[12-14] The acquired flora in such artificially colonized animal models remains stable over a long period. Further, the animals naturally pass their flora to their progeny.[15] However, these models have a relatively limited bacterial diversity than the flora in human gut. In this model, mouse or human fecal material is used to colonize the gut of GF animals. The flora in such animals also show long-term stability and are passed on to offsprings. These models are also useful in studying the alterations in gut flora and intestinal ecosystem

during physiological and pharmacological interventions, PARP inhibitor such as antibiotic administration,[16] circumventing the ethical issues associated with similar studies in humans. Another advantage of such models relates to avoidance

of confounding by variations in human diet, lifestyle patterns, and host genetics. Although these models more closely resemble http://www.selleckchem.com/products/azd9291.html the human situation than the mono- or bi- and poly-associated models, these may still not fully replicate the human situation. For instance, feces from humans and human flora-associated animals differ significantly in concentration of short-chain fatty acids, despite being similar in several other characteristics.[17] Liver has a dual blood supply with nearly 70% of its blood coming from intestines through the portal circulation and the remaining through the hepatic Thiamet G artery. Although the intestinal mucosa acts as an effective barrier against translocation of microbes and microbial

products from the gut to the circulation, small quantities of these do enter the portal venous blood. Liver, being strategically located between highly contaminated bowel and sterile systemic circulation, works as a filter. Immune cells in hepatic sinusoids effectively remove bacteria and bacterial products from the portal blood,[18] protecting the systemic circulation from endotoxemia. Liver is also rich in a variety of innate immune cells, namely natural killer cells (NK cells), NK T cells, Kupffer cells, and hepatic stellate cells. These cells serve to maintain a sensitive balance between protective immune response against exogenous antigens and immune tolerance; the latter is particularly important because excessive activation of hepatic immune cells in response to exogenous antigens may induce inflammation, autoimmune phenomena, fibrosis, or carcinogenesis in the liver. Alterations in nature and number of bacterial species in the gut microflora or their increased translocation may also disturb this fine balance and lead to liver injury, particularly when “liver tolerance” to bacterial products has been breached.