Graft-versus-host disease (GVHD) in the gut is a common complication after a stem cell transplantation (SCT) using donor cells (allogeneic SCT). Gastrointestinal (GI) GVHD, more commonly called gut GVHD, can damage both the upper and lower GI tracts, making it difficult for patients to eat and digest foods and liquids. Oncology nurses work closely with dietitians to help patients follow a special gut GVHD diet and nutritional supplement with enteral nutrition (EN) or total parenteral nutrition (TPN).
What Is the Role of Nutrition in GVHD?
Lesley B. Klein, MS, RDN, LDN, from the Sylvester Comprehensive Cancer Center at the University of Miami, said during her Nutrition Post Transplant presentation at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR that 3 critical components interact with each other and can result in deterioration of the patient’s overall state and well-being:
- Weight loss
- Impaired physical performance
- Systemic inflammation
These 3 elements can cause decreased quality of life, increased treatment toxicity, fewer treatments or treatment interruption, and ultimately a poorer prognosis in all patients with cancer. General concepts of the ESPEN (European Society for Clinical Nutrition and Metabolism) guidelines on nutrition in the cancer patient can apply to patients living with GVHD because both acute GVHD (aGVHD) and chronic GVHD (cGVHD) contribute to all 3 conditions.
Although there are several studies on nutrition in aGVHD, there is a lack of information about nutritional support in cGVHD. For example, in one literature search of 321 nutrition studies, 75% focused on aGVHD only.
How Does GVHD Affect Nutrition?
Both aGVHD and cGVHD result from complex mechanisms involving inflammation. Although the etiology of aGVHD is not the same as cGVHD, experimental models suggest that the initial phase of both aGVHD and cGVHD begins with damage of host tissues by the conditioning regimen and the resulting release of inflammatory cytokines. The inflammation of the gut can contribute to multiple symptoms and affect bowel function and overall health status.
Although there are several symptoms of gut GVHD that can affect nutrition, here are a few key conditions:
- Oral cGVHD: mouth sores, xerostomia, dysgeusia (taste changes)
- Upper GI GVHD (both aGVHD and cGVHD): anorexia, bloating, nausea/vomiting,
- Lower GI GVHD (both aGVHD and cGVHD): abdominal pain or cramps, ileus, watery or bloody diarrhea
In addition, fatigue, weakness, or mental health issues, such as anxiety or depression, can affect a patient’s nutritional status.
Why Use the Gut When Patients Have Gut GVHD?
Dietitian Klein emphasized, “If the gut works, use it! Due to emerging data regarding the gut microbiome as a key component of the human immune system and its link to reduced GVHD, you will likely see more tube feeding [enteral nutrition] in the future.”
Several studies suggest that intestinal dysbiosis (an imbalance in bacterial composition) contributes to the progression of gut GVHD. As a result, several studies are ongoing to better understand the role of the intestinal microbiota as a potential treatment target with dietary therapy. Enteral nutrition (EN) promotes the recovery of gut microbiome homeostasis (balance).
Is Enteral or Parenteral Nutrition Best?
A meta-analysis comparing clinical outcomes between patients receiving EN and those receiving total parenteral nutrition (TPN) showed reduced incidence rates in aGVHD overall, grades III-IV aGVHD, and gut aGVHD with EN. The better outcomes with EN are thought to be from:
- Gut barrier function
- Ability to balance the gut microbiome
In a retrospective review of 228 pediatric patients, aGVHD was seen in 25% of patients receiving TPN and 9% of non-TPN patients. In addition, sinusoidal obstruction syndrome (SOS) occurred in 13% of patients receiving TPN compared with no patients receiving EN. Therefore, TPN may be a disadvantage over EN since EN reduced the incidence of aGVHD and promoted faster platelet engraftment.
How Will Transplant Teams Use EN to Manage GVHD?
Researchers are exploring various strategies to modulate the gut microbiome. Interventions are preemptive (proactive) and therapeutic (reactive).
- Preemptive: EN, prebiotics, probiotics, fecal microbiota transplantation (FMT), and antibiotic strategies
- Therapeutic: FMT, probiotic, and lactoferrin
Enteral nutrition is a preemptive approach, and FMT can be proactive or reactive management. Lactoferrin, as the last part of the name (ferrin) implies, is an iron-binding protein that can help defend against bacteria and viruses to boost immunity, reduce inflammation, and promote gut health.
Dietary therapy in conjunction with immunosuppressive therapy is critical for the management of GVHD. Experts recommend nutritional support for patients with gut GVHD, with many organizations recommending EN as first-line therapy for allogeneic SCT patients. However, there is not uniform consensus on the positioning or timing of EN versus TPN. With a better understanding of the gut microbiome and the preemptive role of EN in modulating the gut environment for more healthy balance, oncology nurses can anticipate practice changes in the care of patients with gut GVHD.
ESPEN Guidelines on Nutrition in Cancer Patients
Challenging and Practical Aspects of Nutrition in Chronic Graft-versus-Host Disease
Enteral Versus Parenteral Nutrition as Nutritional Support After Allogeneic Hematopoietic Stem Cell Transplantation: a Systematic Review and Meta-Analysis
The Outcome and Complications of Total Parenteral Nutrition in Pediatric Hematopoietic Stem Cell Transplantation
Applications of Gut Microbiota in Patients With Hematopoietic Stem-Cell Transplantation
Insights Into the Role of Intestinal Microbiota in Hematopoietic Stem-Cell Transplantation