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...

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Role of nrf2 in oxidative stress and toxicity.

The effect of dietary alfalfa, pectin, and wheat bran on colon carcinogenesis was studied in female inbred F344 rats. Weanling rats were fed semipurified diets containing 0 or 15% alfalfa, pectin, or wheat bran. At 7 weeks of age, all animals except controls were given azoxymethane (AOM) sc at a dose rate of 8 mg/kg body weight/week for 10 weeks or methylnitrosourea (MNU) intrarectally at a dose rate of 2 mg/rat twice a week for 3 weeks. The AOM-treated group was autopsied 40 weeks and the MNU-treated group 30 weeks after the first injection of the carcinogen. No tumors were observed in the colon or other organs of untreated rats fed the various diets. The animals fed the alfalfa diet and treated with MNU had a higher incidence of colon tumors than did those fed the control diet or the diets containing pectin or wheat bran. The incidence of MNU-induced colon tumors did not differ between the animals fed the control diet or the diets containing pectin or wheat bran. However, the incidence of AOM-induced colon tumors in rats fed diets containing pectin or wheat bran was lower than that in rats fed the control diet or the alfalfa diet. These results thus indicate that the effect of fiber in colon carcinogenesis depends on the type of fiber and, possibly, the fiber's mode of action.

Effect of Dietary Alfalfa, Pectin, and Wheat Bran on Azoxymethane- or Methylnitrosourea-Induced Colon Carcinogenesis in F344 Rats

Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects.

The inhibitory effect of 40 and 80% maximum tolerated dose (MTD) levels of piroxicam, ibuprofen, ketoprofen and glycyrrhetinic acid on colon carcinogenesis was investigated in male F344 rats. The MTD levels of piroxicam, ibuprofen, ketoprofen and glycyrrhetinic acid as determined in male F344 rats were 500, 500, 250 and 3000 p.p.m. respectively. At 5 weeks of age, groups of male F344 rats were fed the control (AIN-76A) diet and 40 and 80% MTD levels of each test agent in AIN-76A diet. At 7 weeks of age, all animals except the vehicle (saline)-treated controls received azoxymethane (AOM) at a dose rate of 15 mg/kg body wt, once weekly for 2 weeks. All animals were necropsied 50 weeks after the second AOM injection and colon tumor incidences were compared among the groups fed the control diet and chemopreventive agents. Animals fed 400 (80% MTD) and 200 p.p.m. (40% MTD) of piroxicam, 400 p.p.m. (80% MTD) of ibuprofen and 200 p.p.m. (80% MTD) of ketoprofen showed a significant inhibition of colon tumorigenesis as compared to those fed the control diet. Results analyzed by the linear regression method suggested a dose-dependent inhibition of colon carcinogenesis with increasing levels of piroxicam or ibuprofen. In contrast, glycyrrhetinic acid had no measurable chemopreventive effect on colon carcinogenesis.

Inhibition of colon carcinogenesis by prostaglandin synthesis inhibitors and related compounds

Cancer chemopreventive agent sulforaphane (SFN) and dibenzoylmethane (DBM) showed antitumorigenesis effects in several rodent carcinogenesis models. In this study, we investigated the cancer chemopreventive effects and the underlying molecular mechanisms of dietary administration of SFN and DBM alone or in combination in the ApcMin/+ mice model. Male ApcMin/+ mice (12 per group) at age of 5 weeks were given control AIN-76A diet, diets containing 600 ppm SFN and 1.0% DBM, or a combination of 300 ppm SFN and 0.5% DBM for 10 weeks. Mice were then sacrificed, and tumor numbers and size were examined. Microarray analysis, Western blotting, ELISA, and immunohistochemical staining were done to investigate the underlying molecular mechanisms of cancer chemopreventive effects of SFN and DBM. Dietary administrations of SFN and DBM alone or in combination significantly inhibited the development of intestinal adenomas by 48% (P=0.002), 50% (P=0.001), and 57% (P<0.001), respectively. Dietary administration of 600 ppm SFN and 1.0% DBM also reduced colon tumor numbers by 80% (P=0.016) and 60% (P=0.103), respectively, whereas the combination of SFN and DBM treatment blocked the colon tumor development (P=0.002). Both SFN and DBM treatments resulted in decreased levels of prostaglandin E2 or leukotriene B4 in intestinal polyps or apparently normal mucosa. Treatments also led to the inhibition of cell survival and growth-related signaling pathways (such as Akt and extracellular signal-regulated kinase) or biomarkers (such as cyclooxygenase-2, proliferating cell nuclear antigen, cleaved caspases, cyclin D1, and p21). In conclusion, our results showed that both SFN and DBM alone as well as their combination are potent natural dietary compounds for chemoprevention of gastrointestinal cancers.

https://cancerres.aacrjournals.org/content/canres/67/20/9937.full.pdf

Chemoprevention of Familial Adenomatous Polyposis by Natural Dietary Compounds Sulforaphane and Dibenzoylmethane Alone and in Combination in ApcMin/+ Mouse

Purpose: Epidemiologicstudies have linked the consumption of fruits and vegetables to reduced risk of several types of cancer. Laboratory animal model studies have provided evidence that stilbenes, phenoliccompounds present in grapes and blueberries, play a role in inhibiting the risk of certain cancers. Pterostilbene, a naturally occurring stilbene from blueberries, was tested for its preventive activity against colon carcinogenesis. Experimental Design: Experiments were designed to study the inhibitory effect of pterostil- bene against the formation of azoxymethane-induced colonic aberrant crypt foci (ACF) preneo- plasticlesions in male F344 rats. Beginning at 7 weeks of age, rats were treated with azoxymethane (15 mg/kg body weight s.c., once weekly for 2 weeks). One day after the second azoxymethane treatment, rats were fed experimental diets containing 0 or 40 ppm of pterostil- bene. At 8 weeks after the second azoxymethane treatment, all rats were sacrificed, and colons were evaluated for ACF formation and for inhibition of inducible nitric oxide synthase (iNOS) and proliferating cell nuclear antigen. Effects on mucin MUC2 were also determined. Results: Administration of pterostilbene for 8 weeks significantly suppressed azoxymethane- induced formation of ACF (57% inhibition, P < 0.001) and multiple clusters of aberrant crypts (29% inhibition, P < 0.01). Importantly, dietary pterostilbene also suppressed azoxymethane- induced colonic cell proliferation and iNOS expression. Inhibition of iNOS expression by pterostil- bene was confirmed in cultured human colon cancer cells. Conclusions: The results of the present study suggest that pterostilbene, a compound present in blueberries, is of great interest for the prevention of colon cancer.

/pdf/pterostilbene-an-active-constituent-of-blueberries-3b2jt9vsp6.pdf

Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats.

Bandaru S. Reddy

Papers

Effect of Dietary Alfalfa, Pectin, and Wheat Bran on Azoxymethane- or Methylnitrosourea-Induced Colon Carcinogenesis in F344 Rats

Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects.

Inhibition of colon carcinogenesis by prostaglandin synthesis inhibitors and related compounds

Chemoprevention of Familial Adenomatous Polyposis by Natural Dietary Compounds Sulforaphane and Dibenzoylmethane Alone and in Combination in ApcMin/+ Mouse

Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats.