PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “secondary bile acids”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Toxoplasma gondii infection disrupts secondary bile acid transformation in feline gut microbiota.

UNLABELLED: Bile acid (BA) transformation relies on gut microbiota and is vulnerable to Toxoplasma gondii infection, yet feline microbial BA-transforming capacity upon toxoplasmosis remains unclear. Here, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. The results revealed that the feline gut microbiome harbored widespread genetic potential for BA transformation but lacked a complete 7α-dehydroxylation pathway due to the absence of the key gene baiE. The BA transformation-related genomes (2,045 in total) were predominantly from the phyla Bacillota_A and Actinomycetota, among which only 37 encoded baiB, all belonging to Bacillota_A. The distribution of BA transformation-related genes varied across intestinal regions: genes encoding 7α-HSDH were primarily enriched in the small intestine, whereas genes encoding 3α-HSDH, baiCD, and baiH were more abundant in the large intestine. Additionally, the abundance of genes encoding BSH and 3α-HSDH increased significantly in the small intestine on day 3 post-infection, accompanied by increases in the phylum Bacillota_C and genera such as Blautia_A, Enterococcus_E, and Ligilactobacillus. Serum metabolomics revealed a significant increase in cholesterol levels post-infection, supporting the impact of T. gondii infection on intestinal BA transformation. These findings illustrated that the feline gut microbiota played an important role in BA transformation and that T. gondii infection disrupted the microbial potential for secondary BA transformation. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis. IMPORTANCE: Bile acid (BA) transformation plays a critical role in host metabolism and immune regulation. Although studies on BA transformation are increasing, the capacity for BA transformation within the feline gut microbiota and the impact of Toxoplasma gondii infection on this capacity remain unclear. To bridge this gap, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. Our findings revealed that the feline gut microbiome lacked a complete 7α-dehydroxylation pathway, and the specific functions involved in BA transformation may differ between the small and large intestines. Furthermore, integrated metagenomic and serum metabolomic analyses suggested that T. gondii infection disrupted BA transformation capacity in the small intestine. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis.

Toxoplasma gondii↗
PubMed1978

Effect of bile acids and dietary fat on large bowel carcinogenesis in animal models.

Epidemiologic and laboratory studies suggest that dietary fk actors, particularly high intake of fat and animal protein, and high concentration of bile acids and neutral sterols of the large bowel lumen are strongly associated with large bowel carcinogenesis. Such concepts guided our studies on animal models. Rats fed diets high in fat and/or protein had a higher incidence of DMH-induced large bowel tumors than rats fed standard diets. The source of fat and protein, animal vs. vegetable, had no major influence. High fat intake was associated with an increased excretion of fecal bile acids, particularly secondary bile acids, and neutral sterols. The repeated intrarectal doses of lithocholic acid or deoxycholic acid enhanced the development of MNNG-induced large bowel tumors in rats. Colostomized rats treated with intrarectal dose of MNNG had no tumors in the excluded segment. It suggests that luminal contents play a significant role in the induction of large bowel cancer. The results show that higher levels of bile acids in the large bowel lumen, resulting from high fat intake, exert a promoting effect on the development of large bowel cancer.

Animals↗
PubMed1977

Bile acids, diarrhea, and antibiotics: data, speculation, and a unifying hypothesis.

The primary bile acid, chenodeoxycholic acid, and the secondary bile acid, deoxycholic acid, when present at a concentration of greater than 3 mM, induce salt and water secretion from the human colon and cause a marked increase in the permeability of the human colon to molecules of a molecular weight of 200-500 daltons. Scanning electron microscopy indicates that this action may be associated with tissue damage in some species. In the healthy individual, the primary bile acids, cholic and chenodeoxycholic acid, are dehydroxylated in the colon and are simultaneously precipitated from solution; at pH less than 7, deoxycholic and lithocholic acid are insoluble. In patients with bile acid diarrhea resulting from bile acid malabsorption, dehydroxylation is decreased, and the concentration of bile acids in the colon is markedly elevated. The major secretory bile acid in solution is chenodeoxycholic acid. Administration of cholestyramine, a resin that binds bile acid, reduces the elevated concentration of chenodeoxycholic acid and abolishes the diarrhea. These facts can be used to develop a unifying hypothesis which proposes that elevated concentrations of primary bile acids in the colon play a role in diarrhea and pseudomembranous colitis induced by clindamycin.

Anti-Bacterial Agents↗
PubMed1979

[Bile acids. I. Nature, physiology, and functions (author's transl)].

Bile acids play a fundamental role in the degradation and absorption of intestinal lipids. The primary ones are cholic acid and chenodeoxycholic acid which are synthesized from cholesterol in the liver and conjugate with taurine and glycine amino acids. The secondary bile acids are derived from the primary ones by the enzyme action of intestinal bacteria through a process of deconjugation and dehydroxylation. Their detergent property is based on the molecular configuration of these compounds, which present a hydrophilic and a hydrotion of these compounds, which present a hydrophilic and a hydrophobic surface. The different enzymes in the liver cells that intervene in the process of synthesis of bile acids are now known. A basic element in their physiology is the enterohepatic circulation, enabling the organism to take maximum advantage of these compounds. The dynamics of the cycle are maintained and regulated by the system of uptake and secretion of the cells, cholecystokinin, intestinal peristalsis, active transport across the ileal membrane, and by portal venous flow. Much of our knowledge about the biogenesis and functions of the bile acids has been acquired quite recently. Research over the past three decades has contributed to a great advance in our understanding of their physiology.

Bile Acids and Salts↗
PubMed1978

Bile acids of a 3200-year-old Egyptian mummy.

The bile acids of the gall bladder and hepatic tissue of a 3200-year-old Egyptian mummy were isolated by thin-layer chromatography and identified by combined gas-liquid chromatrography and mass spectrometry. Except for complete deconjugation and extensive dehydration, the bile acids were found to correspond in their qualitative and quantitative composition to the gall bladder bile acids of modern man. The secondary bile acids constituted about 50% of the total and were identified as the normal bacterial oxidoreduction products of the primary bile acids and their dehydration products. In addition a series of unsaturated bile acids were identified, which corresponded to the dehydration products of cholic and chenodeoxycholic acids. It is suggested that both bile acid deconjugation and the limited oxidoreduction were probably brought about by the Clostridium organisms identified in the tissue. On the basis of the bile acid composition it is concluded that the ancient man metabolized cholesterol along the same pathways as modern man.

Bile Acids and Salts↗
PubMed1977

[Enterohepatic circulation of bile acids and biliary lipid secretion].

The enterohepatic circulation of bile acids in man is reviewed. The chemistry of biliary bile acids is summarized and related to the formation of primary bile acids in the liver and secondary bile acids in the intestinal lumen. New findings showing that lithocholic acid is absorbed in man are presented, and the recent experiments showing that lithocholic acid is extensively sulfated are reviewed. The consistent hepatotoxicity of chenodeoxycholic acid in the rhesus monkey, which contrasts with its non-toxicity in man, is explained by the inability of the rhesus monkey to sulfate abosrbed lithocholic acid; this accumulates in the enterohepatic circulation of the monkey causing liver damage. In man, absorbed lithocholic acid is rapidly sulfated, and the sulfated conjugates are excreted fecally without enterohepatic cycling. The physical chemistry of bile is highlighted, and it is shown that the saturation of bile with cholesterol depends on the amount of bile acids passing through the liver: at low bile acid flow rates, such as occurs during overnight fasting, bile is supersaturated in both gallstone and healthy persons. Chenodeoxycholic acid decreases cholesterol secretion into bile, renders bile unsaturated during most of the day and night, and thus induces gallstone dissolution.

Animals↗
PubMed1977

Evidence for renal control of urinary excretion of bile acids and bile acid sulphates in the cholestatic syndrome.

1. The bile acids and bile acid sulphates in the urine, serum and bile of eight cholestatic patients were studied quantitatively by gasliquid chromatography and gas-liquid chromoatography/mass spectrometry. 2. The primary bile acids (cholic acid and chenodeoxycholic acid) comprised on average 94% of the total bile acids in bile, 70% in the serum and 64% in urine. 3. The percentage composition of bile acids in bile was relatively constant and was not influenced by the degree of cholestasis. In contrast, in the serum only the primary bile acids were increased, the concentrations of the secondary bile acids (deoxycholic acid and lithocholic acid) and the minor bile acids remaining constant. 4. The data do not support the hypothesis that monohydroxy bile acids accumulate in cholestasis and are related to the pathogenesis of this syndrome. 5. The pattern of bile acid urinary excretion was similar to that in the serum. But in one patient, 3alpha, 7beta, 12alpha-trihydroxy-5beta-cholan-24-oic acid was a principal urinary bile acid, although very low concentrations of the compound were found in that patient's serum, suggesting that some of the minor bile acids in urine may originate by epimerization in the kidney. 6. In bile only a small proportion of the bile acids was sulphated (range 2.1-4.6%) and in serum the degree of sulphation was very variable (9-50%). However, in urine, sulphate esters accounted for a large proportion of the total bile acids (33-72%). 7. The output of bile acid sulphate in the urine was related to the urine total bile acid output but the serum concentration of bile acid sulphate remained relatively constant. Consequently, in contrast to the non-sulphated bile acids, whose renal clearance was relatively constant, the renal clearance of sulphated bile acids was directly related to the urine total bile acid output. This finding is inconsistent with the earlier hypothesis that their predominance in urine was due to a high renal clearance. It may indicate renal synthesis of some of the bile acid sulphates in the urine and/or inhibition of active renal tubular reabsorption of sulphated bile acids by non-sulphated bile acids.

Adult↗
PubMed1977

Bile acid metabolism in ileostomy patients.

In ten ileostomy patients, a 14C-cholylglycine breath test was performed. The 14CO2 in the exhaled air and the 14C bile acid quantity and composition and fat content in the subsequent 24 h ileostomy effluent were determined and compared to the values in twenty healthy controls. The results show that in ileostomy patients only minor bile acid-deconjugation occurs in vivo. Deconjugation in the ileostomy bags was found to be mainly responsible for the absence of conjugated bile acids in many of the ileostomy effluent samples. Secondary bile acids were not present in these patients, as determined by TLC. The fecal fat and bile acid excretion was found to be in the normal range in ileostomy patients provided no concomitant ileum resection was present.

Bile Acids and Salts↗
PubMed1979

The pancreatic duct mucosal barrier.

The main pancreatic duct in cats possesses a relatively strong barrier to the diffusion of bicarbonate ions (HCO3-). We studied some of the characteristics of this barrier by perfusing the duct with a solution similar in composition to pancreatic juice before and after exposing the duct mucosa to various test agents. The difference in net flux of HCO3- across the duct before and after exposure to the test agent reflected damage to the barrier. The barrier was damaged by infected bile, aspirin (pH 2.3), hydrochloric acid (pH 2.3), ethanol (5 to 10 per cent), and secondary bile acids. It was not damged by sterile bile, aspirin (pH 6.5), and primary bile acids. These data indicate that the barrier to back diffusion in the pancreatic duct has unique properties, different in some respects from the properties of the gastric mucosal barrier. Furthermore, the barrier is vulnerable to some agents thought possibly to have a role in the pathogenesis of pancreatitis and pancreatic cancer.

Animals↗
PubMed1979

Urinary bile acids in late pregnancy and in recurrent cholestasis of pregnancy.

The metabolic profiles of urinary bile acids in pregnant women in the last trimester and patients with recurrent intrahepatic cholestasis of pregnancy (RCP) were studied. Following separation according to mode of conjugation, about thirty different bile acids were quantitatively analysed by gas chromatography-mass spectrometry. In all patients the sulphate fraction comprised 50--90% of the total bile acids. In RCP a shift from glycine to taurine conjugation was noted to together with a slight relative increase in sulphation. A ten- to hundred-fold increase in cholic and chenodeoxycholic acids was seen in RCP, the increase being mainly in the sulphate fraction. Tetrahydroxylated bile acids, tentatively regarded as 1- and 6-hydroxylated products of cholic acid, were quantitatively important in patients with RCP. The relative amounts of the secondary bile acids, deoxycholic and lithocholic acids, decreased with increasing cholestasis. Metabolites hydroxylated at C-6 were common, and the excretion of hydroxylated at C-6 were common, and the excretion of hyocholic acid was positively correlated to that of chenodeoxycholic acid. An increase in the excretion of 5 alpha-configurated bile acids in RCP was noted. A positive correlation between the excretion of 3 beta-hydroxy-5-cholenoic acid and 3 beta,12 alpha-dihydroxy-5-cholenoic acid indicates a metabolic relationship between the two compounds. Because of the relatively small amounts of lithocholic and 3 beta-hydroxy-5-cholenoic acids in patients with RCP, these compounds do not seem to be of pathogenetic importance in this type of cholestasis.

Bile Acids and Salts↗
PubMed1979

Bile acid, neutral sterol and faecal fat excretion in subjects treated with fenfluramine and its relationship to fenfluramine-induced diarrhoea.

Bile acid, neutral sterol and faecal fat excretion was studied over a period of 9 weeks in a group of 16 healthy subjects before, during and after administration of fenfluramine. Statistical analysis revealed a significant increase in bile acid excretion during the drug phase (P less than 0.02); and during recovery period of 3 weeks (P less than 0.05). Faecal neutral sterol, as the total of coprostanol and cholesterol elimination was also enhanced after fenfluramine. Coprostanol was replaced by cholesterol in 12 subjects. Faecal fat was studied in 6 subjects, the excretion increased during the drug phase (P less than 0.05), and remained elevated during the post-drug period (P less than 0.01). The composition of the bile acids remained unaltered in all the subjects except 3 who had a fenfluramine-induced watery diarrhoea; and these excreted chenodeoxy and cholic together with smaller amounts of secondary bile acids. A higher excretion of bile acids was found in the 8 overweight subjects (P less than 0.01) before ministration of fenfluramine. These results are discussed in an attempt to correlate the effect of fenfluramine with changes in bile acid and neutral sterol excretion, and its relationship to fenfluramine-induced diarrhoea.

Bile Acids and Salts↗
PubMed2026

Gut microbiota dynamics and metabolic pathways associated with bleomycin-induced pulmonary fibrosis progression.

BACKGROUND: Pulmonary fibrosis (PF) is a progressive respiratory disease characterized by epithelial injury, aberrant repair and excessive extracellular matrix deposition. Although the gut-lung axis is increasingly implicated in respiratory disorders, stage-resolved characterization of gut microbiota taxonomic and functional potential during PF development is limited. METHODS: We established a bleomycin-induced murine PF model and performed cross-sectional shotgun metagenomic sequencing of fecal samples from separate cohorts at three defined stages: baseline (control), day 7 (early fibrosis; M7), and day 14 (established fibrosis; M14). Microbial taxonomy, alpha/beta diversity, and predicted functional capacity were inferred using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active enZymes (CAZy) annotations; associations were assessed using Procrustes and Spearman correlation analyses. RESULTS: Histopathology and immunohistochemistry confirmed progressive fibrogenesis with increased TGF-β1 and α-SMA expression. Compared with baseline, bleomycin-treated groups exhibited stage-specific shifts in gut microbial composition, including depletion of mucin-associated taxa (e.g., Prevotella, Akkermansia muciniphila) and expansion of Muribaculaceae- and Clostridiaceae-affiliated taxa. Alpha and beta diversity metrics differed across groups. KEGG/CAZy-based annotations revealed predicted, stage-dependent changes in microbial metabolic potential, including early reductions in pathways related to amino acid and glycan metabolism (M7) and later increases in predicted starch/sucrose catabolism, phosphotransferase system (PTS) representation, and secondary bile acid biosynthesis (M14). Correlation analyses linked compositional shifts to these predicted functional changes. CONCLUSION: In a stage-resolved, cross-sectional study, bleomycin-associated pulmonary fibrosis was accompanied by compositional and predicted functional alterations in the gut microbiota. These data identify candidate taxa and predicted pathways for follow-up mechanistic testing, but functional (metabolomic) and causality experiments are required to confirm whether and how microbial changes contribute to PF pathogenesis.

Animals↗
PubMed1979

[Clinical significance of serum bile acid radioimmunoassay in hepatobiliary diseases--with special reference to the CG/SLCG ratio (author's transl)].

Both serum cholylglycine (CG) and sulfolithocholylglycine (SLCG) levels were radioimmunoassayed by PEG method in 209 samples (204 hepatobiliary diseases, 5 normal controls). 1) The results revealed that serum bile acid levels were excellent indicators for hepatic dysfunction in comparison with the conventional liver function tests. 2) Means of 19.4 +/- 9.3 microgram/dl for CG and 21.7 +/- 6.7 microgram/dl for SLCG were obtained in controls. Most hepatobiliary diseases demonstrated abnormally high bile acid levels, with extremely high CG values in conditions with bile stasis. 3) To differentiate various hepatobiliary diseases more clearly, the ratio of the primary and secondary bile acids (CG/SLCG ratio) was introduced (1.0 +/- 0.6 for controls). In cases of bile stasis, CG/SLCG ratios ranged from 7.8 +/- 4.8 for intrahepatic cholestasis to 34.8 +/- 27.6 for congenital biliary atresia, while other hepatic disorders demonstrated relatively low values. We conclude that the CG/SLCG ratio is a useful index for cholestasis. Diagnosis of the congenital biliary atresia could be possible.

Biliary Tract Diseases↗
PubMed1979

Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon.

An in vivo intestinal perfusion system was used to study the effects of different bile acids on fluid secretion, mucosal permeability, and mucosal morphology in the rabbit colon. To define the structure-activity relationships of the bile acids, nine unconjugated bile acids were used, varying only in the number (two or three) or position (3, 7, or 12 or various combinations) of hydroxy or keto nuclear substituents. Results showed that bile acids with two hydroxy groups in the alpha configuration at the 3,7 position, 3,12 position, or 7,12 position induced fluid secretion, increased mucosal permeability, and produced mucosal damage as assessed by light and scanning electron microscopy and quantitated by DNA loss during perfusion. Replacement of hydroxy groups by keto groups or a change from alpha to beta configuration for the hydroxylic substituent in the 7 position abolished all three activities. Trisubstituted derivatives, whether hydroxy or keto, did not affect fluid secretion permeability or cause mucosal damage. These studies indicate that of the major primary and secondary bile acids in man, only deoxycholic and chenodeoxycholic acids alter colonic structure and function in the rabbit. They show further that the cathartic effects of bile acids have specific structural requirements; and they show that bile acid-induced secretion was invariably associated with increased mucosal permeability and epitheliolysis.

Animals↗
PubMed1978

Bile acid composition in patients with and without symptoms of postoperative refulx gastritis.

Reflux of bile into the stomach is common after surgery for duodenal ulcer disease; however, only a minority of patients may develop significant gastritis and pain. Gastric aspirates from two groups of patients after operation for duodenal ulcer were quantitatively and qualitatively analyzed. Group A patients were asymptomatic and the bile composition was normal. Group B patients were symptomatic and had a significant increase in the secondary bile acid, deoxycholic acid. The concentration of bile acid was similar in the two groups. This alteration in bile acid composition, with an increase in deoxycholic acid, may be an important factor in determining which patients with bile reflux develop gastritis.

Bile↗
PubMed1978

Bile acid conjugation in the chimpanzee: effective sulfation of lithocholic acid.

To characterize the hepatic biotransformation in the chimpanzee of the primary bile acid chenodeoxycholic acid (chenic) and its major bacterial metabolite lithocholic acid (lithocholic) a mixture of trace amounts of 14C-lithocholic and 3H-chenic was injected intravenously into two animals with a bile fistula; the chemical form of radioactivity appearing in bile was inferred using thin layer chromatography. About 80% of chenic, and 70% of lithocholic was recovered in 90 min. Chenic was completely conjugated in bile, appearing predominantly as chenyltaurine (52%) and chenylglycine (37%). An unidentified conjugate (about 11%) was also found. Lithocholic was excreted completely as taurine and glycine conjugates, but the majority (63%) of conjugates was sulfated. Sulfation increased progressively with time, and lithocholylglycine was sulfated more than lithocholyltaurine. We conclude that the chimpanzee is similar to man in that the secondary bile acid lithocholic is efficiently sulfated. The chimpanzee thus differs from the baboon and rhesus monkey which sulfate lithocholic poorly. However, the chimpanzee differs from man and is similar to the baboon and rhesus monkey in showing preferential conjugation of bile acids with taurine. The results imply that hepatotoxicity caused by chenic, which is well documented in the rhesus monkey and baboon and has been related to defective lithocholic sulfation, should not occur in the chimpanzee.

Animals↗
PubMed1977

Resistance of germfree rats to indomethacin-induced intestinal lesions.

Indomethacin given orally to conventional rats produced in three days a syndrome, often fatal, of intestinal lesions characterized by multiple ulcers and peritonitis. Male germfree rats were found to be resistant to this effect of indomethacin, while female germfree rats developed very mild lesions. Germfree rats became sensitive again to such lesions when monocontaminated with E. coli. In such animals, however, the lesions were less severe than in conventional animals, presumably because more than one microorganism is necessary for the full syndrome to develop. These results suggest that microorganisms are necessary for the development of indomethacin-induced intestinal lesions. Secondary bile acids, absent in germfree animals, may also be necessary. The prostaglandin deficiency caused by indomethacin appears to weaken the resistance of the intestinal mucosa to microorganisms and/or their toxins. The latter may then penetrate the mucosa, damage the cells and produce ulcers and perforations. Since several prostaglandins also protect against indomethacin-induced lesions, the hypothesis is advanced that certain prostaglandins may protect the mucosa ("cytoprotection") by preventing the spread of microorganisms and/or their toxin through the intestinal wall.

Animals↗