[What the (abdominal) surgeon needs to know on novel insights regarding cholic acids and their interaction with the...

The abdominal surgeon may have the opportunity to steadily learn on the (patho-)biochemical and (-)physiological consequences of his disease-related surgical activity (change of anatomy of the GI tract and its surrounding organs, medication and so on) if he refers closely to several medical disciplines as specifically indicated.

By means of a short compact overview based on (i) topic-related references from the scientific medical literature and (ii) own surgery-specific perceptions, interrelation of cholic acids (CA) with metabolism, in particular, with planned or performed (abdomino-)surgical procedures should be illustrated.

1. Surgery and biochemistry have a common and traditionally matured matter of consideration with regard to the consequences of an altered portal vein circulation and liver cirrhosis. 2. CA are (i) natural detergents, (ii) components of cholesterol-associated gall stones and (iii) essential signal molecules of intestine-liver metabolic interaction. CA and chenodesoxycholic acid [CDCA] dominate the CA pool with approximately 35 %. By conjugation of CA with taurine und glycine, its solubility is increased. The enterohepatic circulation minimizes the excretion of CA. 3. The generation of CA out of cholesterol within the liver (turnover/day: 0.2-0.6 g cholesterol) is controlled by cholesterol-7α-hydroxylase (CYP7A1). A toxic CA accumulation is prevented by a CA-induced repression of CYP7A1 expression and sulfation of CA (resulting in an increase of urine solubility). 4. CA show regulatory activities in the energy, glucose, lipid and lipoprotein metabolism and connate immune system. By binding of the CA to the farnesoid X-nuclear receptor [FXR] and the membranous G-protein-coupled CA receptor-1 [GPBAR1, TGR5], mannifold effects within the fat and carbohydrate metabolism are induced. 5. CA trigger the expression of the iodothyronine-dejodinase (DIO2) within the brown fat tissue and skelet muscles by activation of the GPBAR1-MAPK signal pathways. Hence, thyroxine (T₄) is transformed to trijodthyronine (T₃) and, subsequently, fat oxidation and thermogenesis are increased. 6. CA change the intestinal microbioma by bacteriolytic activities and, on the other hand, the CA profile is modulated by the microbioma. Typical microbial effects of the CA pool are (i) separation of glycine and taurine residuals of conjugated CA by "bile salt hydrolases" and (ii) chemical modification of free, primary CA by re-amidation, oxidation-reduction, esterification and desulfation. 7. CA inhibit the endotoxin-based inflammatory response induced by lipopolysaccharides (LPS; membranous component of gram-negative bacteria). Via binding of CA to macrophages-associated receptors (GPBAR1 and FXR), (i) the LPS-induced proinflammatory cytokine generation is reduced and the expression of antiinflammatory IL-10 is promoted. In addition, (ii) white-blood cell "trafficking" is regulated and (iii) inflammasoma is activated by macrophages and neutrophil granulocytes. 8. The body weight-independent changes after bariatric surgery (e. g., in case of "Roux-en-Y gastric bypass" [RYGB]) correlate with an increased CA serum level and an altered intestinal CA profile. The latter leads secundarily to a modification of the microbioma. RYGB has - among others - positive effects onto the carbohydrate metabolism. Thus, insulin sensitivity of the liver is improved and the secretion of the glucagon-like peptide 1 is enhanced.

CA are a parade example for metabolic regulators, the interactions of which have an impact onto various (patho-)biochemical and (-)physiological processes, (abdomino-)surgically relevant diseases and (abdomino-)surgical measures. Their biochemical/physiological activities and insight into associated molecular processes should be part of the medical and scientific skills of a modern (abdominal) surgeon with a developed pathophysiological expertise.