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.

There is convincing evidence that chemoprevention has the potential to be a major component of colorectal cancer control. Experimental, epidemiologic, and clinical studies provide evidence that nonsteroidal antiinflammatory drugs (NSAIDs), particularly the selective cyclooxygenase (COX)-2 inhibitors, including celecoxib and several phytochemicals, act as anticancer agents. However, several of these chemopreventive agents induce side effects at effective high dose levels. Low doses of atorvastatin and aspirin, or atorvastatin and celecoxib, or piroxicam and difluoromethylornithine administered in combination are more effective in inhibiting chemically induced colon adenocarcinomas in male F 344 rats than are high doses of these agents given individually.

Chemoprophylaxis of colon cancer.

Chemoprevention of colon cancer is emerging as an alternative to therapy with a broad potential for reducing cancer incidence in defined high-risk groups and the general population. Besides several chemopreventive agents in use and under investigation, D,L-alpha-difluoromethylornithine (DFMO) and piroxicam have been shown to effectively inhibit colon carcinogenesis in rodents. A variety of proliferation-related parameters have been suggested as potential intermediate markers of cancer risk that could be used to monitor the progress of chemoprevention in clinical trials. We have investigated the effect of chemopreventive agents, DFMO, and piroxicam on mucosal ornithine decarboxylase (ODC) and tyrosine-specific protein kinase (TPK) activities during different stages of azoxymethane (AOM)-induced colonic carcinogenesis in male F344 rats in order to examine the plausibility of using these enzymes as intermediate biochemical markers of colon cancer. Groups of male F344 rats were fed modified AIN-76A diets containing 0 or 150 ppm piroxicam or 4000 ppm DFMO and given s.c. injections of AOM dissolved in normal saline at a dose of 15 mg/kg body weight/week, once weekly, for 4 weeks. Vehicle control groups received s.c. equal volumes of normal saline. Groups of animals were then sacrificed at 0, 4, 16, 24, and 32 weeks after AOM or saline treatment, and their colonic mucosa was analyzed for ODC and TPK activities. AOM treatment significantly increased mucosal ODC as well as TPK activities. AOM-induced ODC and TPK activities were significantly suppressed by dietary DFMO progressively at all stages of colon carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

https://cebp.aacrjournals.org/content/cebp/1/5/405.full.pdf

Effect of chemopreventive agents on intermediate biomarkers during different stages of azoxymethane-induced colon carcinogenesis.

Human intervention studies have suggested an exciting synergistic action between calcium supplementation and aspirin intake in reducing the risk of colorectal cancer. The aim of this study was to determine whether such a synergy can be demonstrated on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) formation in mice and rats. Female CF-1 mice and male F344 rats were injected subcutaneously with AOM and then received diet treatments for 8 wk. The basal control diet contained high fat (20% mixed lipids by weight) and low calcium (1.4 mg/g diet) to mimic the average Western diet. The treatment diets contained enriched calcium (5.2 mg calcium/g diet), aspirin (0.2 mg aspirin/g diet), or calcium plus aspirin (5.2 mg calcium plus 0.2 mg aspirin/g diet). Treatment with calcium, aspirin, or their combination significantly decreased the number of total ACF and aberrant crypt per mouse (by 43-59%) or rat (by 23-38%), but statistically significant differences among the 3 groups were not observed. A hint of additivity between calcium and aspirin was observed in mice but not in rats. These results indicate that the combination of calcium and aspirin did not produce a synergistic effect on the ACF formation in AOM-treated mice and rats.

Effects of combination of calcium and aspirin on azoxymethane-induced aberrant crypt foci formation in the colons of mice and rats.

Metabolic epidemiological studies in humans and laboratory animal models demonstrate that consumption of diets high in fat and low in fiber excrete increased levels of 1,2-diacyl-sn-glycerol (DAG) and secondary bile acids such as deoxycholic acid (DA) and lithocholic acid that have been shown to promote colon carcinogenesis. The secondary bile acids and DAG have been shown to activate protein kinase C (PKC) and induce colonic cell proliferation. A large body of evidence indicates that iNOS, an inducible isoform of nitric oxide synthase, is over-expressed in human colon adenomas and in chemically-induced colon tumors of laboratory animals. However, the precise cascade of intracellular events that leads to the iNOS over-expression remains to be fully explored. In this study, we investigated the relationship between induction of iNOS and activation of the PKC pathway by DAG and DC, in an in vitro system using the rat intestinal cell line, RIE-1. As an initial step, we determined whether lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) modulate iNOS protein expression in RIE-1 cells. Treatment of RIE-1 cells with LPS and PMA for 4 h significantly elevated the iNOS protein expression. The induction of iNOS by the treatment with LPS/PMA was concentration- and time-dependent. Treatment with LPS/DAG or LPS/DC also caused iNOS over-expression in a concentration- and time-dependent fashion suggesting that DAG and DC induce iNOS activity in intestinal cells. Pretreatment with specific PKC inhibitors, bisindolylmaleimide I or Go 6976, inhibited LPS/PMA, LPS/DAG, or LPS/DC-induced iNOS expression and activity. Extracts of the cells treated with LPS/PMA, LPS/DAG or LPS/DC had a high iNOS activity compared to that of control (p<0.04 to p<0.0001). Taken together, our data suggest a possible role of colon tumor promoters, DAG and DC, for iNOS over-expression through activation of the PKC pathway.

Bandaru S. Reddy

Papers

Chemoprophylaxis of colon cancer.

Effect of chemopreventive agents on intermediate biomarkers during different stages of azoxymethane-induced colon carcinogenesis.

Effects of combination of calcium and aspirin on azoxymethane-induced aberrant crypt foci formation in the colons of mice and rats.

Modulation of inducible nitric oxide synthase expression in rat intestinal cells by colon tumor promoters.

Chemoprophylaxis of colon cancer