As an essential metabolic molecule, bile acids regulate triglyceride, cholesterol, energy metabolism. Bariatric surgery offers a treatment that can reduce weight and induce metabolic syndrome, but the mechanism is still unclear. New researches reveal that serum bile acids are elevated after surgery, as well as the improvement of metabolic disease. The surgery changes gastrointestinal tract, resulting in a short circuiting of the enterohepatic circulation of bile acids. Here we review the bile acids metabolism and their effect after bariatric surgery.
Bariatric Surgery ; Bile Acids and Salts ; Enterohepatic Circulation ; Gastrointestinal Tract ; Humans ; Lipid Metabolism ; Metabolic Syndrome

PURPOSE: Cholestylamine has been shown to release chloride ion and absorbs bile acid in the intestine, forming a nonabsorbable complex preventing enterohepatic circulation. The purpose of this study is to clarify the value of cholestylamine and the adequate dosage, in combination with phototherapy, as well as to confirm whether it shorten the duration of hospitalization. METHODS: Total 80 full-term neonates with a total bilirubin level greater than 12mg/dL were studied. The neonates were randomly divided into four groups : (1) Only phototherapy group (A)(2) 250mg/kg/day cholestylamine with phototherapy group (B)(3) 500mg/kg/day cholestylamine with phototherapy group (C)(4) 1000mg/kg/day cholestylamine with phototherapy group (D). RESULTS: Forty-eight hours, 72 hours and 96 hours after the beginning of the study, the mean bilirubin level among the B, C, D groups significantly diminished than A group (P<0.05). The duration of phototherapy and hospitalization significantly diminished in the D group. After phototherapy, finished mean bilirubin level was markedly diminished in the D group. CONCLUSION: The data revealed that oral administration of cholestylamine (especially 1000mg/kg/ day cholestylamine with phototherapy group : D) not only increased the efficacy of phototherapy, but also shortened the duration of phototherapy.
Administration, Oral* ; Bile ; Bilirubin ; Enterohepatic Circulation ; Hospitalization ; Humans ; Hyperbilirubinemia, Neonatal* ; Infant, Newborn ; Intestines ; Jaundice, Neonatal ; Phototherapy*

A significant proportion of chronic constipation patients are dissatisfied with their treatment. Recently, a number of new medications have been introduced for patients refractory to conventional laxatives, such as prucalopride, lubiprostone, linaclotide, and elobixibat. Prucalopride is a novel gastrointestinal prokinetic agent that acts as a 5-hydroxytryptamine type 4 (5-HT4) agonist. Compared with older nonselective 5-HT4 agonists, the higher selectivity of prucalopride for 5-HT4 receptors can reduce the risk of significant adverse cardiovascular events. Prucalopride improves stool frequency and consistency, and reduces the need for rescue medications. Lubiprostone, a chloride channel activator, increases the secretion of intestinal fluid, improves the stool frequency and consistency, and reduces straining. Linaclotide, a guanylate cyclase-C agonist, is effective in treating patients with chronic constipation and its effect on visceral sensitivity, as shown mainly in animal studies, provides an attractive pharmaceutical option for patients with irritable bowel syndrome with constipation. Elobixibat is an ileal sodium-dependent bile acid transporter inhibitor that blocks the enterohepatic circulation of bile acids, increasing the bile acid concentration in the intestine, which accelerates colonic transit and softens the stool. A phase III trial of the treatment of chronic constipation and irritable bowel syndrome with constipation is underway. The clinical application of new-generation laxatives will contribute to the management of chronic constipation refractory to conventional laxatives.
Animals ; Bile ; Bile Acids and Salts ; Chloride Channels ; Colon ; Constipation ; Enterohepatic Circulation ; Humans ; Intestines ; Irritable Bowel Syndrome ; Laxatives* ; Receptors, Serotonin, 5-HT4 ; Serotonin ; Serotonin 5-HT4 Receptor Agonists ; Lubiprostone

Cholelithiasis in infancy is a rare disorder. A number of conditions that occur in the neonatal period predispose to the development of cholelithiasis. Cholelithiasis is more marked in the premature than adult, because of the immaturity of the enterohepatic circulation of bile acids which renders the newborn more susceptible to the cholestatic effect of total parenteral nutrition (TPN). Parenteral nutrition associated cholelithiasis is the major indication for cholecystectomy in the pediatric age group because of severe complication, but a number of recent studies report spontaneous resolution of the stones. We report a case of a female infant with cholelithiasis diagnosed by ultrasonogram at 88 days of age which is probably induced by prolonged lack of enteral feeding and TPN.
Adult ; Bile Acids and Salts ; Cholecystectomy ; Cholelithiasis* ; Enteral Nutrition* ; Enterohepatic Circulation ; Female ; Humans ; Infant ; Infant, Newborn ; Parenteral Nutrition ; Parenteral Nutrition, Total* ; Ultrasonography

PURPOSE: Neonatal jaundice is one of the most common problems in our country leading to hospitalization. Agar is low cost, low risk, and easily fed orally; it can bind bilirubin in the intestine, decreasing its enterohepatic circulation, thereby decreasing serum bilirubin levels. At present, however, the effectiveness of agar in the prevention and treament of neonatal jaundice is quite conflicting and controversy. Recently we have read Caglayan's 'Superiority of Oral Agar and Phototherapy Combination in the Treatment of Neonatal Hyperbilirubinemia'. The result was very hopeful and attractive enough, and which gave us a motivation to study if it was really of value. METHODS: From May 1995 to April 1996, a total 50 term neonates admitted in nursery of Dong-Eui Medical Center with the capillary serum bilirubin levels greater than 10mg/ dl were enrolled in the study. Those with pathologic causes and breast fed infants were all excluded. The neonates were randomly devided into two groups; 25 of conventional phototherapy alone (P group) and 25 of oral agar plus conventional phototherapy combination (A+P group). The study was terminated when the capillary serum bilirubins were decreased to 8mg/dl. Pastagar B (Pasteur Institute 64946) 500mg in 10ml distilled water were fed four times a day using 10ml syringes prior to bottle feeding. Capillary serum bilirubin levels were measured daily at 10:00 a.m. with heel pad samples. Daily stool frequency and adverse effects of treatment were observed closely. RESULTS: 1) The decrement of the serum bilirubin levels at first 24 hours of therapy was significantly different between P and A+P groups showing as 1.7+/-1.2 and 2.4+/-1.0mg/dl respectively (p<0.05). 2) Mean time for bilirubin to decrease to 8mg/dl was shorter in A+P group than in P group showing as 45.7+/-20.8 and 57.5+/-32.3 hours each other, but those differences were statistically insignificant (p>0.05). 3) No adverse effects such as rashes or abdominal pains were observed during treatment. Differences of mean stool frequency were significant between P and A+P groups showing as 3.7+/-1.2 and 4.7+/-2.0 times per day respectively (p<0.05). CONCLUSION: The agar plus conventional phototherapy combination was superior to conventional phototherapy alone at first 24 hours of therapy in neonatal hyperbilirubinemia, but further more careful researches would be necessary for using it routinely in the treatment of neonatal hyperbilirubinemia in future.
Abdominal Pain ; Agar* ; Bilirubin ; Bottle Feeding ; Breast ; Capillaries ; Enterohepatic Circulation ; Exanthema ; Heel ; Hope ; Hospitalization ; Humans ; Hyperbilirubinemia, Neonatal* ; Infant ; Infant, Newborn ; Intestines ; Jaundice, Neonatal ; Motivation ; Nurseries ; Phototherapy* ; Syringes ; Water

PURPOSE: Dioctahedral smectite is an alumina silicate of phyllitic structure and absorbs bile acid in the intestine, forming a non-absorbable complex preventing enterohepatic circulation. The purpose of this study is to clarify the value of dioctahedral smectite and the adequate dosage, in combination with phototherapy, as well as to confirm whether it shortens the duration of hospitalization and to compare dioctahedral smectite with cholestyramine. METHODS: Total 45 full-term neonate with a total bilirubin level greater than 12 mg/dl were studied. The neonate were randomly divided into three groups : 1) Only phototherapy group (A) 2) 3.0 g/day dioctahedral smectite with phototherapy group (B) 3) 1.0 g/kg/day cholestyramine with phototherapy group (C). RESULTS: The mean serum bilirubin level of group B and C decreased significantly compared to group A at 48, 72 and 96 hours after the beginning of the study. The duration of phototherapy and hospitalization significantly decreased in group B and C. CONCLUSION: The data revealed that oral administration of dioctahedral smectite not only increased the efficacy of phototherapy, but also shortened the duration of phototherapy and can substitute for cholestyramine.
Administration, Oral* ; Aluminum Oxide ; Bile ; Bilirubin ; Cholestyramine Resin* ; Enterohepatic Circulation ; Hospitalization ; Humans ; Hyperbilirubinemia, Neonatal* ; Infant, Newborn ; Intestines ; Jaundice, Neonatal ; Phototherapy* ; Silicates

AIMTo develop a pharmacokinetic model for the enterohepatic circulation of mycophenolic acid (MPA).

METHODSTwenty healthy volunteers were orally given a single dose of 500 mg mycophenolate mofetil. Plasma samples were collected during 48 hours and MPA concentration was measured by HPLC method. Pharmacokinetic (PK) model was established based on physiological and biopharmaceutical consideration and PK parameters were obtained using nonlinear mixed effect model.

RESULTSThe proposed model included an intestinal compartment and gall bladder compartment in addition to the central compartment. The predicted time-concentration curve and AUC0-t, Cmax, Tmax estimated by the established model were in agreement with the observations.

CONCLUSIONThe established model was well defined for the MPA disposition and could afford a useful approach for the further clinical investigation.

Adult ; Area Under Curve ; Enterohepatic Circulation ; physiology ; Glucuronides ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Male ; Models, Biological ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics

Even though there is a strong link between breast feeding and jaundice, it is natural and it may have a partially beneficial role in the neonate. There are two types of jaundice associated with breast feeding. First, insufficient caloric intake during the first week of life may increase serum unconjugated bilirubin concentration, which is known as "breast feeding jaundice (BFJ)". This increased severity of physiologic jaundice results from the increased enterohepatic circulation (EHC) of bilirubin, but not because of a factor in breast milk. Second, prolongation of unconjugated hyperbilirubinemia into the third and later weeks of life in the healthy newborn is a regularly occurring extension of physiologic jaundice, which is known as "breast milk jaundice (BMJ)". This is caused by a factor in breast milk inhibits the glucuronyl transferase in the liver and/or increases the EHC of bilirubin. The acceptable bilirubin level in the full-term healthy breast-fed infant needs to be discussed not only to prevent unnecessary interruption of breast feeding, but also to prevent kernicterus. Optimal breast feeding practices are crucial to prevent the BFJ and to minimize the intensity of BMJ. Further research is needed to clarify the benefit of bilirubin in relation to adaptation of extrauterine life.
Aluminum Hydroxide ; Bilirubin ; Breast ; Breast Feeding ; Carbonates ; Energy Intake ; Enterohepatic Circulation ; Humans ; Hyperbilirubinemia ; Infant ; Infant, Newborn ; Jaundice ; Kernicterus ; Liver ; Milk ; Milk, Human ; Transferases

OBJECTIVE: This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). METHODS: Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway. RESULTS: Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon. CONCLUSION Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.
Rats ; Animals ; Crohn Disease/pathology* ; Moxibustion/methods* ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Myeloid Differentiation Factor 88/metabolism* ; Colitis ; Inflammation ; Enterohepatic Circulation ; RNA, Messenger/metabolism*

The mucosa of the gastrointestinal (GI) tract exhibits hydrophobic, nonwettable properties that protect the underlying epithelium from gastric acid and other luminal toxins. These biophysical characteristics appear to be attributable to the presence of an extracellular lining of surfactant-like phospholipids on the luminal aspects of the mucus gel layer. Phosphatidylcholine (PC) represents the most abundant and surface-active form of gastric phospholipids. PC protected experimental rats from a number of ulcerogenic agents and/or conditions including nonsteroidal anti-inflammatory drugs (NSAIDs), which are chemically associated with PC. Moreover, preassociating a number of the NSAIDs with exogenous PC prevented a decrease in the hydrophobic characteristics of the mucus gel layer and protected rats against the injurious GI side effects of NSAIDs while enhancing and/or maintaining their therapeutic activity. Bile plays an important role in the ability of NSAIDs to induce small intestinal injury. NSAIDs are rapidly absorbed from the GI tract and, in many cases, undergo enterohepatic circulation. Thus, NSAIDs with extensive enterohepatic cycling are more toxic to the GI tract and are capable of attenuating the surface hydrophobic properties of the mucosa of the lower GI tract. Biliary PC plays an essential role in the detoxification of bile salt micelles. NSAIDs that are secreted into the bile injure the intestinal mucosa via their ability to chemically associate with PC, which forms toxic mixed micelles and limits the concentration of biliary PC available to interact with and detoxify bile salts. We have worked to develop a family of PC-associated NSAIDs that appear to have improved GI safety profiles with equivalent or better therapeutic efficacy in both rodent model systems and pilot clinical trials.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Bile ; Bile Acids and Salts ; Enterohepatic Circulation ; Epithelium ; Gastric Acid ; Gastrointestinal Tract ; Humans ; Intestinal Mucosa ; Lower Gastrointestinal Tract ; Mice ; Micelles ; Mucous Membrane ; Mucus ; Phenobarbital ; Phosphatidylcholines ; Phospholipids ; Rats ; Rodentia