Grape seed proanthocyanidin extract (GSPE) modulates several parameters involved in metabolic syndrome. GSPE is a mixture of compounds, some which are rapidly absorbed, while others remain in the lumen where they might have effects that are translated to the whole organism. Our aim was to decipher if the 8-day treatment of GSPE, previously shown to reduce food intake, induces changes in the microbiota and enterohormone secretion. The ratio of Firmicutes : Bacteroidetes was lower in the microbiota of GSPE-treated rats compared to controls, and differences in several taxonomic families and genera were observed. Such modulation led to a reduction in cecal butyrate content. GSPE also increased plasma glucagon-like-peptide-1 (GLP-1). Gallic acid did not induce major changes in the microbiota profile nor in GLP-1 secretion. Correlations between several microbiota taxa and plasma triacylglycerol, adiposity, and enterohormones were observed. Modulation of microbiota may be one of the mechanism by which GSPE impacts metabolic health.

GSPE at a dose of 0.5 g/kg can reduce body weight by limiting food intake and activating energy expenditure in subcutaneous adipose tissue.

Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occur in a limited subset of tumor cells that localize in defined niches. The rest of the tumor cells undergo an irreversible loss of their biosynthetic capacities as a consequence of differentiation. Cancer cells within the biosynthetic domains are characterized by elevated levels of the RNA Polymerase 1 subunit A -POLR1A. Genetic ablation of POLR1A-high cell population imposes an irreversible growth arrest to CRCs. We show that elevated biosynthesis defines stemness in both LGR5+ and LGR5-tumor cells. Therefore, a common architecture in CRC is a simple cell hierarchy based on the differential capacity to transcribe ribosomal DNA and synthesize proteins.

Grape-seed proanthocyanidins' role as stimulators of active GLP-1 in rats suggests that they could be effective as satiating agents. Wistar rats were used to study the effects of proanthocyanidins on food intake with different doses, administration times and proanthocyanidin extract compositions. A dose of 423 mg of phenolics per kg body weight (BW) of grape-seed proanthocyanidin extract (GSPE) was necessary to decrease the 12-hour cumulative food intake by 18.7 ± 3.4%. Proanthocyanidins were effective when delivered directly into the gastrointestinal tract one hour before, or simultaneously at the start of the feeding period. Proanthocyanidins without galloyl forms, such as those from cocoa extract, were not as effective as grape-seed derived forms. GSPE increased the portal levels of active GLP-1 and total ghrelin and decreased the CCK levels, simultaneously with a decrease in gastric emptying. In conclusion, grape-seed proanthocyanidins could be useful as a satiating agent under the conditions defined in this study.