Background: Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon, but human data supporting this suggestion are weak. Objective: The objective was to verify whether the prebiotic concept (selective interaction with colonic flora of nondigested carbohydrates) as induced by a synbiotic preparation—oligofructose-enriched inulin (SYN1) + Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (BB12)—is able to reduce the risk of colon cancer in humans. Design: The 12-wk randomized, double-blind, placebo-controlled trial of a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12 was conducted in 37 colon cancer patients and 43 polypectomized patients. Fecal and blood samples were obtained before, during, and after the intervention, and colorectal biopsy samples were obtained before and after the intervention. The effect of synbiotic consumption on a battery of intermediate bio-markers for colon cancer was examined. Results: Synbiotic intervention resulted in significant changes in fecal flora: Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased. The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients. Genotoxicity assays of colonic biopsy samples indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period. Synbiotic consumption prevented an increased secretion of interleukin 2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon γ in the cancer patients. Conclusions: Several colorectal cancer biomarkers can be altered favorably by synbiotic intervention.

Astaxanthin (AX), a lipid-soluble pigment belonging to the xanthophyll carotenoids family, has recently garnered significant attention due to its unique physical properties, biochemical attributes, and physiological effects. Originally recognized primarily for its role in imparting the characteristic red-pink color to various organisms, AX is currently experiencing a surge in interest and research. The growing body of literature in this field predominantly focuses on AXs distinctive bioactivities and properties. However, the potential of algae-derived AX as a solution to various global environmental and societal challenges that threaten life on our planet has not received extensive attention. Furthermore, the historical context and the role of AX in nature, as well as its significance in diverse cultures and traditional health practices, have not been comprehensively explored in previous works. This review article embarks on a comprehensive journey through the history leading up to the present, offering insights into the discovery of AX, its chemical and physical attributes, distribution in organisms, and biosynthesis. Additionally, it delves into the intricate realm of health benefits, biofunctional characteristics, and the current market status of AX. By encompassing these multifaceted aspects, this review aims to provide readers with a more profound understanding and a robust foundation for future scientific endeavors directed at addressing societal needs for sustainable nutritional and medicinal solutions. An updated summary of AXs health benefits, its present market status, and potential future applications are also included for a well-rounded perspective.

Cyclooxygenase enzymes (COX-1 and COX-2) catalyse the production of prostaglandins from arachidonic acid. Prostaglandins are important mediators in the inflammatory process and their production can be reduced by COX-inhibitors. Endocannabinoids, endogenous analogues of the plant derived cannabinoids, occur normally in the human body. The Endocannabinoids are structurally similar to arachidonic acid and have been suggested to interfere with the inflammatory process. They have also been shown to inhibit cancer cell proliferation. Anti-inflammatory effects of cannabinoids and endocannabinoids have been observed, however the mode of action is not yet clarified. Anti-inflammatory activity (i.e., inhibition of COX-2) is proposed to play an important role in the development of colon cancer, which makes this subject interesting to study further. In the present work, the six cannabinoids tetrahydrocannabinol (Δ9-THC), tetrahydrocannabinolic acid (Δ9-THC-A), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG) and cannabigerolic acid (CBGA), isolated from Cannabis sativa, were evaluated for their effects on prostaglandin production. For this purpose an in vitro enzyme based COX-1/COX-2 inhibition assay and a cell based prostaglandin production radioimmunoassay were used. Cannabinoids inhibited cyclooxygenase enzyme activity with IC50 values ranging from 1.7·10−3 to 2.0·10−4 M.

The inducible enzyme cyclooxygenase-2 (COX-2) plays a major role in the regulation of inflammation and possibly in the development of colon cancer. The aim of the present study was to screen for COX-2 inhibitors in samples of fecal water (the aqueous phase of feces) and investigate whether phenolic compounds are responsible for any observed effects on COX-2. Volunteers (n = 20) were recruited and asked to supply a 24-h stool sample. Fecal water samples were prepared and analyzed by GC-MS for their content of phenolic compounds. These samples were also evaluated for their effects on COX-2 protein levels (Western blot) and prostaglandin (PG)E₂ production in tumor necrosis-α–stimulated HT-29 cells and pure enzymatic activity in a COX-2–catalyzed prostaglandin biosynthesis in vitro assay. The major phenolic compounds identified were phenylpropionic acid, phenylacetic acid, cinnamic acid, and benzoic acid derivatives. Of 13 fecal water samples analyzed, 12 significantly decreased PGE₂ production (range 5.4–39.7% inhibition, P-value < 0.05) compared with control cells and 13 of 14 samples analyzed decreased COX-2 protein levels in HT-29 cells (19–63% inhibition). Of the 20 fecal water samples, 2 also weakly inhibited enzymatic activity of purified COX-2 (22–24% inhibition). Three compounds identified in fecal water, 3-phenylpropionic acid, 3-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)-propionic acid, decreased the protein level at 250 μmol/L (15–62% inhibition). This study shows for the first time that human fecal water contains components that can affect both the COX-2 protein level and enzymatic activity.

Many phytochemicals found in the diet may prevent colon carcinogenesis by affecting biochemical processes in the colonic mucosa. Inflammation and subsequent elevation of the enzyme cyclooxygenase-2 (COX-2) are two such factors involved in the development of colon cancer, and inhibition of these processes could be important targets for chemoprevention. We have previously shown COX-2 inhibitory activity locally in the colon; e.g. in human fecal water from a group of vegetarians. In this study we focus on 2-pentanone, a frequently occurring compound in common foods such as banana and carrot. The aim was to study the inhibitory effects on prostaglandin production and COX-2 protein expression in tumour necrosis factor-α stimulated colon cancer cells (HT29) by radioimmunoassay and Western blotting. 2-Pentanone inhibited both prostaglandin production and COX-2 protein expression in human colon cancer cells. A concentration of 400 μmol/l 2-pentanone inhibited the prostaglandin production by 56.9±12.9% which is in the same range as the reference compound NS398 (59.8±7.6%). The two highest concentrations of 2-pentanone were further analyzed by Western blot, and 400 μmol/l and 200 μmol/l 2-pentanone resulted in a 53.3±9.6% and ±27.1% reduction of the COX-2 protein levels respectively. Further studies on flavouring compounds, for example 2-pentanone, as colon cancer chemopreventives would be very valuable, and such results may contribute to future dietary recommendations.

A vegetarian diet rich in phytochemicals may prevent colon carcinogenesis by affecting biochemical processes in the colonic mucosa. Compounds passing the digestive system reaching the colon could potentially be detected in fecal water. We previously reported that intact fecal water samples from human volunteers significantly decreased prostaglandin production and COX-2 protein expression in colonic cells. The aim with the present study was to further study the composition of the fecal waters, using NMR spectroscopy and multivariate data analysis, and to trace the COX-2 inhibiting activity. Intact fecal water samples and fractions thereof were analyzed for their ability to inhibit prostaglandin E2 production in the human colon cell line HT-29. The majority of the tested aqueous phases derived from intact fecal water showed ability to inhibit prostaglandin production in cells (13.8±1.34% inhibition, p=0.01). NMR analysis indicated the presence of significant quantities of amino acids and fatty acids. Major metabolites included; acetic acid, butanoic acid, propanoic acid, glutamic acid and alanine. Smaller amounts of glycine and fumaric acid, which are known to have anti-inflammatory and anti-tumorigenic properties, were also detected. This study describes for the first time NMR metabolomic analysis of fecal water from subjects on a vegetarian diet.