Higher fiber intake improves survival, reduces GVHD after HSCT
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Key takeaways:
- Greater fiber intake appeared linked to longer survival after allogeneic hematopoietic stem cell transplantation.
- Higher fiber intake also reduced risk for acute graft-versus-host disease in the lower gastrointestinal tract.
SAN DIEGO — Increased fiber intake after allogeneic hematopoietic stem cell transplantation appeared linked to improved outcomes, according to study results presented at ASH Annual Meeting and Exposition.
Transplant recipients who had higher fiber intake survived longer and appeared less likely to develop acute graft-versus-host disease in the lower gastrointestinal tract.
The findings suggest dietary fiber could be a potential strategy to prevent GVHD, Jenny Paredes, PhD, staff scientist at City of Hope, and colleagues concluded.
"We're not talking about a pharmacological intervention that could have potential secondary effects. We're talking about a noninvasive dietary intervention, which makes this very exciting," Paredes told Healio.
Background
Dietary fiber can affect the intestinal microbiome. It also can elevate production of bile acids and short-chain fatty acids, both of which are linked to intestinal homeostasis, according to study background.
Considerable literature supports the role of fiber intake for cancer prevention and reducing risk for cancer recurrence, Paredes said. NCI also has guidelines related to fiber consumption.
“We wanted to know whether fiber benefits patients who undergo transplant and to see if we could use fiber as a potential intervention to ameliorate the microbiome,” Paredes said. “These patients are unique in that fiber could be detrimental after transplantation due to the development of [inflammatory bowel disease-like] symptoms.”
Methods
Paredes and colleagues assessed the impact of dietary fiber on acute GVHD after allogeneic HSCT using a preclinical mouse model of GVHD with diet fiber concentrations, and by analyzing dietary patterns of allogeneic HSCT recipients.
Researchers hypothesized that a high-fiber diet may increase intestinal microbiome diversity and the concentration of beneficial microbial metabolites while reducing GVHD risk among transplant recipients.
Investigators obtained high-resolution dietary data from 173 allogeneic HSCT recipients at Memorial Sloan Kettering Cancer Center. The data spanned from 10 days before transplantation to 30 days after, equating to a combined 3,837 patient days.
They also obtained 16S ribosomal RNA sequencing data from fecal samples, as well as gas chromatography-mass spectrometry data of fecal short-chain fatty acids concentration to establish subgroups of those who did or did not develop acute GHVD of the lower GI tract.
Paredes and colleagues assessed the associations between fiber intake and microbial markers such as alpha-diversity, butyrate producers, and concentrations of fecal short-chain fatty acids between those who developed lower GI tract acute GVHD and those who did not.
They performed latent trajectory class analysis to identify patients’ dietary intake patterns, as well as to correlate fiber intake and survival, in an attempt to account for considerable variation in patients’ dietary intake trajectories and macronutrients interactions.
Investigators also assessed how dietary fiber affects GVHD by using a preclinical mouse GVHD model treated with cellulose at four concentrations — 0%, 6%, and 12%. They also evaluated survival, fecal microbial composition, short-chain fatty acid concentration, immune composition and single cell gene expression from the lamina propria of mouse colons.
Key findings
The analysis of allogeneic HSCT recipients showed a statistically significant association between higher fiber intake and microbial alpha-diversity (P = .009), greater abundance of butyrate producers (P = .03) and higher concentration of butyrate (P = .02).
Analyses adjusted for fiber intake showed HSCT recipients who developed GVHD in the lower GI tract had significantly reduced fecal concentrations of acetate (P = .02) and butyrate (P = .03).
“When we were able to validate that increasing fiber intake and increasing butyrate producers, lead to lower acute GVHD, that was pleasantly surprising,” Paredes said. “We hypothesized it, but to have the complete picture and have all the dynamics come into play was very gratifying.”
The latent trajectory class analysis revealed those with high fiber intake achieved significantly longer OS (log-rank P = .04) and had lower cumulative incidence of acute GVHD in the lower GI tract (Gray’s P = .04).
Researchers hoped to evaluate survival over 5 years; however, they were only able to follow a small subset of patients for that long. Their OS analysis spanned 24 months, with results showing about a 10 percentage-point difference in survival with high fiber intake vs. low fiber intake.
“We need to have longer follow-up to make more definitive conclusions beyond 24 months,” Paredes said. “However, given we’re talking about survival in a cohort of 173 patients, I do think the survival data we saw at 24 months is clinically meaningful.”
Results from the preclinical GVHD model showed mice that received a fiber-rich diet — defined as 12% cellulose — exhibited a significant reduction in GVHD lethality (P = .02), greater microbial alpha-diversity (P = .02), reduced relative abundance of Enterococcus faecalis (P = .001 vs. 0%), a higher ratio of regulatory T cells vs. conventional T cells, and a greater concentration of cecal butyrate (P = .03 vs. 0%; P = .03 vs. 6%).
Single cell sequencing analysis of CD4-positive T cells of mice given the 12% cellulose diet exhibited significantly greater expression of genes associated with reduced GVHD, such as indoleamine 2,3-dioxygenase 1 (IDO1) and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1); as well as genes associated with epithelial homeostasis and lower T cells’ mediated inflammation.
Next steps
The decision about whether to encourage stem cell transplant recipients to adhere to a high-fiber diet must be evaluated on a case-by-case basis, Paredes said.
“The decision to limit fiber intake from raw foods and fruits that can’t be peeled is because these patients require a low microbiome-exposure diet to due to risks of infection,” she said. “Acknowledging that, though, I think it is possible to tailor meal plans a little better, accounting for alternative fiber sources that could be cooked and made safe for these patients. I hope our study encourages clinicians and institutions to re-evaluate the meal planning they currently have and include more fiber.”
The research team evaluated more than 35,000 meals, followed patients daily and collected more than 1,000 stool samples as part of their analysis, Paredes said.
“We were extremely careful and detail-oriented because our approach was just as thorough as a pharmacological intervention,” she said. “In addition to our findings, I hope this study delivers the message that food is also a therapy, and nutritional studies should be taken to this level of detail.”
Perspective
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Mikkael A. Sekeres, MD
This is another study that looks at whether the microbiome can have an impact on patients undergoing one of our most aggressive procedures — bone marrow transplant.
Should patients with blood or bone marrow cancers uniformly adopt a high-fiber diet?
My cautionary note is that a lot of the data actually are preclinical. There is a lot of substantiating data in mouse models, and boy is it provocative that if we modify someone's diet, we'll modify the microbiome and those folks undergoing treatment for cancer will have a better outcome.
The important thing to remember is we need to wait for clinical trials that are prospectively conducted before we whole-hog recommend patients with hematologic malignancies undergo more restrictive diets.
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Paredes J, et a. Abstract 259. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
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