Cholemia

Abstract: Owing to their health benefits, dietary fermentable fibers, such as refined inulin, are increasingly fortified in processed foods to enhance their nutritional value. However, we previously demonstrated that when inulin was fed to Toll-like receptor 5 deficient (T5KO) mice susceptible to dysbiosis, a subset of them developed cholestasis and subsequently liver cancer in a gut microbiota-dependent manner. Therefore, we hypothesized that clearance of bacterial taxa, and thereby gut metabolites, involved in the onset and progression to liver cancer could abate the disease in these mice. Such a reshaping of microbiota by vancomycin treatment was sufficient to halt the development of liver cancer in inulin-fed T5KO mice; however, this intervention did not remedy disease penetrance for cholestatic liver injury and its sequelae, including hyperbilirubinemia, hypolipidemia, cholemia and liver fibrosis. Selective depletion of gut bacterial communities was observed in vancomycin-treated mice, including Gram-positive Lachnospiraceae and Ruminococcaceae belonging to the phylum Firmicutes, Bifidobacteria of the phylum Actinobacteria, which ferment fibers, and Clostridium cluster XIVa, which produce secondary bile acids. Lack of liver cancer in vancomycin-treated mice strongly correlated with the substantial loss of secondary bile acids in circulation. Although cholemia was unabated by vancomycin, the composition of serum bile acids shifted toward an abundance of hydrophilic primary bile acids, denoted by the increase in conjugated-to-unconjugated bile acid ratio. Taken together, the present study suggests that microbiotal regulation of bile acid metabolism is one of the critical mediators of fermentable fiber-induced liver cancer in dysbiotic mice.

Abstract: It has been known for four decades that patients with obstructive jaundice are at a high risk for postoperative acute renal failure (1–4). These patients also have greater falls in blood pressure following modest blood loss than patients without jaundice. The search for the cause of these complications of obstructive jaundice and attempts at prophylactic treatment in jaundiced patients undergoing surgery have prompted extensive experiments on animals with chronic bile duct ligation (CBDL) or animals in which the entire bile flow is diverted from the common bile duct to the systemic circulation-choledochocaval anastomosis (CDCA). While extrapolation to humans of conclusions obtained in animal studies should be made with caution, a growing body of evidence now suggests that bile constituents (e.g., bile acids, bilirubin, cholesterol) do not exert a direct nephrotoxic effect. Rather, retention of bile during cholestatic jaundice has deleterious effects on cardiovascular function and on blood volume. This, in turn, sensitizes the kidney to prerenal failure and acute tubular necrosis in postsurgical patients with obstructive jaundice.

Abstract: Kidney injury in the context of cholestatic liver dysfunction is not uncommon; this has been historically referred to as cholemic nephrosis implying a direct deleterious renal effect of cholemia. However, scepticism about the exact role that bile and its constituents play in this injury has led to the disappearance of the term. We describe a case of severe AKI due to bile nephropathy with bile casts in flucloxacillin-induced liver dysfunction. We also discuss the recent literature reviving the concept of bile nephropathy.