“Francesca Castro, R.D., from the Memorial Sloan Kettering Cancer Center in New York City, and colleagues conducted a single-arm pilot trial implementing an HFPBD intervention for 12 weeks and behavioral counseling for 24 weeks in 20 patients with a body mass index (BMI) ≥25 kg/m2 and MGUS/SMM.
The researchers found that the HFPBD was safe and feasible and yielded improvement in diet quality and microbiome. From baseline to week 12, there was an increase in median dietary adherence from 20 to 91 percent, while median BMI decreased (−6.6 percent). Median dietary fiber increased from 12.3 to 24 g/1,000 kcal/day from baseline to week 12, and the median Healthy Eating Index (HEI)-2020 score increased from 61.4 to 80.
From baseline to week 12, an increase was seen in median fecal microbiome α-diversity by 16S ribosomal RNA gene sequencing (6.18 to 8.42) and in relative abundance of butyrate producers (RABP; median, 0.03 to 0.08).
There was a negative correlation observed for α-diversity with BMI and a positive correlation with fiber, HEI-2020 score, and dietary adherence. Positive correlations were seen for fiber intake, HEI-2020 scores, and dietary adherence with higher RABP. At weeks 24 and 52, the findings were consistent.
“Our results highlight the importance of improved dietary quality in early disease states and could provide guidance for future clinical trials,” Castro said in a statement.”
A High-Fiber Dietary Intervention (NUTRIVENTION) in Precursor Plasma Cell Disorders Improves Biomarkers of Disease and May Delay Progression to Myeloma
The HFPBD intervention was safe, feasible, improved quality of life and addressed modifiable risk factors – metabolic profile (improved BMI, insulin resistance, adiponectin leptin ratio), microbiome profile (increased alpha-diversity and butyrate producers) and immune (decreased inflammation and increased anti-inflammatory classical monocyte) subsets. A reduction in long-term progression trajectory was observed in 2 patients.
Consistently, the high fiber diet delayed progression from mSMM to mMM in Vk*MYC mice increasing median progression-free survival from 12 weeks in the control arm to 30 weeks in the high fiber diet intervention arm.
Additionally, in the intervention arm 40% of mice did not progress to mMM during the study period whereas all mice in the control arm progressed. Both human and mouse data showed that HFPBD modulated gut microbiota composition favoring the expansion of butyrate-producing bacteria. Additionally, short-chain fatty acids were increased in the feces of mice fed a high fiber diet.
Integrated analysis from human bone marrow and peripheral blood analysis indicated that the dietary intervention reduced inflammatory biomarkers and skewed the immune response towards T helper and CD14+ monocytes. Consistently, the bone marrow of Vk*MYC mice fed high fiber diet was more infiltrated by IFNg-producing T lymphocytes while displaying less exhausted T cells and immunosuppressive myeloid cells.
Conclusion
This is the first interventional clinical trial and in vivo study to show that a HFPBD intervention may delay progression from MGUS/SMM to MM. To our knowledge there has been no similar dietary interventional study in hematological cancers or solid tumors. Together our in vivo and clinical data support the beneficial anti-inflammatory role of a HFPBD providing a link between diet, microbiota, and immune modulation to delay disease progression in MGUS/SMM.