GVHD. Several factors influence the severity of GVHD, with disruption in the microbiome being a contributing factor.
  • Result in poorer outcomes. Patients may have higher rates of infection and infectious complications and a higher risk of transplantation- or GVHD-related mortality.

Studies show that better microbiome diversity in patients receiving allo-SCT can lead to improved outcomes, “Increased microbial diversity from low to intermediate to high increased 3-year overall survival rates in recipients of allo-SCT from 36% to 60% to 67%, respectively.”

Microbial health pre-GVHD onset is linked with lower GVHD-related mortality and lengthened survival. Oncology nurses must have a foundational understanding of the gut microbiome and its role in GVHD, particularly gut GVHD. Overall, there is growing evidence about the importance of the microbiome in maintaining health. Newer research suggests that the intestinal microbiome may be a biomarker for GVHD outcomes. Ongoing studies are exploring strategies to preserve and restore a healthy microbiome in patients receiving allo-SCT.



Microbiome Definition Re-Visited: Old Concepts and New Challenges

Allogeneic Hematopoietic Cell Transplantation, the Microbiome, and Graft-Versus-Host Disease

Microbiome-Intestine Cross Talk During Acute Graft-Versus-Host Disease

Interplay Between the Intestinal Microbiota and Acute Graft-Versus-Host Disease: Experimental Evidence and Clinical Significance