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 effect of a mixed Western, high meat diet or a nonmeat diet on the intestinal bacterial beta-glucuronidase activity was studied in human volunteers. This enzyme was significantly higher in stools of subjects on a high meat diet as compared to the nonmeat regimen. Thus, intestinal flora of subjects on a high meat diet was more able to hydrolyze glucuronide conjugates than that of individuals on a nonmeat diet. This, in turn, may raise the amount of substances, such as carcinogens, within the colonic lumen.

https://science.sciencemag.org/content/sci/183/4123/416.full.pdf

Fecal Bacterial β-Glucuronidase: Control by Diet

The effect of intestinal microflora on the sensitivity of the colon to the carcinogenic effect of 1,2-dimethylhydrazine (DMH), which needs metabolic activation, and N -methyl- N ′-nitro- N -nitrosoguanidine a direct-acting carcinogen, was studied using Fischer germ-free and conventional female rats. None of the germ-free rats that received s.c. injections of DMH, 10 mg/week/kg body weight for 20 weeks and autopsied after the last injection showed colon tumors, whereas 17% of the conventional rats treated similarly developed adenocarcinomas of the colon. At 20 weeks after the last injection of DMH, 11% of germ-free rats developed adenomas, whereas 25% of the conventional rats showed colonic tumors, 67% of which were adenocarcinomas and 34% of which were adenomas. In contrast to DMH, i.r. injection of N -methyl- N ′-nitro- N -nitrosoguanidine (total dose, 48 mg in 20 weeks) nearly doubled the multiple colonic tumors in germ-free rats compared to conventional controls. It is concluded that the intestinal microflora play a modifying role in colon carcinogenesis by DMH.

https://cancerres.aacrjournals.org/content/canres/34/9/2368.full.pdf

Colon carcinogenesis in germ-free rats with 1,2-dimethylhydrazine and N-methyl-n'-nitro-N-nitrosoguanidine.

Epidemiologic and experimental studies suggest that consumption of fermented milk products and lactic bacterial cultures that are used to ferment the dairy products, decrease the incidence of certain types of cancer. The present study was designed to determine the effect of lyophilized cultures of Bifidobacterium longum (B. longum), a lactic bacteria, on the azoxymethane (AOM)-induced preneoplastic lesions such as aberrant crypt foci (ACF) formation in the colon and on fecal bacterial beta-glucuronidase activity in male F344 rats. At 5 weeks of age, groups of animals were fed the AIN-76A (control) and the experimental diets containing 1.5% and 3% lyophilized cultures of B. longum. At 10 weeks of age, all animals received sc injection of AOM dissolved in normal saline at a dose rate of 20 mg/kg body wt, once weekly for 2 weeks. The animals were necropsied 6 weeks after the last AOM injection, and the ACF were visualized under light microscopy in the formalin-fixed, unsectioned methylene blue-stained colons where they were distinguished by their increased size, more prominent epithelial cells, and pericryptal space. The cecal contents were analyzed for bacterial beta-glucuronidase activity. The feeding of lyophilized cultures of B. longum significantly inhibited the ACF formation (53%) and the crypt multiplicity in the colon. A significant decrease in the fecal bacterial beta-glucuronidase was also observed in the animals fed the diets containing Bifidobacterium supplements as compared with control diet. These results demonstrate that B. longum in diet influences the metabolic activity of certain types of intestinal microflora that are involved in the production of beta-glucuronidase. Furthermore, the findings also suggest that B. longum supplements inhibit ACF formation, an early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

Inhibitory effect of Bifidobacterium longum cultures on the azoxymethane-induced aberrant crypt foci formation and fecal bacterial beta-glucuronidase.

Identification of Nrf2-regulated genes induced by chemopreventive isothiocyanate PEITC by oligonucleotide microarray.

The promoting effect of sodium lithocholate, cholesterol, cholesterol-5α,6α-epoxide (cholesterol epoxide), and cholestane-3β,5α,6β-triol (triol) on colon carcinogenesis was studied in female Fischer (F-344) conventional and germ-free rats. Evaluation of these compounds for their colon tumor-promoting activity in a germ-free animal system would indicate whether further modification of these compounds by gut microflora is required for tumor promotion. At 7 weeks of age, groups of germ-free and conventional rats were given intrarectal instillations of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) at a dose rate of 2.5 mg/rat, twice a week for 2 weeks, and then were given intrarectal doses of sodium lithocholate, cholesterol, cholesterol epoxide, or triol at a dose rate of 20 mg/rat 3 times a week for 46 weeks; other groups received MNNG for 2 weeks and vehicle thereafter for 46 weeks or lithocholate or cholesterol metabolites alone for 48 weeks. No tumors were detected in rats given sodium lithocholate, cholesterol, cholesterol epoxide, or triol alone, which suggested that these compounds, or their microbially modified metabolites, were not carcinogenic to colon mucosa under our experimental conditions. Sodium lithocholate increased MNNG-induced colon tumor incidence in both germ-free and conventional rats. The colon tumor incidence was similar in the MNNG, MNNG-plus-cholesterol, MNNG-plus-cholesterol epoxide and MNNG-plus-triol groups. The results obtained in germ-free rats also indicate that lithocholate without being further modified by the gut microflora acts as a colon tumor promoter. It is concluded that sodium lithocholate, but not cholesterol, cholesterol epoxide, triol, or their microbial products, had a promoting effect in MNNG-induced colon carcinogenesis in rats.

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Bandaru S. Reddy

Papers

Fecal Bacterial β-Glucuronidase: Control by Diet

Colon carcinogenesis in germ-free rats with 1,2-dimethylhydrazine and N-methyl-n'-nitro-N-nitrosoguanidine.

Inhibitory effect of Bifidobacterium longum cultures on the azoxymethane-induced aberrant crypt foci formation and fecal bacterial beta-glucuronidase.

Identification of Nrf2-regulated genes induced by chemopreventive isothiocyanate PEITC by oligonucleotide microarray.

Effect of Cholesterol Metabolites and Promoting Effect of Lithocholic Acid in Colon Carcinogenesis in Germ-free and Conventional F344 Rats