Recent advances that allow us to collect more data on DNA sequences and metabolites have increased our understanding of connections between the intestinal microbiota and metabolites, at a whole-systems level. We can also now better study the effects of specific microbes on specific metabolites. Here, we review how the microbiota determines levels of specific metabolites, how the metabolite profile develops in infants, and prospects for assessing a person’s physiological state based on their microbes and/or metabolites. Although data acquisition technologies have improved, computational challenges to integrating data from multiple levels remain formidable; developments in this area will significantly improve our ability to interpret current and future datasets.

BackgroundObesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene), a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established.MethodsWe investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity) and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis.ResultsResveratrol (100-150 μM) exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway.ConclusionsFor the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and activation of p53, suggesting its potential role as a chemotherapeutic agent.

Limited information is available regarding the metabolic consequences of intestinal dysbiosis in dogs with acute onset of diarrhea. The aim of this study was to evaluate the fecal microbiome, fecal concentrations of short-chain fatty acids (SCFAs), as well as serum and urine metabolites in healthy dogs (n=13) and dogs with acute diarrhea (n=13). The fecal microbiome, SCFAs, and serum/urine metabolite profiles were characterized by 454-pyrosequencing of the 16S rRNA genes, GC/MS, and untargeted and targeted metabolomics approach using UPLC/MS and HPLC/MS, respectively. Significantly lower bacterial diversity was observed in dogs with acute diarrhea in regards to species richness, chao1, and Shannon index (p=0.0218, 0.0176, and 0.0033; respectively). Dogs with acute diarrhea had significantly different microbial communities compared to healthy dogs (unweighted Unifrac distances, ANOSIM p=0.0040). While Bacteroidetes, Faecalibacterium, and an unclassified genus within Ruminococcaceae were underrepresented, the genus Clostridium was overrepresented in dogs with acute diarrhea. Concentrations of fecal propionic acid were significantly decreased in acute diarrhea (p=0.0033), and were correlated to a decrease in Faecalibacterium (ρ=0.6725, p=0.0332). The predicted functional gene content of the microbiome (PICRUSt) revealed overrepresentations of genes for transposase enzymes as well as methyl accepting chemotaxis proteins in acute diarrhea. Serum concentrations of kynurenic acid and urine concentrations of 2-methyl-1H-indole and 5-Methoxy-1H-indole-3-carbaldehyde were significantly decreased in acute diarrhea (p=0.0048, 0.0185, and 0.0330, respectively). These results demonstrate that the fecal dysbiosis present in acute diarrhea is associated with altered systemic metabolic states.

Polyphenols from fruits and vegetables exhibit anticancer properties both in vitro and in vivo and specialty potatoes are an excellent source of dietary polyphenols, including phenolic acids and anthocyanins. This study investigated the effects of specialty potato phenolics and their fractions on LNCaP (androgen dependent) and PC-3 (androgen independent) prostate cancer cells. Phenolic extracts from four specialty potato cultivars CO112F2-2, PATX99P32-2, ATTX98462-3 and ATTX98491-3 and organic acid, phenolic acid and anthocyanin fractions (AF) were used in this study. CO112F2-2 cultivar extracts and their AF at 5 mug chlorogenic acid eq/ml were more active and inhibited cell proliferation and increased the cyclin-dependent kinase inhibitor p27 levels in both LNCaP and PC-3 cells. Potato extract and AF induced apoptosis in both the cells and, however, the effects were cell context dependent. Cell death pathways induced by potato extract and AF were associated with mitogen-activated protein kinase and c-jun N-terminal kinase activation and these kinases activated caspase-independent apoptosis through nuclear translocation of endonuclease G (Endo G) and apoptosis-inducing factor in both cell lines. Induction of caspase-dependent apoptosis was also kinase dependent but was observed only in LNCaP cells. Kinase inhibitors reversed this nuclear translocation of endonuclease G and apoptosis-inducing factor. This is the first report showing that the cytotoxic activities of potato extract/AF in cancer cells were due to activation of caspase-independent apoptosis. Current studies are focused on identifying individual components of the AF responsible for the induction of cell death pathways in prostate and other cancer cell lines and developing potato cultivars that overexpress these active compounds.

The influence of genotype, cooking method, and storage treatments on potato compounds associated with improved human health was analyzed. Antioxidant activity (AA), total phenolics (TP), and total carotenoids (xanthophyll carotenoids, CAR) were determined in eight genotypes using 2,2-diphenyl-1-picrylhydrazyl (DPPH), Folin-Ciocalteu reagent, and spectrophotometric absorbance, respectively. Individual phenolic and carotenoid composition was analyzed using high performance liquid chromatography (HPLC) in three genotypes of potato. Samples were subjected to a combination of storage conditions for approximately 4 months (non-stored or stored for 110 days at either 4°C, 4°C with an additional 10 days of reconditioning at 20°C, or 20°C storage) and cooking methods (baking, boiling, frying, or microwaving); an uncooked sample was used as a control. The non-stored samples had lower amounts of CAR, AA, and TP along with the individual compounds compared to the various storage regimes, while the recondition storage treatment produced equal or higher levels of TP and individual phenolics than any other storage regime. No cooking and boiling resulted in significantly lower AA and TP, as compared to baking, frying and/or microwaving. Baking, frying and/or microwaving also increased the levels of chlorogenic acid, caffeic acid, (-) epicatechin, p-coumaric acid and vanillic acid, but decreased quercetin dihydrate when compared to uncooked samples. Most health promoting compounds were enhanced by one or both postharvest processing parameters (storage and cooking); however, t-cinnamic acid, and lutein were not affected.Resumen Se analizó la influencia del genotipo, del método de cocinado y de tratamientos en el almacén, sobre los compuestos de papa asociados con el mejoramiento de la salud humana. Se determinó la actividad antioxidante (AA), fenoles totales (TP), y carotenoides totales (carotenoides xantofílicos, CAR), en ocho genotipos, usando 2,2-difenil-1-picrilhidrazilo (DPPH), el reactivo de Folin-Ciocalteau, y la absorbancia espectrofotométrica, respectivamente. Se analizaron los fenoles individuales y la composición de los carotenoides usando cromatografía de líquidos de alta resolución (HPLC) en tres genotipos de papa. Las muestras estuvieron sujetas a una combinación de condiciones de almacenamiento por aproximadamente cuatro meses (sin almacenar, o almacenadas por 110 días ya fuera a 4°C, a 4°C con diez días adicionales de reacondicionamiento a 20°C, o a 20°C en el almacén), y métodos de cocinado (horneadas, hervidas, fritas, o en el horno de microondas); se usó una muestra sin cocinar como testigo. Las muestras sin almacenar tuvieron las cantidades más bajas de CAR, AA, y TP, junto con los compuestos individuales comparados a los diversos regímenes de almacenamiento, mientras que el tratamiento de reacondicionamiento en el almacén produjo niveles iguales o mayores de TP y de fenoles individuales que cualquier otro régimen de almacenamiento. Sin cocinar y hervidas resultaron en contenido más bajo de AA y TP, comparadas ...