High-fiber diet is associated with improved outcomes in stem cell transplantation, GvHD

SAN DIEGO — Recipients of allogeneic hematopoietic cell transplantation (allo-HCT) for blood disorders maintain a diet high in fiber, significantly improving overall survival and potentially life-threatening acute graft versus The risk of developing host disease complications (aGVHD) has been shown to be reduced, a new study shows.

Importantly, the findings suggest that standard recommendations for patients on a low-fiber diet after allogeneic HCT may be counter to its potential benefits.

“Significant reductions in fiber intake during transplantation are detrimental; the opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota damage, and protect against GVHD is lost,” said the first author. said Dr. Jenny Paredes, city staff scientist. Hope National Medical Center in Duarte, California, said in a press statement about the study published here. American Society of Hematology (ASH) 2024 Annual Meeting.

The health benefits of dietary fiber on the gut microbiome are well-documented, and their effects have recently been shown to extend to outcomes following allogeneic HCT in general. researcher Presenting the results of the study, Professor Paredes said that increased diversity of the gut microbiota increases overall survival, including increased abundance of butyrate-producing substances and decreased abundance of enterococci. He explained that he had discovered.

Acute GvHD is a common and potentially life-threatening complication of allogeneic HCT that can present with symptoms similar to irritable bowel disease (IBD), including abdominal pain and cramps, nausea, vomiting, and abdominal pain. there is. diarrhea. Low-fiber dietary recommendations, such as avoiding raw vegetables and fruits before and after an allo-HCT procedure, are designed to not only reduce exposure to bacteria but also counteract their effects.

But data suggesting the potential benefits of dietary fiber may extend to preventing GvHD led Paredes and colleagues to investigate further.

This observational study evaluated all dietary data for 173 allogeneic HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days before transplant to 30 days after transplant (3837 patient days total).

Data collected from patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentrations.

The median age of participants was 60 years, and 45% were female. The most common disease treated was leukemia (50%). myelodysplastic syndrome (25%), and non-hodgkin lymphoma (8.7%).

When we stratified patients based on whether they had high or low dietary fiber intake, we found that patients with high dietary fiber intake had significantly higher rates of microbial alpha diversity (P = .009), more abundant butyrate products (P = .03), higher concentrations of butyrate (P = .02), short-chain fatty acids that play an important role in gut health.

Furthermore, in the 24-month analysis, overall survival was significantly higher in the high-fiber group compared to study day 12 (P = .04).

Focusing on GvHD outcomes, the authors further evaluated data from 101 patients without T-cell depletion and identified 29 patients without GvHD and 24 patients who developed lower gastrointestinal (GI) GvHD. did.

Patients with low gastrointestinal GvHD had significantly lower fecal butyrate concentrations (P = .03) and acetate (P = .02).

However, patients in the high fiber group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034), lower incidence of low GI GvHD (P = .04).

Another preclinical analysis of a GvHD mouse model further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of the following genes associated with reduced GvHD. IDO1 and CEACAM1associated with enhancement of the bile acid pathway.

The findings suggest that relatively small dietary changes may improve outcomes, Paredes said.

“These strategies to increase fiber levels in the diet, combined with the safety needs of patients, are what makes this study interesting,” she said in an interview.

“Increasing fiber intake by 10-20 grams per day can increase microbiome diversity and the amount of butyrate products, which correlates with increased overall survival after allogeneic HCT. ” she continued.

”[For instance]”That could be one avocado per day, a small salad per day, a small vegetable soup per day,” she added. Incorporate it into your diet in a safe way. ”

Ultimately, “I think dietary intervention outweighs the risks of pharmacological intervention,” Paredes added.

Paredes added that the period of high-fiber diet required to produce a beneficial effect on allogeneic HCT outcomes likely spans the pre- and post-transplant periods.

“Survival analysis is done from five days before transplant to 12 days after transplant, so we think the intervention could be as long as 20 days,” she said.

“We especially want to take advantage of the pre-transplant period. We're seeing that increasing fiber intake by just about 20 grams during this period has been shown to improve overall survival after 24 months. ” Paredes added.

Importantly, however, Paredes cautioned that high-fiber dietary changes may not be appropriate for some patients.

“For example, patients who develop IBD-like symptoms, those with severe GvHD, or those with low levels of GI-GvHD grade 3 or 4 may not be good candidates for a high-fiber diet,” she said. Ta.

Does a high-fiber diet slow the progression of MM disease?

The potentially important benefits of high-fiber diets in blood diseases were further demonstrated in the following papers: another study MSKCC researchers presenting at the conference also showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression. multiple myeloma (MM).

The nutritional study included 20 patients with two precancerous MM conditions. Monoclonal gammaglobulinopathy of unknown significance Smoldering multiple myeloma (MGUS) and smoldering multiple myeloma (SMM) can persist for years without progression to MM, presenting potential opportunities for intervention to prevent progression to cancer. Researchers speculate that it may be possible.

Patients were provided with 12 weeks of dietary management and an additional three months of health coaching. No meals or instruction were provided during the remaining year of study. The median age of participants was 62 years and they were overweight/obesity A risk factor for MM, body mass index (BMI) was 25 kg/m3² That's all.

The trial achieved a 91% compliance rate in the first 3 months and met the feasibility endpoint. Intake of unprocessed plant foods increased from 20% at baseline to 92% after the intervention. Overall compliance was 58%. insulin Anti-inflammatory markers also improved, with a sustained 7% reduction in BMI despite no caloric restriction.

Of note, disease progression stabilized in two patients in the study.

“We saw improvements in all areas, including metabolic, microbiome, and immune system markers,” said lead researcher Uruvi A. Shah, MD, who said, “We saw improvements in all areas, including metabolic, microbiome, and immune system markers. Additionally, two patients with advanced disease slowed progression with the intervention. We also confirmed that it stabilized and decelerated.” In a press statement.

“To our knowledge, in only two cases, no intervention setting has ever shown that diet or lifestyle changes can actually slow or change the trajectory of the disease.” she pointed out.

Although the researchers caution that findings in mice do not necessarily translate to humans, other experiments using mice with SMM showed that animals fed a normal diet developed MM after a median of 12 weeks. We note that animals fed a normal diet showed progression to MM in a median of 30 weeks. High fiber diet.

Of note, all mice in the normal diet group progressed to MM, whereas 40% of mice in the high fiber group did not.

“A plant-based diet rich in fiber improves BMI and insulin resistance [and] “The microbiome, through its diversity and production of butyrate products and short-chain fatty acids, can influence inflammation, immunity, innate and adaptive anti-tumor immunity, tumor cells or plasma cells,” Shah said during his presentation. stated.

This research was supported by funding from the National Cancer Institute and private foundations. Paredes reports no relevant financial relationships. Shah reports on relationships with Sanofi and Bristol-Myers Squibb, And Janssen.