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SAN DIEGO — Patients receiving allogeneic hematopoietic cell transplantation (allo-HCT) for hematological conditions who adhere to high-fiber diets experience notable enhancements in overall survival rates and a diminished likelihood of encountering the severe complication of acute graft-versus-host disease (aGVHD), as demonstrated by recent findings.

Significantly, the results indicate that traditional low-fiber dietary guidelines for post-allo-HCT patients may oppose the associated benefits. 

“A marked reduction in fiber consumption during transplantation can be harmful. It represents a lost chance to foster a healthy gut microbiome, aid recovery from treatment-induced microbiota damage, and offer protection against GVHD,” stated lead researcher Jenny Paredes, PhD, a scientist affiliated with City of Hope National Medical Center in Duarte, California, in a press release for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

While the health advantages of dietary fiber on the gut microbiome are well-established, recent studies have indicated these benefits extend to outcomes following allo-HCT, with researchers observing enhanced overall survival linked to greater diversity in the gut microbiome, characterized by an increased prevalence of butyrate-producing bacteria and a decreased prevalence of enterococcus, Paredes elaborated during the presentation of the results.

Acute GvHD, a frequent and potentially fatal complication post-allo-HCT, can exhibit symptoms that resemble irritable bowel disease (IBD), such as abdominal pain or cramps, nausea, vomiting, and diarrhea. The recommendations for a low-fiber diet, which advocate for the exclusion of raw vegetables and fruits pre- and post-allo-HCT, aim to mitigate these symptoms and limit bacterial exposure.

However, given the emerging data suggesting that the benefits of dietary fiber might also play a role in the prevention of GvHD, Paredes and her team undertook further examination.

In this observational study, researchers analyzed dietary information from 173 allo-HCT patients at Memorial Sloan Kettering Cancer Center (MSKCC) over a timeframe extending from 10 days before transplantation to 30 days after, totaling 3837 patient-days.

Additional data collected included rRNA sequencing of fecal specimens and the concentration of fecal short-chain fatty acids. 

The study participants had a median age of 60, with 45% being female. The prevalent conditions treated included leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).

Upon grouping patients based on high- or low-fiber consumption, those in the high-fiber category exhibited significantly elevated rates of microbial α-diversity (P = .009), a higher prevalence of butyrate producers (P = .03), and increased butyrate concentration (P = .02), a short-chain fatty acid critical for gut health. 

Moreover, those in the high-fiber group demonstrated significantly improved overall survival rates in an analysis extending up to 24 months from day 12 of the study (P = .04).

When focusing on GvHD results, the authors examined data from 101 non-T-cell–depleted patients, identifying 29 patients without GvHD and 24 with lower gastrointestinal (GI) GvHD. 

Patients affected by lower GI GvHD showed significantly reduced fecal concentrations of butyrate (P = .03) and acetate (P = .02).

However, among those in the high-fiber intake group, there was a notably lower cumulative incidence of developing GvHD by day 100 (P = .034) and a reduced incidence of lower GI GvHD (P = .04).

A complementary preclinical study using a mouse model of GvHD illustrated that a fiber-rich diet (12% cellulose) significantly heightened the expression of genes linked with reduced GvHD, including IDO1 and CEACAM1, in addition to those associated with the enrichment of the bile acid pathway.

The results indicate a promising opportunity to enhance outcomes through relatively minor dietary adjustments, Paredes noted.

“Strategies to enhance the fiber content in these diets, alongside the safety these patients require, make this study particularly compelling,” she mentioned in a subsequent interview. 

“An increase in fiber intake by 10 to 20 grams per day has the potential to elevate microbiome diversity and the number of butyrate producers, both of which are correlated with higher overall survival rates after allo-HCT,” she explained.

“[For example], this could equate to consuming an avocado daily, or a small salad, or a small bowl of vegetable soup,” she continued. “I would advise organizations to reassess their menu planning and explore how to safely incorporate more fiber into meal options.”

Ultimately, “I believe the benefits of dietary interventions outweigh the risks associated with pharmacological ones,” Paredes added.

The duration necessary for a high-fiber diet to yield positive effects on allo-HCT outcomes would likely span the pre- and post-transplant phases, according to Paredes.

“With the survival analysis extending from 5 days prior to transplantation through to 12 days afterward, we are considering an intervention that may occur over approximately 20 days,” she mentioned.

“We want to capitalize on the pretransplantation period, particularly observing that increasing fiber consumption by around 20 grams during this time was shown to enhance overall survival after 24 months,” she added.

Nonetheless, Paredes cautioned that certain patients may not be ideal candidates for high-fiber dietary modifications. 

“Patients who have developed IBD-like symptoms or those experiencing severe GvHD, particularly those with lower GI-GvHD at grades 3 and 4, would not be suitable candidates for a high-fiber regimen,” she said. 

Could a High-Fiber Diet Decelerate MM Disease Progression?

The significant potential advantages of a high-fiber diet in blood-related conditions were further reinforced in a related study also conducted by MSKCC researchers and presented at the meeting, indicating promising indications that a fiber-rich plant-based diet may help to slow progression in multiple myeloma (MM).

NUTRIVENTION involved 20 patients with two precancerous conditions related to MM, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can persist for extended periods without evolving into MM, providing a potential window for preventive intervention against cancer progression.

Participants followed a controlled diet for 12 weeks alongside health coaching for an additional 3 months; there were no meals or coaching supplied during the remaining 1-year study duration. The participants had a median age of 62 and, given that being overweight/obesity poses a risk for MM, had a body mass index (BMI) of 25 kg/m² or higher.

The trial successfully achieved its endpoint regarding feasibility, boasting a 91% adherence rate in the initial 3 months. The intake of unprocessed plant foods surged from 20% at the outset to 92% during the intervention. Overall adherence was recorded at 58%. Insulin levels and anti-inflammatory markers also showed improvement, and despite no restrictions on caloric intake, a 7% sustainable reduction in BMI was noted. 

Significantly, two participants in the study demonstrated stabilization in disease progression.

“We observed enhancements across all dimensions, including metabolic health, microbiome diversity, and immune markers, and also recorded that two patients with progressive disease experienced a slowdown in progression during the intervention,” remarked principal investigator Urvi A. Shah, MD, in a press statement. 

“Even though it encompasses only two cases, to our knowledge, this has not previously been established in an intervention context where diet and lifestyle modifications can effectively slow or alter the course of the disease,” she emphasized.

The researchers warn that mouse study outcomes do not necessarily apply to human cases but refer to another mouse study with SMM, revealing that those fed a regular diet progressed to MM after a median of 12 weeks, whereas those on a high-fiber diet did so after a median of 30 weeks.

It is further notable that all mice in the normal-diet cohort transitioned to MM, while 40% of the mice on the high-fiber regimen did not. 

“Our findings indicate that a fiber-rich plant-based diet can enhance BMI, ameliorate insulin resistance, [and] enrich the microbiome through diversity and increased butyrate production. The resultant short-chain fatty acids can impact inflammation, immunity, and both innate and adaptive antitumor immunity, along with their effects on tumor or plasma cells,” Shah articulated during her presentation.

This research was backed by funding from the National Cancer Institute and private foundations. Paredes has disclosed no pertinent financial relationships. Shah has acknowledged relationships with Sanofi, Bristol Myers Squibb, and Janssen.