GRAPE SEED FLOUR SUPPLEMENTATION IN PATIENTS WITH CACHEXIA ASSOCIATED WITH COLORECTAL CANCER WITHOUT PRIOR CANCER TREATMENT AND ITS IMPACT ON GUT MICROBIOTA MODULATION

Abstract

Objective: To evaluate the effect of grape seed flour supplementation versus corn starch placebo on the gut microbiota of patients with cachexia associated with colorectal cancer.

Methods: A phase 2, randomized, triple-masked, placebo-controlled clinical trial with 20 patients (n=9 intervention, n=11 placebo). Participants received capsules containing 8g/day of grape seed flour or placebo for 28 days. Secondary objectives included assessment of plasma and serum inflammatory markers, dietary intake, and gut microbiota profile. Fecal samples were collected before and after the intervention and analyzed by next-generation sequencing (NGS) using QIIME 2 and DADA2. Blood samples were collected for analysis of inflammatory markers, and dietary intake was recorded by 24-hour recall.

Results: Supplementation did not significantly alter alpha diversity indices (Chao1, Simpson, Shannon). A significant increase in Proteobacteria and a reduction in Bacteroidota were observed in supplemented patients. The increase in BMI correlated positively with Blautia and negatively with Bacteroidota. Reactance showed a positive correlation with Bacteroidota.

Conclusion: Supplementation with grape seed flour for 28 days did not significantly modify the overall profile of the intestinal microbiota in patients with cachexia associated with colorectal cancer, showing effects similar to placebo. However, there was a positive impact on secondary variables, including inflammatory markers, suggesting a potential benefit in metabolic and immunological parameters. Despite the limitations of the study, the results provide relevant contributions to the understanding of cancer cachexia, especially regarding the use of products rich in polyphenols and dietary fiber as therapeutic adjuvants.