Effects of high-lipase pancreatin on fecal fat, neutral sterol, bile acid, and short-chain fatty acid excretion in patients with pancreatic insufficiency resulting from chronic pancreatitis

Summary Conclusions Steatorrhea was almost completely stopped and malabsorption of neutral sterols and shortchain fatty acids was reduced by treatment of high-lipase pancreatin in Japanese patients with pancreatic insufficiency whose dietary fat consumption is low. Methods Fifteen patients with chronic pancreatitis complicated by steatorrhea who consumed an average of 48 g of dietary fats a day were selected as subjects and given 3 g of high-lipase pancreatin (lipase, 379,800 USP U/g), at each meal (total daily dose is 9 g) for a mean duration of 28.5 d. Fecal output and fecal fat neutral sterol, bile acid, and short-chain fatty acid excretion were determined before and after the course of pancreatin therapy. Results Pancreatin administration resulted in significant reductions (P<0.01) in fecal output (from 243.2 to 149.1 g), excretion of fecal fat, (from 12.3 to 3.9 g), animal sterols (from 816.3 to 604.6 mg), and shortchain fatty acids (from 52.6 to 18.5 mM). In contrast, no marked changes were recorded in fecal excretion of β-sitosterol (a plant sterol), bile acids, or the hydroxy fatty acid fraction. Fecal fat and short-chain fatty-acid excretion showed strong correlations with fecal output.     

Diet,fecal bile acids,and neutral sterols in carcinoma of the colon

Increased concentrations of fecal bile acids and neutral sterols or their degradation products have been linked to certain diets and are implicated in colonic carcinogenesis. We measured fecal bile acid and neutral sterol concentrations by thin-layer and gas-liquid chromatography in 15 patients with colonic adenocarcinoma, 23 controls, and 16 patients with nongastrointestinal cancer. We compared these results with dietary intake. Detailed dietary histories showed no differences among the groups in the ingestion of calories, protein, fiber, fat, or carbohydrate. A wide variation in fecal concentration of individual bile acids and neutral sterols was found within each group, but no significant differences in the total bile acid or total neutral sterol per gram dry weight feces were found. Decreased coprostanol, coprostanone, and lithocholic acid excretion was found in the colon cancer group compared with controls. The fecal excretion of all bile acids and neutral sterols was lower significantly in the nongastrointestinal cancer patients with liver metastases as compared with those without. We conclude that total bile acid and total neutral sterol excretion is similar in the three groups, all ingesting similar diets. We cannot confirm reported increased excretion of total bile acids nor excessive bacterial conversion to degradation products in colonic cancer patients. Hepatic metastases correlate with decreased fecal excretion of both bile acids and neutral sterols, which may be due to diminished hepatobiliary excretion.     

Effects of bran on serum cholesterol, faecal mass, fat, bile acids and neutral sterols, and biliary lipids in patients with diverticular disease of the colon

Twenty-two patients with symptomatic diverticular disease of the colon were randomly allocated to control and high-fibre groups so that the long-term effect (up to 12 months) of bran on serum, faecal and biliary lipids could be studied. Even in cases of high initial values, faecal mass was increased by bran and the change was positively correlated with the change in dietary fibre. Faecal fat and dry weight were also increased. Faecal bile acids were initially slightly raised and were positively correlated with wet weight both off and on bran. The latter significantly decreased the excretion and concentration of bile acids, in particular the high initial values. The change in bile acids was not correlated with the change in dietary fibre or faecal wet weight. Sterol balance values indicated that the bran-induced decrease in faecal bile acids was associated with a lower cholesterol synthesis. Serum cholesterol decreased significantly in two hypercholesterolaemic individuals only. Correlations between different parameters revealed that the higher the initial level or the greater the drop in cholesterol synthesis, the greater the decrease in serum cholesterol. Bran had no effect on the biliary saturation of cholesterol. The percentage of biliary deoxycholate was negatively correlated with faecal mass (less so with faecal bile acid output) both before and during bran and was significantly decreased by bran. The percentage of cholic acid increased correspondingly and that of chenodeoxycholate remained unchanged. Faecal bile acids also indicated that the synthesis of the two primary bile acids was lowered by bran to the same degree.     

Fecal bile acids,short-chain fatty acids,and bacteria after ileal pouch-anal anastomosis do not differ in patients with pouchitis

Construction of an ileal reservoir changes the fecal bacterial flora and the fecal composition of bile acids and short-chain fatty acids. We examined the relationships between pouch inflammation (pouchitis) and pouch content, as assessed by analysis of fecal bacteria, bile acids, and short chain fatty acids. Four groups were studied: ileal pouch-anal anastomosis (IPAA) for ulcerative colitis with pouchitis (N=10), IPAA without pouchitis (N=5), IPAA for familial adenomatous polyposis without pouchitis (N=5); and Brooke ileostomy for ulcerative colitis, which served as controls (N=5). Pouchitis was defined as ≥7 points on an 18-point pouchitis disease activity index. Aerobic and anaerobic bacteria were quantitatively cultured. Total aqueous-phase bile acids were measured by thin-layer chromatography and an enzymatic 3α-OH hydroxysteroid dehydrogenase method. Fecal short chain fatty acids were measured by gas liquid chromatography. All patients with an IPAA had higher ratios of anaerobes/aerobes and concentrations of anaerobic gram-negative rods than did patients with an ileostomy. There were no other differences between patient groups with respect to bacteria, aqueous-phase total bile acids, or fecal short-chain fatty acids. Fecal concentrations of bacteria, bile acids, and short-chain fatty acids were similar in patients with and without pouchitis, indicating that these factors can not be the sole cause of pouchitis.     

The colon in carbohydrate malabsorption: short-chain fatty acids, pH, and osmotic diarrhoea.

Short-chain (C2-C6) fatty acids (SCFA) are the major anions in colonic contents and the result of anaerobic fermentation of mainly saccharides. The effects and regulation of saccharide fermentation were studied in vitro and in vivo. In vitro faecal incubation was used to study the effects of lactose, glucose, and galactose and of pH on SCFA formation. Changing the pH to below 5 or above 11 abolished SCFA formation in the faecal incubates; in the pH 5-9 interval SCFA production was high, with only minor pH dependence. Adding glucose, galactose, or lactose to the incubation system increased SCFA production, but at high saccharide concentrations (100-300 mmol/l) SCFA formation was inhibited by the pH change. In vivo disaccharide malabsorption with increasing doses of lactulose caused a decrease in faecal pH to less than 5, values inhibitory to fermentation, before the appearance of carbohydrate in faeces. In 6 of 12 volunteers diarrhoea occurred suddenly and was caused by malabsorbed non-fermented carbohydrate. The six other volunteers had a gradual increase in faecal output with lactulose dose and developed diarrhoea before the appearance of saccharide in faeces. The intake of lactulose tolerated before diarrhoea ensued varied between individuals, with the majority having diarrhoea of more than 11/day at 160 g lactulose per day. At this dose SCFA absorption was estimated to be in the range 550 to 1150 mmol/day.     

Role of bile acids and neutral sterols in familial cancer syndromes of the colon

Cholesterol is quantitatively the most significant sterol in mammalian tissues. The major metabolic pathway of this sterol leads to the formation of bile acids. The structural similarities between carcinogenic aromatic hydrocarbons and bile acids aroused the suspicion that bile acids might play a role in carcinogenesis. In familial polyposis, a condition with a strong genetic predisposition to colonic cancer, a failure to degrade fecal cholesterol and bile acids to secondary products has been postulated as a marker of the phenotypic expression of this condition. In contrast, epidemiologic studies in populations at high risk for colonic cancer, and consuming diets rich in animal fat, protein, and refined carbohydrates, show a positive correlation with high fecal concentrations of bile acids and their metabolites. The suggestion that secondary bile acids might act in concert with colonic carcinogens in promoting neoplastic transformation is supported by observations from experimental studies. Among the secondary bile acids, lithocholic acid is unique in that it has been shown to be comutagenic, promote cell transformation, and induce DNA strand breakage,in vitro. It has also been shown to bind covalently to tissue proteins in human liver and in livers of carcinogen-treated rats.     

Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment.

Malabsorption of bile acids is known to occur in patients with pancreatic insufficiency particularly when due to cystic fibrosis. Abnormal biliary secretion or intraluminal acidic precipitation of bile acids could contribute to the steatorrhea of pancreatic insufficiency. To measure bile acid outputs and duodenal concentrations of bile salts and lipids simultaneously, we performed intestinal intubation and perfusion studies during feeding of a solid test meal in 6 healthy controls and 8 adult patients with advanced acquired exocrine pancreatic insufficiency. The effects of various treatment regimens were also investigated. Postprandial bile acid secretion was similar in all treatment groups. However, significant (P less than 0.05) reductions in micellar concentrations of bile acids and fatty acids were observed in untreated pancreatic insufficiency. These abnormalities were directly related to pH-induced precipitation of bile acids and were corrected only by the addition of cimetidine to standard pancreatin therapy. Thus, in pancreatic insufficiency, treatment with pancreatin plus cimetidine enhances fat digestion and absorption by reducing both acid-peptic inactivation of lipase and acidic precipitation of bile acids.     

Role of bacterial toxins,bile acids,and free fatty acids in colonic water malabsorption in tropical sprue

Colonic perfusion studies in 10 southern Indian patients with tropical sprue and nine matched healthy adults revealed a defect of water and sodium absorption from the colon in sprue. Heat-labile and heat-stable enterotoxin production was not detected in coliforms cultured from the feces of any of the 19 subjects. The 24-hr fecal bile acid output was increased in patients with sprue, but fecal aqueous bile acid concentrations remained within normal limits, and these did not correlate with defects in colonic water and sodium absorption. Fecal free fatty acid excretion was markedly increased in sprue. There was a negative correlation between fecal excretion of unsaturated free fatty acids and colonic water and sodium absorption.     

Cholesterol,non-cholesterol sterols and bile acids in paediatric gallstones

BackgroundDepending on underlying aetiopathogenetic factors human gallstones contain various amounts of cholesterol, non-cholesterol sterols and bile acids, which have remained unexplored in paediatric gallstone patients.AimsTo evaluate sterol and bile acids compositions of paediatric gallstones.Patients and methodsStudy group included 21 consecutively cholecystectomised children. Gas–liquid chromatography was used to quantitate gallstone sterols and bile acids. Results were compared to adult gallstones (n = 194).ResultsCholesterol stones (n = 9) had higher proportions of cholestenol and lathosterol, but lower those of lanosterol and phytosterols than pigment stones (n = 12) (p < 0.05 for each). Patients with gallstone cholesterol content over 70% were female. Gallstone cholesterol positively reflected body mass index and, in cholesterol stones-group, age (r = ∼+0.700, p < 0.05). Three patients on parenteral nutrition had brown pigment stones consisting of high amounts of campesterol and sitosterol ranging 483–9303 μg/100 mg of stone. Pigment stones had 13-fold higher amount of bile acids than cholesterol stones (p < 0.05). Black pigment stones contained ∼3-fold higher phytosterol proportions, and pigment stones and cholesterol stones had ∼43% lower proportions of deoxycholic acid than adults (p < 0.05).ConclusionGallstones in patients on parenteral nutrition are rich in phytosterols. With respect to gallstone sterols, gallstone disease of adolescent girls resembles that of adults. Composition of bile acids in paediatric gallstones is different from adults.     

Estimation of the 3-day faecal fat excretion and fat concentration as a differential test of malabsorption and maldigestion

The diagnostic efficiency of estimating the faecal fat excretion and faecal fat concentration in uncontrolled 3-day collections was estimated from a prospective series of 87 consecutive patients. The diagnoses were established on the basis of morphologic criteria, and the assimilation was established from the faecal 14C-triolein/3H-oleic acid test. These investigations showed the diagnostic sensitivity of the 3-day faecal fat excretion to be 90%. The 3-day mean faecal fat concentration was less than or equal to 5.1% w/w in patients with normal lipid assimilation. Of the patients with malassimilation 90% had a faecal fat concentration greater than or equal to 5.1% w/w. The faecal fat concentration was especially high in patients with maldigestion. When 10% w/w was used as the discrimination level between malabsorption and maldigestion, the faecal fat concentration correctly distinguished between these in 66% of the patients with malassimilation. The day-to-day variation of the faecal fat concentration was modest. Diagnosis of the lipid assimilation as estimated by the 1-day faecal fat concentration agreed with the diagnosis of the mean 3-day faecal fat concentration in 115 of the 122 1-day samples. The 1-day faecal fat concentration seems useful as a first screening test when malassimilation is suspected.     

非酒精性脂肪性肝病患者粪便短链脂肪酸含量测定的临床意义

目的 通过分析非酒精性脂肪性肝病(NAFLD)各疾病谱患者粪便短链脂肪酸(SCFA)含量及非酒精性脂肪性肝炎(NASH)高危患者治疗前后粪便SCFA含量的差异,初步探讨SCFA肠道代谢与NAFLD各疾病谱发生发展的关系。方法 选取2020年7月—2021年7月青海大学附属医院临床诊断为NAFLD的患者共90例,分为单纯性脂肪肝(NAFL)组(n=30)、NASH组(n=30)、非酒精性脂肪性肝纤维化组(n=30),选取同期健康体检者40例作为对照组,收集4组研究对象病例资料、粪便SCFA含量,以及NASH高危患者10例治疗干预3个月后临床指标和粪便SCFA含量。满足正态分布的计量资料多组间比较采用方差分析,组内比较采用配对样本t检验;不满足正态分布的计量资料采用Kruskal-Wallis H检验,组内比较采用配对样本的Wilcoxon符号秩和检验,相关性分析采用Spearman相关分析,诊断性评价采用ROC曲线分析。结果 非酒精性脂肪性肝纤维化组戊酸、己酸含量显著高于健康对照组,NAFL组戊酸、己酸含量显著低于健康对照组(P值均<0.05);非酒精性脂肪性肝纤维化组戊酸、己酸含...     

Exocrine pancreatic function and fat malabsorption in human immunodeficiency virus-infected patients.

BACKGROUND: Nutrients malabsorption frequently occurs in human immunodeficiency virus (HIV)-infected patients, but very few studies have investigated exocrine pancreatic digestive capacity in these patients. We therefore evaluated the frequency of exocrine pancreatic impairment and its eventual relation with fat malabsorption in HIV-infected patients. METHODS: Thirty-five HIV-infected patients (30 male, 5 female: mean age +/- standard deviation, 33.6 +/- 7.2 years) and 51 sex- and age-matched controls without gastroenterologic diseases were studied. In all subjects fecal elastase 1 (EL-1) was assayed, and fecal fat excretion was evaluated with the steatocrit test. RESULTS: Nineteen of 35 (54%) HIV-infected patients showed subnormal EL-1 values, whereas all the controls had normal values; furthermore, EL-1 values were significantly lower in patients than in controls: mean (95% confidence intervals), 207 ( 164-251 ) microg/g versus 312 (291-332) microg/g (P < 0.0001). Increased fecal fat excretion was observed in almost all (25 of 35) HIV-infected patients, and an inverse but not significant correlation was found between fecal EL-1 and steatocrit values. No association was found between reduced fecal EL-1 and the severity of HIV disease or nutritional and immunologic status. Opportunistic infections and drug administration had no influence on EL-1 concentrations in stools. CONCLUSIONS: Reduced exopancreatic function is frequent in HIV-infected patients but does not seem to be a major factor contributing to fat malabsorption.     

血清结合胆汁酸诊断脂肪肝

目的为脂肪肝患者实验室检查诊断提供有效的依据。方法采用反相高效液相色谱法（ＨＰＬＣ）检测３０例脂肪肝患者的血清７种结合胆汁酸，并以３０例无脂肪肝者作为对照。结果脂肪肝患者血清７种结合胆汁酸均高于无脂肪肝者（Ｐ＜０．０１）。结论血清结合胆汁酸有助于了解脂肪肝患者肝细胞病变程度，为早期诊治提供依据     

Analysis of faecal neutral sterols in patients with familial adenomatous polyposis by gas chromatography-mass spectrometry

Previous studies have suggested that patients with familial adenomatous polyposis (FAP) have increased faecal excretion of cholesterol but a reduction in cholesterol metabolites. It was consequently proposed that the degree of faecal cholesterol degradation could be used as a means of diagnosis. Developments in the extraction and analysis of faecal neutral sterols as well as the accurate means of diagnosing FAP by DNA analysis and indirect ophthalmoscopy has necessitated a re-examination of this proposal. Faecal neutral sterols were analysed in 10 patients with untreated FAP following a complete 5-day stool collection and compared with 9 healthy control subjects (including 4 siblings) closely matched for age and sex. The median [25 and 75, percentiles] stool wet weights were similar between the FAP (97.5 [69, 192] g · 24 h^-1) and the control (116 [61.5, 137] g · 24 h^-1) groups. Faecal cholesterol concentration was similar in the two groups (FAP=2.3 [1.4, 4.2]; control=3.5 [1.0, 6.0] mol · g^-1 dry wt) as was the concentration of total neutral sterols not including plant sterols (FAP=17.2 [13.4, 21.0]; control=18.2 [7.4, 21.6] mol · g^-1 dry wt). There were no significant differences in the proportions of cholesterol metabolised between the FAP (82.3 [74.2, 93.5]%) and control (72.1 [5.7, 81.3]%) groups. This study does not support the notion that faecal neutral sterol metabolism is uniquely different in patients with FAP.

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Résumé Des études précedentes avaient suggéré que les malades avec polypose adénomateuse familiale (PAF) avaient une excrétion fécale augmentée de choléstérol mais une réduction des métabolìtes du choléstérol. On a donc proposé que les degrés de dégradation fécale du choléstérol puisse être utilisée comme moyen de diagnostic. Le développement dans l'extraction et l'analyse des stérols neutres fécaux aussi bien que des moyens appropriés de diagnostiquer la PAF par analyse du DNA et ophthalmoscopie indirecte a nécessité un ré-examen de cette proposition. Les stérols neutres fécaux, ont été analysés chez 10 patients avec une PAF non traitée après une collection complète des matières de 5 jours et comparés avec 9 sujets contrôles sains (comprenant 4 enfants de mêmes parents) étroitement appareillés pour l'âge et le sexe. Les poids moyens (25 et 75 percentiles) de selles humides étaient similaires chez les PAF (97.5 (69, 192) g · 24 h^-1) et les contrôles (116 (61.5, 137) g · 24 h^-1). La concentration de choléstérol fecal était similaire dans les deux groupes (PAF=2.3 (1.4, 4.2); controle=3.5 (1.0, 6.0) mol · g poids sec) de même que la concentration de stérols neutres totaux stéroïdes végétaux exclus (PAF=17.2 (13.4, 21.0); controle 18.2 (7.4, 21.6) mol · g poids sec). Il n'y avait pas de différence significative dans les proportions de choléstérol métabolisé entre les PAF (82.3 (74.2, 93.5)%) et les contrôles (72.1 (5.7, 81.3)%). Cette étude ne confirme pas la notion que le métabolisme des stérols neutres fécaux est uniquement différent chez les patients avec une PAF.

     

短链脂肪酸在肠道中的生理作用

越来越多的证据显示,短链脂肪酸对肠道的能量供应、肠黏膜屏障的维持、肠道高敏感和肠道动力的调节、免疫调节及抗肿瘤效应等有重要作用。进一步明确短链脂肪酸的生理作用及其与肠道相关疾病的关联及其内在机制,对肠道疾病的预防与治疗有重要意义。该文就短链脂肪酸在肠道中的生理作用作一综述。     

Ratio of primary and secondary bile acids in feces

PURPOSE: Increases in fecal bile acids may play a role in colorectal carcinogenesis. The authors tested the hypothesis that high concentrations of primary and secondary bile acids are more common in patients with colon cancer than in patients with other gastrointestinal diseases. METHODS: In this retrospective study the secondary bile acid deoxycholic acid and the primary bile acid cholic acid were measured in the feces by enzyme-linked immunoabsorbent assay in 63 patients with colorectal cancer, 24 patients with gastric cancer, 11 patients with biliary disorders, and 47 healthy volunteers. RESULTS: Preoperatively, the mean deoxycholic acid values tended to be higher and the cholic acid values were significantly lower in patients with colorectal cancer than in healthy subjects. Patients with other gastrointestinal diseases had lower deoxycholic acid and cholic acid values than healthy subjects. In healthy subjects the deoxycholic acid to cholic acid ratio ranged from 0.10 to 2.86 (mean, 0.88), but in almost two-thirds, the ratio did not exceed 1. In contrast, the mean preoperative ratio in patients with colorectal cancer was 2.26 (range, 0.06-7.17; P < 0.0001) and tended to be higher in patients with advanced cancer and in those with sigmoid and rectal tumors. If 1.1 is taken as the upper limit of normal for deoxycholic acid to cholic acid ratio, 67 percent of patients with colorectal cancer had an abnormal value preoperatively. CONCLUSION: A high deoxycholic acid concentration and deoxycholic acid to cholic acid ratio may be indicators of colorectal cancer. Further study is needed to improve sensitivity and specificity, perhaps by combining fecal bile acid measurements with other tests, and a large prospective trial may be warranted to determine whether these measurements have value in screening for this common cancer.     

Hypersecretion of biliary fatty acids in patients with exocrine pancreatic disease

Summary The fatty acid composition of bile secreted into the duodenum in the first 10 min after an intravenous (i.v.) injection of Boots secretin (2 CHRu kg^-1) has been analysed by gas liquid chromatography in 11 healthy volunteers, 8 patients without pancreatic disease, 27 patients with exocrine pancreatic disease who had not altered their diet substantially (acute pancreatitis 8; chronic pancreatitis 16; cancer 3) and 11 patients with exocrine pancreatic disease on low fat intakes (40 g/day) for at least 6 months. The mean values for total fatty acid outputs (after back transformation of the logged data) were significantly higher in each subgroup of patients with pancreatic disease on their usual diets (acute 134, chronic 189, cancer 235 mg) than in the two subgroups of controls (30 and 55 mg), due to significant increases in the outputs of every fatty acid, C16:0 through to C22:5. This finding, which was usually not apparent in patients with pancreatic disease on low-fat diets, may reflect the combined influence of dietary fat intakes and hepatic enzyme induction. Comparison of the fatty acid outputs in endoscopically collected bile and duodenal juice after separate injections of secretin three hours apart indicate that: (a) analysis of duodenal juice within 10 min of stimulation by Boots secretin provides valuable information on the composition of hepatic bile; (b) the increased phospholipid output in the untreated patients is due to hypersecretion and does not merely represent a ‘washout’ phenomenon.