scholarly journals INTESTINAL MECHANISMS OF ENTEROHEPATIC CIRCULATION DISTURBANCE OF BILE ACIDS IN CHOLELITHIASIS

2017 ◽  
Vol 72 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Ya. M. Vakhrushev ◽  
A. P. Lukashevich ◽  
A. Yu. Gorbunov ◽  
I. A. Penkina
Keyword(s):  
Small Intestine ◽  
Bile Acids ◽  
Large Intestine ◽  
Intestinal Microbiota ◽  
Enterohepatic Circulation ◽  
Controlled Trial ◽  
Bacterial Overgrowth ◽  
Control Group ◽  
Hydrogen Breath Test ◽  
Biochemical Examination

Background: Cholelithiasis is one of the most common diseases of the digestive system which affects all segments of the population and preserves a stable growth of incidence rates. In recent years the development of cholelithiasis is associated with impaired enterohepatic circulation (EHC) of bile acids (BA). The small intestine (SI) plays an important part in EHC of BA because 80‒90% of BA are absorbed into the blood after deconjugation by bacteria in the SI. However, in spite of a number of works dealing with the problem of EHC of BA at the intestinal level, the problem is far from being solved. Aims: To assess the association between the level of bile acids in the blood and bile of patients with cholelithiasis and disturbance of resorbing function of the small intestine as well as changes in the condition of the intestinal microbiota. Materials and methods: Non-randomized controlled trial. The study group included patients aged 18‒74 with lithogenic stage of cholelithiasis. The diagnosis was based on clinical data and the results of ultrasound examination of the gallbladder. Bile acids in the blood and bile were determined by mass spectrometry using the apparatus AmazonX (Bruker Daltonik GmbH, Bremen, Germany). Biochemical examination of bile was conducted. Absorption in the small intestine was studied by functional glucose tolerance test. Condition of the intestinal microbiota was assessed by the hydrogen breath test with lactulose using the apparatus LaktofaH2 (AMA, St. Petersburg). Stool culture was performed in selective media. Results: 115 patients aged 18 to 74 with prestone stage of cholelithiasis and 25 healthy people, comparable in age and sex, were examined. In patients with prestone stage of cholelithiasis biochemical examination of bile revealed increased cholesterol and decreased bile acids and bile acids-cholesterol ratio in B and C bile. The level of bile acids in the blood was reduced in comparison with the control group; it was associated in particular with a significant reduction in chenodeoxycholic, deoxycholic and glycodeoxycholic acids. Resorption in the small intestine was increased in patients with cholelithiasis compared with the control group (blood glucose increase within 30 minutes after the glucose load was 3.13±0.17 and 2.32±0.11 mmol/l respectively; p0.05). In the majority of patients small intestinal bacterial overgrowth (SIBO), mainly (75% of patients) associated with ileocecal insufficiency, and dysbiosis in the large intestine were established (88 and 100% of patients respectively). Conclusions: The small intestine is an important component in disturbance of enterohepatic circulation of bile acids. Significant changes in deconjugation of bile acids occur due to SIBO in the distal ileum and dysbiosis in the large intestine, thus disturbings the proportion of fractions of bile acids in the blood and bile.

scholarly journals ASSOCIATION OF INTESTINAL BACTERIAL OVERGROWTH AND DISEASES OF HEPATOBIARY TRACT

2019 ◽  
Vol 9 (1) ◽  
pp. 64-69
Author(s):  
Ya. M. Vakhrushev ◽  
A. P. Lukashevich ◽  
E. V. Suchkova
Keyword(s):  
Total Cholesterol ◽  
Bile Acids ◽  
Bacterial Overgrowth ◽  
Control Group ◽  
Hydrogen Breath Test ◽  
Alcoholic Fatty Liver ◽  
Overgrowth Syndrome ◽  
Intestinal Bacterial Overgrowth ◽  
Hepatobiliary System ◽  
Intestinal Dysbiosis

The aim. Find out the nature of the changes of the hepatobiliary system in patients with intestinal bacterial overgrowth and study the possible mechanisms of their association.Materials and methods. 148 patients with intestinal bacterial overgrowth and intestinal dysbiosis were examined. The level of total cholesterol, cholestasis and cytolysis markers was determined in the blood using the analyzer «Labsystems» (Finland). Intestinal bacterial overgrowth syndrome was assessed using a hydrogen breath test with lactulose on the LactophaH2 apparatus of AMA (St. Petersburg). Intestinal dysbiosis was determined by plating feces on nutrient media. Bile acids in bile were determined on the AmazonX mass spectrometer (Bruker Daltonik GmbH, Bremen, Germany). Ultrasound examination of the abdominal cavity performed with the apparatus «SHIMADZU SDN-500» (Japan). Liver elastography was performed using the AIXPLORER apparatus (France).Results. The syndrome of intestinal bacterial overgrowth in 67% of cases was established in the presence of ileocecal insufficiency, in 33% of cases — with preserved ileocecal function. The combination of intestinal bacterial overgrowth syndrome and intestinal dysbiosis was detected in 81,8% of patients. The majority of the examined patients showed clinical symptoms of damage the hepatobiliary system and intestines, which was confirmed by change laboratory parameters — increase the level of total cholesterol, markers of cholestasis and cytolysis compared with the control group. In the study of bile acids in bile, decrease free (mainlycholic) and increase conjugated (glycodesoxycholic, taurodesoxycholic, glycocholic, taurocholic) bile acids was observed compared with the control group. In general, patients with the syndrome of intestinal bacterial overgrowth revealed the presence of non-calculous cholecystitis — in 11,5% of cases, I stage of cholelithiasis — in 25,7%, II stage of cholelithiasis — in 18,9%, non-alcoholic fatty liver disease on stage steatosis and steatohepatitis — in 43,9% of cases.Conclusion. Intestinal bacterial overgrowth syndrome is the beginning of bacterial translocation, which is the triggering factor in inflammation of the liver and biliary tract. In turn, diseases of the hepatobiliary system contribute to the development of intestinal dysbiosis by reducing the synthesis of bile acids with antibacterial action, as well as violations of their excretion. Thus, strong association of intestinal bacterial overgrowth syndrome with damage to the hepatobiliary system has been established.

scholarly journals The Nonsteroidal Anti-Inflammatory Drug Ketorolac Alters the Small Intestinal Microbiota and Bile Acids Without Inducing Intestinal Damage or Delaying Peristalsis in the Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Barbara Hutka ◽  
Bernadette Lázár ◽  
András S. Tóth ◽  
Bence Ágg ◽  
Szilvia B. László ◽  
...  
Keyword(s):  
Small Intestine ◽  
Bile Acids ◽  
Intestinal Microbiota ◽  
Intestinal Bacteria ◽  
Mucosal Inflammation ◽  
Intestinal Damage ◽  
Small Intestinal ◽  
Gi Transit ◽  
Anti Inflammatory ◽  
Conjugated Bile Acids

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) induce significant damage to the small intestine, which is accompanied by changes in intestinal bacteria (dysbiosis) and bile acids. However, it is still a question of debate whether besides mucosal inflammation also other factors, such as direct antibacterial effects or delayed peristalsis, contribute to NSAID-induced dysbiosis. Here we aimed to assess whether ketorolac, an NSAID lacking direct effects on gut bacteria, has any significant impact on intestinal microbiota and bile acids in the absence of mucosal inflammation. We also addressed the possibility that ketorolac-induced bacterial and bile acid alterations are due to a delay in gastrointestinal (GI) transit.Methods: Vehicle or ketorolac (1, 3 and 10 mg/kg) were given to rats by oral gavage once daily for four weeks, and the severity of mucosal inflammation was evaluated macroscopically, histologically, and by measuring the levels of inflammatory proteins and claudin-1 in the distal jejunal tissue. The luminal amount of bile acids was measured by liquid chromatography-tandem mass spectrometry, whereas the composition of microbiota by sequencing of bacterial 16S rRNA. GI transit was assessed by the charcoal meal method.Results: Ketorolac up to 3 mg/kg did not cause any signs of mucosal damage to the small intestine. However, 3 mg/kg of ketorolac induced dysbiosis, which was characterized by a loss of families belonging to Firmicutes (Paenibacillaceae, Clostridiales Family XIII, Christensenellaceae) and bloom of Enterobacteriaceae. Ketorolac also changed the composition of small intestinal bile by decreasing the concentration of conjugated bile acids and by increasing the amount of hyodeoxycholic acid (HDCA). The level of conjugated bile acids correlated negatively with the abundance of Erysipelotrichaceae, Ruminococcaceae, Clostridiaceae 1, Muribaculaceae, Bacteroidaceae, Burkholderiaceae and Bifidobacteriaceae. Ketorolac, under the present experimental conditions, did not change the GI transit.Conclusion: This is the first demonstration that low-dose ketorolac disturbed the delicate balance between small intestinal bacteria and bile acids, despite having no significant effect on intestinal mucosal integrity and peristalsis. Other, yet unidentified, factors may contribute to ketorolac-induced dysbiosis and bile dysmetabolism.

scholarly journals Quantitative sequencing clarifies the role of disruptor taxa, oral microbiota, and strict anaerobes in the human small-intestine microbiome

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jacob T. Barlow ◽  
Gabriela Leite ◽  
Anna E. Romano ◽  
Rashin Sedighi ◽  
Christine Chang ◽  
...  
Keyword(s):  
Small Intestine ◽  
Large Intestine ◽  
Immune Surveillance ◽  
Bacterial Overgrowth ◽  
Small Intestinal Bacterial Overgrowth ◽  
Oral Microbiota ◽  
Absolute Abundance ◽  
Human Small Intestine ◽  
Gi Symptoms ◽  
The Absolute

Abstract Background Upper gastrointestinal (GI) disorders and abdominal pain afflict between 12 and 30% of the worldwide population and research suggests these conditions are linked to the gut microbiome. Although large-intestine microbiota have been linked to several GI diseases, the microbiota of the human small intestine and its relation to human disease has been understudied. The small intestine is the major site for immune surveillance in the gut, and compared with the large intestine, it has greater than 100 times the surface area and a thinner and more permeable mucus layer. Results Using quantitative sequencing, we evaluated total and taxon-specific absolute microbial loads from 250 duodenal-aspirate samples and 21 paired duodenum-saliva samples from participants in the REIMAGINE study. Log-transformed total microbial loads spanned 5 logs and were normally distributed. Paired saliva-duodenum samples suggested potential transmission of oral microbes to the duodenum, including organisms from the HACEK group. Several taxa, including Klebsiella, Escherichia, Enterococcus, and Clostridium, seemed to displace strict anaerobes common in the duodenum, so we refer to these taxa as disruptors. Disruptor taxa were enriched in samples with high total microbial loads and in individuals with small intestinal bacterial overgrowth (SIBO). Absolute loads of disruptors were associated with more severe GI symptoms, highlighting the value of absolute taxon quantification when studying small-intestine health and function. Conclusion This study provides the largest dataset of the absolute abundance of microbiota from the human duodenum to date. The results reveal a clear relationship between the oral microbiota and the duodenal microbiota and suggest an association between the absolute abundance of disruptor taxa, SIBO, and the prevalence of severe GI symptoms.

scholarly journals CAR/Nr1i3 directs T cell adaptation to bile acids in the small intestine

2020 ◽  
Author(s):  
Mei Lan Chen ◽  
Xiangsheng Huang ◽  
Hongtao Wang ◽  
Courtney Hegner ◽  
Yujin Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
Crohn’S Disease ◽  
T Cell ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Bile Acids ◽  
Large Scale ◽  
Enterohepatic Circulation

Bile acids (BAs) are lipid emulsifying metabolites synthesized in hepatocytes and maintained in vivo through enterohepatic circulation between the liver and small intestine1. As detergents, BAs can cause toxicity and inflammation in enterohepatic tissues2. Nuclear receptors maintain BA homeostasis in hepatocytes and enterocytes3, but it is unclear how mucosal immune cells tolerate high BA concentrations in the small intestine lamina propria (siLP). We previously reported that CD4+ T effector (Teff) cells upregulate expression of the xenobiotic transporter MDR1/ABCB1 in the siLP to prevent BA toxicity and suppress Crohn’s disease-like small bowel inflammation4. Here, we identify the nuclear xenobiotic receptor, constitutive androstane receptor (CAR/NR1I3), as a regulator of MDR1 expression in T cells, and safeguard against BA toxicity and inflammation in the small intestine. CAR was activated and induced large-scale transcriptional reprograming in Teff cells infiltrating the siLP, but not the colon. CAR induced expression of detoxifying enzymes and transporters in siLP Teff cells, as in hepatocytes, but also the key anti-inflammatory cytokine, Il10. Accordingly, CAR-deficiency in T cells exacerbated, whereas pharmacologic CAR activation suppressed, BA-driven ileitis in T cell-reconstituted Rag−/− mice. These data suggest that CAR acts locally in small intestinal T cells to detoxify BAs and resolve inflammation. Activation of this program offers an unexpected strategy to treat small bowel Crohn’s disease, and provides evidence of lymphocyte sub-specialization within the small intestine.

Effects of jejunoileal bypass on the enterohepatic circulation of bile acids, bacterial flora in the upper small intestine, and absorption of vitamin B12

Metabolism ◽  
1983 ◽  
Vol 32 (12) ◽  
pp. 1133-1141 ◽  
Author(s):  
Hans Fromm ◽  
Rajendra P. Sarva ◽  
Mark M. Ravitch ◽  
Brittain McJunkin ◽  
Sirus Farivar ◽  
...  
Keyword(s):  
Small Intestine ◽  
Vitamin B12 ◽  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Bacterial Flora ◽  
Jejunoileal Bypass

scholarly journals An Assessment of the Intestinal Lumen as a Site for Intervention in Reducing Body Burdens of Organochlorine Compounds

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ronald J. Jandacek ◽  
Stephen J. Genuis
Keyword(s):  
Small Intestine ◽  
Large Intestine ◽  
Enterohepatic Circulation ◽  
Dietary Lipids ◽  
The Body ◽  
Dietary Fats ◽  
Organochlorine Compounds ◽  
Intestinal Lumen ◽  
Fat Absorption ◽  
Tissue Storage

Many individuals maintain a persistent body burden of organochlorine compounds (OCs) as well as other lipophilic compounds, largely as a result of airborne and dietary exposures. Ingested OCs are typically absorbed from the small intestine along with dietary lipids. Once in the body, stored OCs can mobilize from adipose tissue storage sites and, along with circulating OCs, are delivered into the small intestine via hepatic processing and biliary transport. Retained OCs are also transported into both the large and small intestinal lumen via non-biliary mechanisms involving both secretion and desquamation from enterocytes. OCs and some other toxicants can be reabsorbed from the intestine, however, they take part in enterohepatic circulation(EHC). While dietary fat facilitates the absorption of OCs from the small intestine, it has little effect on OCs within the large intestine. Non-absorbable dietary fats and fat absorption inhibitors, however, can reduce the re-absorption of OCs and other lipophiles involved in EHC and may enhance the secretion of these compounds into the large intestine—thereby hastening their elimination. Clinical studies are currently underway to determine the efficacy of using non-absorbable fats and inhibitors of fat absorption in facilitating the elimination of persistent body burdens of OCs and other lipophilic human contaminants.

scholarly journals Unveiling the Biogeography and Potential Functions of the Intestinal Digesta- and Mucosa-Associated Microbiome of Donkeys

2020 ◽  
Vol 11 ◽  
Author(s):  
Ruiyang Zhang ◽  
Junpeng Zhang ◽  
Wanyi Dang ◽  
David M. Irwin ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Small Intestine ◽  
Large Intestine ◽  
Intestinal Microbiota ◽  
Synergistic Effects ◽  
Potential Functions ◽  
Production Performance ◽  
Limited Information ◽  
Microbial Composition ◽  
Metabolic Functions ◽  
Degrading Bacteria

The intestinal microbial composition and metabolic functions under normal physiological conditions in the donkey are crucial for health and production performance. However, compared with other animal species, limited information is currently available regarding the intestinal microbiota of donkeys. In the present study, we characterized the biogeography and potential functions of the intestinal digesta- and mucosa-associated microbiota of different segments of the intestine (jejunum, ileum, cecum, and colon) in the donkey, focusing on the differences in the microbial communities between the small and large intestine. Our results show that, Firmicutes and Bacteroidetes dominate in both the digesta- and mucosa-associated microbiota in different intestinal locations of the donkey. Starch-degrading and acid-producing (butyrate and lactate) microbiota, such as Lactobacillus and Sarcina, were more enriched in the small intestine, while the fiber- and mucin-degrading bacteria, such as Akkermansia, were more enriched in the large intestine. Furthermore, metabolic functions in membrane transport and lipid metabolism were more enriched in the small intestine, while functions for energy metabolism, metabolism of cofactors and vitamins, amino acid metabolism were more enriched in the large intestine. In addition, the microbial composition and functions in the digesta-associated microbiota among intestinal locations differed greatly, while the mucosal differences were smaller, suggesting a more stable and consistent role in the different intestinal locations. This study provides us with new information on the microbial differences between the small and large intestines of the donkey and the synergistic effects of the intestinal microbiota with host functions, which may improve our understanding the evolution of the equine digestive system and contribute to the healthy and efficient breeding of donkeys.

Sa1930 THE EFFECT OF BILE ACIDS AS A MAJOR REGULATOR OF INTESTINAL MICROBIOTA, ESPECIALLY ON DIFFERENT PARTS OF THE MICE LARGE INTESTINE.

2020 ◽  
Vol 158 (6) ◽  
pp. S-484
Author(s):  
Chang Bum IM ◽  
Ki Hyun Ryu ◽  
Hoon Sup Koo ◽  
Kyung Ho Song ◽  
Sun Moon Kim ◽  
...  
Keyword(s):  
Bile Acids ◽  
Large Intestine ◽  
Intestinal Microbiota ◽  
Different Parts
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