Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

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Diet rapidly and reproducibly alters the human gut microbiome

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(00)04046-0.pdf

Inflammation and cancer: back to Virchow?

The importance of the ratio of omega-6/omega-3 essential fatty acids.

http://envismadrasuniv.org/Physiology/pdf/Gut%20flora%20in%20health%20and%20disease.pdf

Gut flora in health and disease

Organismal life encounters reactive oxidants from internal metabolism and environmental toxicant exposure. Reactive oxygen and nitrogen species cause oxidative stress and are traditionally viewed as being harmful. On the other hand, controlled production of oxidants in normal cells serves useful purposes to regulate signaling pathways. Reactive oxidants are counterbalanced by complex antioxidant defense systems regulated by a web of pathways to ensure that the response to oxidants is adequate for the body's needs. A recurrent theme in oxidant signaling and antioxidant defense is reactive cysteine thiol–based redox signaling. The nuclear factor erythroid 2–related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure. This review discusses the impact of Nrf2 on oxidative stress and toxicity and how...

/pdf/role-of-nrf2-in-oxidative-stress-and-toxicity-2utmvoa3ko.pdf

Role of nrf2 in oxidative stress and toxicity.

The promoting effect of sodium cholate or sodium chenodeoxycholate on colon carcinogenesis was studied in female F344 germ-free and conventional rats. Both germ-free and conventional rats received intrarectal instillations of N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG) for 2 weeks (total dose, 8 mg/rat) and then intrarectal doses of sodium cholate or sodium chenodeoxycholate (20 mg/rat/dose) three times a week for 46 weeks; other groups received MNNG for 2 weeks and vehicle thereafter for 46 weeks or bile acids alone for 48 weeks. Sodium cholate or sodium chenodeoxycholate increased MNNG-induced adenocarcinomas and adenomas in germ-free rats, whereas in conventional rats these bile acids induced more adenomas. Conventional rats treated with MNNG + sodium cholate or MNNG + sodium chenodeoxycholate had a higher incidence ( p 0.05) frequency of colon tumors than did those given MNNG alone. No tumors were detected in the colons of germ-free and conventional rats given sodium cholate or sodium chenodeoxycholate alone. It is concluded that sodium cholate or sodium chenodeoxycholate had a promoting effect in colon carcinogenesis in rats evoked by MNNG.

https://cancerres.aacrjournals.org/content/canres/37/9/3238.full.pdf

Promoting Effect of Bile Acids in Colon Carcinogenesis in Germ-free and Conventional F344 Rats

Epidemiological and laboratory studies indicate an inverse relationship between the risk of colon cancer development and intake of nonsteroidal antiinflammatory agents, including aspirin. One of the mechanisms by which nonsteroidal antiinflammatory agents inhibit colon carcinogenesis is through the inhibition of prostaglandin production by cyclooxygenase isozymes (COX-1 and COX-2). Overexpression of COX-2 has been observed in colon tumors. Thus, selective inhibitors of COX-2 could potentially serve as chemopreventive agents. We have assessed the chemopreventive properties of SC-58635, a COX-2 inhibitor, and of sulindac, as a positive control, in a double-blind study, using azoxymethane-induced colonic aberrant crypt foci (ACF) as a measure of efficacy. Five-week-old male F344 rats were fed the control diet (modified AIN-76A) or experimental diets containing 150 or 1500 ppm SC-58635, 320 ppm sulindac, or 1500 ppm placebo. Two weeks later, all animals except those in vehicle (normal saline)-treated groups were s.c. injected with azoxymethane (15 mg/kg of body weight, once weekly for 2 weeks). At 16 weeks of age, all rats were sacrificed and colons were evaluated for ACF. As expected, dietary administration of sulindac suppressed ACF development as such and reduced crypt multiplicity in terms of number of aberrant crypts/ focus. Administration of 1500 ppm SC-58635 inhibited total ACF induction and crypt multiplicity by about 40-49%. Our finding that SC-58635 significantly suppressed colonic ACF formation and crypt multiplicity strengthens the hypothesis that a selective COX-2 inhibitor possesses chemopreventive activity against colon carcinogenesis.

https://cancerres.aacrjournals.org/content/canres/56/20/4566.full.pdf

Evaluation of Cyclooxygenase-2 Inhibitor for Potential Chemopreventive Properties in Colon Carcinogenesis

Epidemiological and laboratory animal model studies have suggested that nonsteroidal anti-inflammatory drugs reduce the risk of development of colon cancer. The present study was designed to investigate the chemopreventive action of 160 and 320 ppm (equivalent to 40 and 80% maximum tolerated doses) sulindac, a nonsteroidal anti-inflammatory drug, fed during initiation and postinitiation stages and 320 ppm sulindac fed during promotion/progression stages of azoxymethane-induced colon carcinogenesis in male F344 rats. Also investigated was the modulating effect of this agent on the colonic mucosal and tumor phospholipase A2, phosphatidylinositol-specific phospholipase C, lipoxygenase, and cyclooxygenase activities. At 5 weeks of age, groups of male F344 rats were fed control diet or diets containing 160 and 320 ppm of sulindac. At 7 weeks of age, all animals except those in the vehicle-treated groups were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight/week. Animals intended for tumor promotion/progression study were administered 320 ppm of sulindac in diet starting at 14 weeks after a second azoxymethane treatment. All animals continued on their respective dietary regimen until the termination of the experiment at 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Colonic mucosa and tumors were analyzed for phospholipase A2, phosphatidylinositol-specific phospholipase C, prostaglandin E2, cyclooxygenase, and lipoxygenase activities. The levels of sulindac and its metabolites in stomach, cecal, and fecal contents and in serum were analyzed. The results indicate that dietary sulindac at 160 and 320 ppm levels inhibited the incidence of invasive and noninvasive adenocarcinomas of the colon (P 52-62% compared to the control diet. Dietary sulindac significantly decreased the activities of phosphatidylinositol-specific phospholipase C (32-51%) and levels of prostaglandin E2 (> 40%) in the colonic mucosa and tumors, but it had no significant (P > 0.05) effect on phospholipase A2 activity. The formation of cyclooxygenase metabolites, particularly prostaglandin E2, prostaglandin F2 alpha, prostaglandin D2, 6-ketoprostaglandin F1 alpha, and thromboxane B2, and lipoxygenase metabolites such as 8(S)- and 12(S)-hydroxyeicosatetraenoic acids were significantly reduced in colonic mucosa and tumors of animals fed 320 ppm sulindac.(ABSTRACT TRUNCATED AT 400 WORDS)

http://cancerres.aacrjournals.org/content/canres/55/7/1464.full.pdf

Chemoprevention of colon carcinogenesis by sulindac, a nonsteroidal anti-inflammatory agent.

Large-Bowel Carcinogenesis: Fecal Constituents of Populations With Diverse Incidence Rates of Colon Cancer

Because of potential significance of bile acids and cholesterol metabolites in the pathogenesis of colon cancer, fecal neutral sterols, and bile acids were determined in patients with colon cancer, adenomatous polyps or other digestive diseases and American or Japanese controls. The fecal excretion of cholesterol, coprostanol, coprostanone, total bile acids, deoxycholic acid, lithocholic acid was higher in patients with colon cancer and patients with adenomatous polyps compared to normal American and Japanese controls as well as patients with other digestive diseases. Patients with other digestive diseases excreted comparable levels of fecal bile acids and cholesterol metabolites compared to normal American controls; Japanese controls excreted reduced levels compared to normal American controls. These findings suggest that possible interactions between bile acids and cholesterol metabolites and colonic epithelial cells may be relevant in colon carcinogenesis.

Bandaru S. Reddy

Papers

Promoting Effect of Bile Acids in Colon Carcinogenesis in Germ-free and Conventional F344 Rats

Evaluation of Cyclooxygenase-2 Inhibitor for Potential Chemopreventive Properties in Colon Carcinogenesis

Chemoprevention of colon carcinogenesis by sulindac, a nonsteroidal anti-inflammatory agent.

Large-Bowel Carcinogenesis: Fecal Constituents of Populations With Diverse Incidence Rates of Colon Cancer

Metabolic epidemiology of colon cancer: Fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps