This study shows, for the first time to our knowledge, that consumption of cocoa flavanols can significantly affect the growth of select gut microflora in humans, which suggests the potential prebiotic benefits associated with the dietary inclusion of flavanol-rich foods. This trial was registered at clinicaltrials.gov as NCT01091922.

We have investigated the bacterial-dependent metabolism of (2 )-epicatechin and (þ )-catechin using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal region of the human large intestine. Incubation of (2)-epicatechin or (þ )-catechin (150 mg/l or 1000 mg/l) with faecal bacteria, led to the generation of 5-(3 0 ,4 0 -dihydroxyphenyl)-g-valerolactone, 5-phenyl-g-valerolactone and phenylpropionic acid. However, the formation of these metabolites from (þ )-catechin required its initial conversion to (þ )-epicatechin. The metabolism of both flavanols occurred in the presence of favourable carbon sources, notably sucrose and the prebiotic fructo-oligosaccharides, indicating that bacterial utilisation of flavanols also occurs when preferential energy sources are available. (þ )-Catechin incubation affected the growth of select microflora, resulting in a statistically significant increase in the growth of the Clostridium coccoides -Eubacterium rectale group, Bifidobacterium spp. and Escherichia coli, as well as a significant inhibitory effect on the growth of the C. histolyticum group. In contrast, the effect of (2)-epicatechin was less profound, only significantly increasing the growth of the C. coccoides -Eubacterium rectale group. These potential prebiotic effects for both (þ )-catechin and (2 )-epicatechin were most notable at the lower concentration of 150 mg/l. As both (2)-epicatechin and (þ )-catechin were converted to the same metabolites, the more dramatic change in the growth of distinct microfloral populations produced by (þ )-catechin incubation may be linked to the bacterial conversion of (þ )-catechin to (þ)-epicatechin. Together these data suggest that the consumption of flavanol-rich foods may support gut health through their ability to exert prebiotic actions. Flavanols: Prebiotics: Faecal microflora: Large intestineRepresenting one of the most important lifestyle factors, diet can strongly influence the incidence and onset of CVD (1) , and thus a healthy diet is an essential factor for healthy ageing (2) . A number of dietary intervention studies in human subjects and animals, in particular those using Vitis vinifera (grape), Camellia sinensis (tea) and Theobroma cacao (cocoa) have demonstrated beneficial effects on vascular function (3 -5) . While such foods and beverages differ greatly in chemical composition and macro-and micronutrient content, they have in common that they are amongst the major dietary sources of flavanols. The in vivo effects of flavanols will be dependent on the absorption and metabolism of flavanols in the gastrointestinal tract. Studies have indicated that flavanols are subject to extensive metabolism by phase I and II enzymes to yield O-methylated, sulfated and glucuronidated forms during transfer from the small-intestinal lumen to the portal blood (6) . However, significant amounts of ingested (2 )-epicatechin, (þ)-catechin, and their structurally related oligomeric forms (procyanidins), escape absorption in the small intestine, instead rea...

We have conducted a detailed investigation into the absorption, metabolism and microflora-dependent transformation of hydroxytyrosol (HT), tyrosol (TYR) and their conjugated forms, such as oleuropein (OL). Conjugated forms underwent rapid hydrolysis under gastric conditions, resulting in significant increases in the amount of free HT and TYR entering the small intestine. Both HT and TYR transferred across human Caco-2 cell monolayers and rat segments of jejunum and ileum and were subject to classic phase I/II biotransformation. The major metabolites identified were an O-methylated derivative of HT, glucuronides of HT and TYR and a novel glutathionylated conjugate of HT. In contrast, there was no absorption of OL in either model. However, OL was rapidly degraded by the colonic microflora resulting in the formation of HT. Our study provides additional information regarding the breakdown of complex olive oil polyphenols in the GI tract, in particular the stomach and the large intestine.

Coffee is a relatively rich source of chlorogenic acids (CGA), which, as other polyphenols, have been postulated to exert preventive effects against CVD and type 2 diabetes. As a considerable proportion of ingested CGA reaches the large intestine, CGA may be capable of exerting beneficial effects in the large gut. Here, we utilise a stirred, anaerobic, pH-controlled, batch culture fermentation model of the distal region of the colon in order to investigate the impact of coffee and CGA on the growth of the human faecal microbiota. Incubation of coffee samples with the human faecal microbiota led to the rapid metabolism of CGA (4 h) and the production of dihydrocaffeic acid and dihydroferulic acid, while caffeine remained unmetabolised. The coffee with the highest levels of CGA (P, 0·05, relative to the other coffees) induced a significant increase in the growth of Bifidobacterium spp. relative to the control vessel at 10 h after exposure (P, 0·05). Similarly, an equivalent quantity of CGA (80·8 mg, matched with that in high-CGA coffee) induced a significant increase in the growth of Bifidobacterium spp. (P, 0·05). CGA alone also induced a significant increase in the growth of the Clostridium coccoides -Eubacterium rectale group (P,0·05). This selective metabolism and subsequent amplification of specific bacterial populations could be beneficial to host health.

Meta-analyses of randomized controlled trials (RTC) have confirmed the hypocholesterolaemic effect of oats and oat based fibers. However, the mechanisms by which oats or oat fractions lower cholesterol is not totally clear. Recognizing the important role of the gut microbiome in metabolism and metabolic disease risk, we examined the impact of whole grain oat Granola (WGO) on the human gut microbiota and cardio-metabolic risk factors using a randomized crossover dietary intervention in at risk individuals (ClinicalTrials.gov Identifier: NCT01925365). We randomized 32 individuals at risk of developing cardio-metabolic disease by virtue of mild hypercholesterolaemia or glucose intolerance, into two groups consuming either 45 g of WGO or non-whole grain (NWG) breakfast cereals daily for two 6-week intervention periods separated by a 4-week wash out period in a randomized, controlled, crossover, double-blinded design. Confirming the cholesterol lowering effect of WGO, we observed a significant time by treatment interaction, for total cholesterol (TC) (P = 0.0001) and LDL-cholesterol (LDL-C) (P = 0.02) compared to NWG. A significant time by treatment interaction was also observed for the relative abundance of fecal bifidobacteria (P = 0.0001), lactobacilli (P = 0.001) and total bacterial count (P = 0.008), which were all elevated after consumption of WGO. Daily consumption of WGO resulted in a prebiotic effect on the human gut microbiota composition and significant reductions in TC and LDL-C concentrations. Prebiotic modulation of the human gut microbiota may thus constitute a previously unrecognized mechanism contributing to the hypocholesterolaemic effects of whole grain oat Granola.