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.

/pdf/diet-rapidly-and-reproducibly-alters-the-human-gut-drvn0pi8vp.pdf

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.

Continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the relative risk of colorectal cancer in humans and decreases tumor yield in rodents treated with carcinogens. One well documented target for NSAIDs is prostaglandin endoperoxide synthase (cyclooxygenase) and two isoforms of this enzyme have been identified, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX enzymes produce eicosanoid products, some of which have recently been shown to activate transcription mediated by the nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARgamma), whose expression is largely restricted to adipose tissue. The present study was undertaken to determine if PPARgamma was expressed in colonic tumors. PPARgamma messenger RNA (mRNA) and protein levels were assayed in colonic tumors and normal adjacent mucosa, as well as in a variety of human colon cancer cell lines. There was a marked increase in PPARgamma RNA levels in four out of four of the colonic tumors compared to paired normal mucosa, where little expression of PPARgamma was detected. Western blotting analysis showed that PPARgamma protein was expressed in four out of five colonic tumor samples. PPARgamma was also expressed in a subset of polyps, and in certain human colon cancer cell lines as well. Additionally, we were able to demonstrate that an eicosanoid, 15 deoxy-delta12,14 PGJ2, transactivated transcription of a PPRE-driven promoter in CaCo-2 cells. Thus, we have shown that PPARgamma gene and protein expression is elevated in rodent colon tumors, in selected human colon cancer cell lines and that the PPARgamma receptor is functional in CaCo-2 cells. Since PPARgamma is a ligand-modulated transcription factor, it may provide a novel target for chemopreventive strategies for colorectal cancer.

/pdf/the-nuclear-eicosanoid-receptor-ppargamma-is-aberrantly-23l6yikoe5.pdf

The nuclear eicosanoid receptor, PPARgamma, is aberrantly expressed in colonic cancers.

The promoting effect of sodium deoxycholate (DC) on colon carcinogenesis was studied in female F344 germfree rats. Animals received intrarectal (ir) instillations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 4 weeks (total dose, 16 mg/rat), then weekly ir doses of DC (total dose, 3 g/rat); the rats were autopsied 52 weeks after the first injection. DC increased the number of MNNG-induced colon adenocarcinomas. No tumors were in the colons of germfree rats given DC alone. It was concluded that DC (present in high concentrations in human stools) had a promoting effect on colon carcinogenesis in rats.

Promoting Effect of Sodium Deoxycholate on Colon Adenocarcinomas in Germfree Rats

The effect of dietary menhaden oil containing omega-3 fatty acids and corn oil rich in omega-6 fatty acids fed during the initiation and/or postinitiation stages of colon carcinogenesis was investigated in male F344 rats. At 5 weeks of age, all animals were divided into seven groups (39 rats/group) and fed the semipurified diets containing 5% corn oil (LCO), 23.5% corn oil (HCO), or 18.5% menhaden oil plus 5% corn oil (HFO). At 7 weeks of age, all animals except the vehicle (normal saline)-treated groups were given two weekly s.c. injection of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight, once weekly. Three days after the second injection of AOM, groups of animals fed LCO, LCO, HCO, HCO, HCO, HFO, or HFO diets were transferred, respectively, to LCO, HCO, LCO, HCO, HFO, HCO, or HFO and continued on these diets until termination of the experiment. All animals were necropsied 42 weeks after carcinogen treatment. Body weights of animals fed various experimental diets during the initiation and postinitiation periods were comparable. As expected, the HCO diet fed during the postinitiation period significantly increased the AOM-induced incidence and multiplicity of colon adenocarcinomas, whereas the HCO diet fed during the initiation phase of carcinogenesis had no effect. Colon tumor incidence and multiplicity were significantly reduced in groups fed the HFO diet at either initiation and/or postinitiation phases of carcinogenesis as compared with those fed the HCO diet. Whereas the precise mechanisms producing the difference between the high menhaden oil (HFO) diet as compared with high corn oil (HCO) diet remain to be elucidated, it is likely that the effect during the initiation and postinitiation phases may be due to alteration in carcinogen metabolism and to modulation of prostaglandin synthesis, respectively.

https://cancerres.aacrjournals.org/content/canres/51/2/487.full.pdf

Effect of diets high in omega-3 and omega-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis.

Publisher Summary Nutrition is related to the development of cancer in three ways: (1) food additives or contaminants may act as carcinogens, cocarcinogens, or both; (2) nutrient deficiencies may lead to biochemical alterations that promote neoplastic processes; and (3) changes in the intake of selected macronutrients may produce metabolic and biochemical abnormalities, either directly or indirectly, which increase the risk for cancer. Specific carcinogens play a minor role as initiators in the relationship between nutrition and the development of cancer. This chapter covers six types of cancer: large bowel cancer, colon carcinogenesis, stomach cancer, cancer of the upper alimentary and respiratory tract, cancer of the pancreas, and breast cancer. In four of these—breast, large bowel, stomach, and head and neck—the epidemiologic evidence is overwhelming that nutritional factors have a major etiological role. Dietary factors are also implicated in the etiologies of the two remaining types of cancer—pancreas and prostate—but the epidemiologic evidence is not overwhelming. The chapter also presents an evaluation of the status of the relationship between nutrition and cancer in man, discusses the use of animal models to determine if the etiological factors established for man can be modified in an experimental setting, and makes recommendations for additional research and possible preventive measures.

Nutrition and its relationship to cancer

The effect of three levels of piroxicam and three levels of d,l-α-difluoromethylornithine (DFMO) fed individually and in combination during the postinitiation phase of carcinogenesis was studied in male F344 rats to generate a data base on the efficacy and synergistic and additive effects of these compounds as inhibitors of colon carcinogenesis. The maximum tolerated dose of DFMO was determined in male F344 rats and found to be 5000 ppm in the AIN-76A diet. Piroxicam at levels of 25, 75, and 150 ppm and DFMO at concentrations of 400, 1000, and 4000 ppm (20, 50, and 80% maximum tolerated dose) in AIN-76 diet were tested individually and in combinations. At 7 weeks of age, while the rats were consuming the control diet (AIN-76A), all animals except the vehicle (saline) — treated controls were given a single s.c. injection of azoxymethane (CAS: 25843-45-2) at a dose level of 29.6 mg/kg body weight to induce intestinal tumors. One week after azoxymethane injection, animals were transferred to their respective experimental diets containing piroxicam and DFMO. Fifty-six weeks after azoxymethane injection, all animals were necropsied and colon and small intestinal tumor incidences and multiplicity were compared among the various dietary groups. Feeding of diets containing 75 and 150 ppm piroxicam or 1000 and 4000 ppm DFMO significantly inhibited the incidence (percentage of animals with tumors) of colon adenocarcinomas compared to that of control diet. The multiplicity (number of tumors/rat) of adenocarcinomas was significantly inhibited in animals fed the 25, 75, and 150 ppm piroxicam or 400, 1000, and 4000 ppm DFMO diets. Results analyzed by the linear regression method suggested a dose-dependent inhibition in colon adenocarcinoma incidence with increasing levels of piroxicam or DFMO. The incidence and multiplicity of colon adenocarcinomas were significantly inhibited in animals fed the diets containing combinations of 25, 75, and 150 ppm piroxicam and 400, 1000, and 4000 ppm DFMO. Piroxicam and DFMO administered together had a stronger inhibitory effect than did those given individually. Piroxicam and DFMO when administered individually had no significant inhibitory effect on colon adenoma incidence and multiplicity; in contrast, combinations of these compounds significantly inhibited colon adenomas. No consistent differences were found in the incidence and multiplicity of small intestinal tumors among the dietary groups. The results of this study indicate that ( a ) increasing levels of piroxicam and DFMO in the diet inhibited colon adenocarcinomas in a dose-dependent manner, and ( b ) the administration of piroxicam and DFMO together was more effective than those administered individually in suppressing the colon adenoma and adenocarcinoma development.

https://cancerres.aacrjournals.org/content/canres/50/9/2562.full.pdf

Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet.

Bandaru S. Reddy

Papers

The nuclear eicosanoid receptor, PPARgamma, is aberrantly expressed in colonic cancers.

Promoting Effect of Sodium Deoxycholate on Colon Adenocarcinomas in Germfree Rats

Effect of diets high in omega-3 and omega-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis.

Nutrition and its relationship to cancer

Chemoprevention of colon carcinogenesis by concurrent administration of piroxicam, a nonsteroidal antiinflammatory drug with D,L-alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor, in diet.