Enteric Infection with Citrobacter rodentium Induces Coagulative Liver Necrosis and Hepatic Inflammation Prior to Peak Infection and Colonic Disease

Acute and chronic forms of inflammation are known to affect liver responses and susceptibility to disease and injury. Furthermore, intestinal microbiota has been shown critical in mediating inflammatory host responses in various animal models. Using C. rodentium, a known enteric bacterial pathogen, we examined liver responses to gastrointestinal infection at various stages of disease pathogenesis. For the first time, to our knowledge, we show distinct liver pathology associated with enteric infection with C. rodentium in C57BL/6 mice, characterized by increased inflammation and hepatitis index scores as well as prominent periportal hepatocellular coagulative necrosis indicative of thrombotic ischemic injury in a subset of animals during the early course of C. rodentium pathogenesis. Histologic changes in the liver correlated with serum elevation of liver transaminases, systemic and liver resident cytokines, as well as signal transduction changes prior to peak bacterial colonization and colonic disease. C. rodentium infection in C57BL/6 mice provides a potentially useful model to study acute liver injury and inflammatory stress under conditions of gastrointestinal infection analogous to enteropathogenic E. coli infection in humans.United States. Army Research Office (Institute for Soldier Nanotechnology grant 6915539 (SRT))National Institutes of Health (U.S.) (Grant P01 CA026731)National Institutes of Health (U.S.) (Grant P30 ES02109)National Institutes of Health (U.S.) (Toxicology Training grant ES-070220

Low activities of digestive enzymes in the guts of herbivorous grouse (Aves: Tetraoninae)

Avian herbivores face the exceptional challenge of digesting recalcitrant plant material while under the selective pressure to reduce gut mass as an adaptation for fight. One mechanism by which avian herbivores may overcome this challenge is to maintain high activities of intestinal enzymes that facilitate the digestion and absorption of nutrients. However, previous studies in herbivorous animals provide equivocal evidence as to how activities of digestive enzymes may be adapted to herbivorous diets. For example, “rate-maximizing” herbivores generally exhibit rapid digesta transit times and high activities of digestive enzymes. Conversely, “yield-maximizing” herbivores utilize long gut retention times and express lower activities of digestive enzymes. Here, we investigated the activities of digestive enzymes (maltase, sucrase, aminopeptidase-N) in the guts of herbivorous grouse (Aves: Tetraoninae) and compared them to activities measured in several other avian species. We found that several grouse species exhibit activities of enzymes that are dramatically lower than those measured in other birds. We propose that grouse may use a “yield-maximizing” strategy of digestion, which is characterized by relatively long gut retention times and generally lower enzyme activities. These low activities of intestinal digestive enzyme could have ecological and evolutionary consequences, as grouse regularly consume plants with compounds known to inhibit digestive enzymes. However, more comprehensive studies on passage rates, digestibility, and microbial contributions will be necessary to understand the full process of digestion in herbivorous birds.acceptedVersio