Bilirubin in the Liver–Gut Signaling Axis

Bilirubin has been shown to reduce adiposity and fatty liver in the obese. Recent data show that bilirubin signals through nuclear receptors transcription factors and has the capacity to function as an antioxidant. The gut microbiota reduces bilirubin to urobilinogens in the intestine. Emerging data have shown that urobilinogens are reabsorbed in the intestine of the obese. However, their function remains elusive. Bilirubin derivatives contribute to pigmentation in urine and feces, and may have a major role in the gut–liver axis. Increasing unconjugated bilirubin levels in the plasma is a promising therapeutic for obesity and type 2 diabetes mellitus. Bilirubin is a component of the heme catabolic pathway that is essential for liver function and has been shown to reduce hepatic fat accumulation. High plasma bilirubin levels are reflective of liver disease due to an injurious effect on hepatocytes. In healthy liver, bilirubin is conjugated and excreted to the intestine and converted by microbes to urobilinoids, which are reduced to the predominant pigment in feces, stercobilin, or reabsorbed. The function of urobilinoids in the gut or their physiological relevance of reabsorption is not well understood. In this review, we discuss the relationship of hepatic bilirubin signaling to the intestinal microbiota and its regulation of the liver–gut axis, as well as its capacity to mediate these processes. Bilirubin is a component of the heme catabolic pathway that is essential for liver function and has been shown to reduce hepatic fat accumulation. High plasma bilirubin levels are reflective of liver disease due to an injurious effect on hepatocytes. In healthy liver, bilirubin is conjugated and excreted to the intestine and converted by microbes to urobilinoids, which are reduced to the predominant pigment in feces, stercobilin, or reabsorbed. The function of urobilinoids in the gut or their physiological relevance of reabsorption is not well understood. In this review, we discuss the relationship of hepatic bilirubin signaling to the intestinal microbiota and its regulation of the liver–gut axis, as well as its capacity to mediate these processes.