Bile Microbiota Research Articles

A Novel Bifidobacterium/Klebsiella Ratio in Characterization Analysis of the Gut and Bile Microbiota of CCA Patients

Cholangiocarcinoma (CCA) is a serious health problem worldwide. The gut and bile microbiota have not been clearly characterized in patients with CCA, and better noninvasive diagnostic approaches for CCA need to be established. The aim of this study was to investigate the characteristics of the gut and bile microbiota in CCA patients. Forty-two CCA patients and 16 healthy normal controls (HNCs) were enrolled. DNA was extracted from fecal and bile samples and subjected to 16S rRNA gene analysis. We found that there were significant differences in the species diversity, structure, and composition of the microbial communities between the CCA group and the HNC grouAt the phylum level, compared with that in the HNC group, the relative abundance of Firmicutes and Actinobacteriota was significantly decreased in the CCA group, whereas Proteobacteria and Bacteroidota were significantly enriched. The Firmicutes/Bacteroidota (F/B) ratio significantly decreased in the CCA group compared to the HNC grouThe relative abundance of Klebsiella in the CCA group was significantly higher than that in the HNC group, while the relative abundance of Bifidobacterium was significantly decreased. The Bifidobacterium/Klebsiella (B/K) ratio was established as a novel biomarker and was found to be significantly decreased in the CCA group compared with the HNC grouOur findings provide evidence supporting the use of Klebsiella and Bifidobacterium as noninvasive intestinal microbiomarkers for improving the diagnosis of CCA.

Bile Microbiome Signatures Associated with Pancreatic Ductal Adenocarcinoma Compared to Benign Disease: A UK Pilot Study

Pancreatic ductal adenocarcinoma (PDAC) has a very poor survival. The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance and, therefore, patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures that can effectively distinguish malignant from benign tumours in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease. Prospective bile samples were obtained from 31 patients who underwent either Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiogram (PTC). Variable regions (V3–V4) of the 16S rRNA genes of microorganisms present in the samples were amplified by Polymerase Chain Reaction (PCR) and sequenced. The cohort consisted of 12 PDAC, 10 choledocholithiasis, seven gallstone pancreatitis and two primary sclerosing cholangitis patients. Using the 16S rRNA method, we identified a total of 135 genera from 29 individuals (12 PDAC and 17 benign). The bile microbial beta diversity significantly differed between patients with PDAC vs. benign disease (Permanova p = 0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering of Aitchison distance. We found three genera to be of significantly lower abundance among PDAC samples vs. benign, adjusting for false discovery rate (FDR). These were Escherichia (FDR = 0.002) and two unclassified genera, one from Proteobacteria (FDR = 0.002) and one from Enterobacteriaceae (FDR = 0.011). In the same samples, the genus Streptococcus (FDR = 0.033) was found to be of increased abundance in the PDAC group. We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.

Any Role for Microbiota in Cholangiocarcinoma? A Comprehensive Review

Alterations in the human microbiota have been linked to carcinogenesis in several cancers. To date, few studies have addressed the role of the microbiota in cholangiocarcinoma (CCA). Our work aims to update the knowledge about the role of the microbiota in the CCA microenvironment, and to highlight possible novel insights for the development of new diagnostic, prognostic, or even therapeutic strategies. We thus conducted a review of the literature. In recent years, great progress has been made in understanding the pathogenesis, the clinical and histological behavior, and the molecular profile of CCA. Much evidence suggests that the bile microbiota plays an essential role in biliary diseases, including CCA. Some studies have demonstrated that alterations in the qualitative and quantitative composition of the intestinal commensal bacteria lead to overall cancer susceptibility through various pathways. Other studies suggest that the gut microbiota plays a role in the pathogenesis and/or progression of CCA. The clinical implications are far-reaching, and the role of the microbiota in the CCA microenvironment may lead to considering the exciting implications of implementing therapeutic strategies that target the microbiota-immune system axis.

Клиническое значение показателей реактивности специфического антибактериального иммунитета к антигенам микробиоты дуоденального содержимого при различных вариантах воспалительной патологии верхнего отдела пищеварительного тракта

The purpose was to study the reactivity of antibacterial immunity to pathogens of duodenal content microbiota in 94 school-age children with inflammatory lesions of the upper digestive tract (UDT). The research The obtained a significant role of specific antibacterial (AB) immunity to antigens of duodenal content microbiota in the course of inflammatory process in the upper gastrointestinal tract (UGIT). It was revealed that during the formation of the combined nature of the inflammatory process in the gastroduodenal zone and the biliary tract, functional changes in antiendotoxin protection are recorded. This is confirmed by a decrease in the concentration of antibodies to antigens of gram (-) pathogens against the background of a pronounced dysbiotic process in the digestive system. A clinical marker of this situation is a more severe course of the disease in this category of patients, often taking on a relapsing character. Conclusions. In a combination of chronic gastroduodenitis (CGD) and cholecystitis (CC), in contrast to the isolated course of CGD, a significant decrease in the concentration of antibodies to antigens of Escherichia coli, Klebsiella pneumonia, glycolipid (GLP) and an expansion of the spectrum of microorganisms in the duodenal content were revealed. The reactivity of specific humoral AB immunity to the bile microbiota reflects the severity of the clinical course of the inflammatory process in the UDT and determines the risk of a recurrent course.

ABO-Incompatible Liver Transplantation under the Desensitization Protocol with Rituximab: Effect on Biliary Microbiota and Metabolites.

Background: ABO-incompatible liver transplantation (ABOi LT) under the desensitization protocol with rituximab had excellent survival outcomes comparable to those of ABO-compatible liver transplantation (ABOc LT). In this work, we explored the effect of ABOi LT on recipients from the perspective of biliary microbiota and metabonomics. Methods: Liver transplant (LT) recipients treated at our center were enrolled in the study. In total, 6 ABOi LT recipients and 12 ABOc LT recipients were enrolled, and we collected their bile five times (during LT and at 2 days, 1 week, 2 weeks and 1 month after LT). The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. Results: We obtained 90 bile samples. Whether in group ABOi LT or ABOc LT, the most common phyla in all of the samples were Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The most common genera were Lactobacillus, Weissella, Klebsiella, Pantoea and Lactococcus. There was no significant difference in the diversity between the two groups at 1 week, 2 weeks and 1 month after LT. However, the biggest disparities between the ABOi LT recipients and ABOc LT recipients were observed 2 days after LT, including increased biodiversity with a higher ACE, Chao1, OBS and Shannon index (p < 0.05), and more Staphylococcus in ABOi LT and binary−Jaccard dissimilarity, which indicated varying β-diversity (p = 0.046). These differences were not observed at 1 week, 2 weeks and 1 month after LT. The principal coordinate analysis (PCoA) revealed that the composition of the bile microbiota did not change significantly within 1 month after LT by longitudinal comparison. In an analysis of the bile components, the metabolites were not significantly different every time. However, four enrichment KEGG pathways were observed among the groups. Conclusion: These findings suggest that ABOi LT under the desensitization protocol with rituximab did not significantly affect the biliary microbiota and metabolites of recipients.

Dysbiosis of the Fecal and Biliary Microbiota in Biliary Tract Cancer.

Characteristic bile duct and gut microbiota have been identified in patients with chronic biliary tract disease. This study aimed to characterize the fecal and bile microbiota in biliary tract cancer (BTC) patients and their relationship. Patients with BTC (n = 30) and benign biliary disease (BBD) without cholangitis (n = 11) were included. Ten healthy, age-matched subjects were also recruited for fecal microbiota comparison. The fecal and bile duct microbiotas were analyzed by sequencing the 16S rRNA gene V3-V4 region. Live bacteria were obtained in the bile from three BTC patients by culture, and metagenomics-based identification was performed. Linear discriminant analysis effect size showed a higher Enterobacteriaceae abundance and a lower Clostridia abundance, including that of Faecalibacterium and Coprococcus, in the BTC patients than in the other subjects. Ten of 17 operational taxonomic units (OTUs) assigned to Enterobacteriaceae in the bile were matched with the OTUs found in the BTC subject fecal samples. Furthermore, a bile-isolated strain possessed the carcinogenic bacterial colipolyketide synthase-encoding gene. Enterobacteriaceae was enriched in the BTC feces, and more than half of Enterobacteriaceae in the bile matched that in the feces at the OTU level. Our data suggests that fecal microbiota dysbiosis may contribute to BTC onset.

Characterization analysis of gut and bile microbiota for cholangiocarcinomas.

e16150 Background: Cholangiocarcinomas (CCAs), which derive from the epithelial cells of the biliary tree, constitute a serious and growing health problem worldwide. Gut and bile microbiota have not been characterized in patients with CCA, and better noninvasive diagnostic approaches for CCA are essential to be established. CA19-9 was the most commonly used tumor marker for CCA; nevertheless, the forecasting performance of CA19-9 remains unsatisfactory. The aim of this study was to investigate the characteristics of gut and bile microbiota combined with CA19-9 in CCA patients. Methods: Fecal samples were collected from 42 CCA patients (16 of the total with Bile samples) and 16 healthy normal controls (HNC). 42 CCA patients were divided into three group according to CA19-9 levels: CCN (CA19-9 negative),CCP (CA19-9 positive: CPL (CA19-9 positive within 10 times) and CPH (CA19-9 positive over 10 times)) groups. DNA was extracted from fecal and bile samples and subjected to 16S rRNA gene analysis. The correlation between gut microbiota and clinical data in CCA group were further analyzed with Spearman rank correlation analysis. Results: Comparing with HNC group, the relative abundance of Firmicutes and Actinobacteriota were significantly decreased, whereas Proteobacteria and Bacteroidota were significantly enriched in CCA group at phylum level (all P &lt; 0.01). Interestingly, Firmicutes/Bacteroidota (F/B) ratio significant decreased in CCA group compared to HNC group(P &lt; 0.05). CA19-9 were inversely correlated with Bifidobacterium, which in turn was associated with Klebsiella in CCA patients. Especially the relative abundance of Klebsiella in CCP group was significantly enriched than CCN group(P &lt; 0.05). Conclusions: Our findings provide evidence supporting Klebsiella may serve as a non-invasive intestinal microbiomarker for CCAs. Combinating with CA19-9, Klebsiella may improve the diagnosis of CCAs as non-invasive approach. Bifidobacterium is likely to be a potential protective factor for anti-tumorgenesis of CCAs.

Gallbladder microbiota composition is associated with pancreaticobiliary and gallbladder cancer prognosis

BackgroundThe microbial population of the intestinal tract and its relationship to specific diseases has been extensively studied during the past decade. However, reports characterizing the bile microbiota are rare. This study aims to investigate the microbiota composition in patients with pancreaticobiliary cancers and benign diseases by 16S rRNA gene amplicon sequencing and to evaluate its potential value as a biomarker for the cancer of the bile duct, pancreas, and gallbladder.ResultsWe enrolled patients who were diagnosed with cancer, cystic lesions, and inflammation of the pancreaticobiliary tract. The study cohort comprised 244 patients. We extracted microbiome-derived DNA from the bile juice in surgically resected gallbladders. The microbiome composition was not significantly different according to lesion position and cancer type in terms of alpha and beta diversity. We found a significant difference in the relative abundance of Campylobacter, Citrobacter, Leptotrichia, Enterobacter, Hungatella, Mycolicibacterium, Phyllobacterium and Sphingomonas between patients without and with lymph node metastasis.ConclusionsThere was a significant association between the relative abundance of certain microbes and overall survival prognosis. These microbes showed association with good prognosis in cholangiocarcinoma, but with poor prognosis in pancreatic adenocarcinoma, and vice versa. Our findings suggest that pancreaticobiliary tract cancer patients have an altered microbiome composition, which might be a biomarker for distinguishing malignancy.

119 Awardee Talk: A Matter of the Heart: The Use of Pulses in Canine and Feline Nutrition

Abstract In the pet food industry, the popularity of plant-based protein sources has risen as consumer demand for grain-free and novel protein sources increase. However, minimal research has been conducted as regards use of pulses and their effects on acceptability and digestibility in canine and feline nutrition. In addition, market shift towards grain-free and pulse-rich diets has presented concerns about the suitability of pulses as viable protein sources. In July 2018, the FDA published a press release discussing a potential link between diets containing legumes and the development of dilated cardiomyopathy (DCM) in dogs. As such, part of our research program has focused on the 1) characterization of the macronutrient composition and protein quality of plant-based protein sources, 2) evaluation of the effects of plant-based protein sources in extruded canine and feline diets on macronutrient digestibility, and modulation of fecal microbiota and metabolites, and 3) determination of the longitudinal effects of high pulse inclusion in diets on taurine status in dogs. Pulse ingredients contained approximately 20% crude protein, and had methionine or tryptophan as the first-limiting amino acids using the precision-fed cecectomized rooster assay. When incorporated in canine and feline diets, pulses did not result in negative effects on macronutrient digestibility or fecal scores. However, shifts in fecal microbial and metabolites were observed in animals fed pulse-based in contrast with animal-based protein diets. The inclusion of 45% green lentils in extruded diets did not cause decreased plasma or whole blood taurine or methionine levels. Additionally, excess taurine was not depleted from these animals in the urine or feces. Taurine status was considered normal in these dogs, despite changes in fecal bile acid concentrations and microbiota. Although we are currently carrying out further research projects investigating potential association of pulse rich diets and canine DCM. Current research findings from our laboratory suggest the inclusion of pulses may not be the causative factor. The use of plant-based proteins as ingredients in canine and feline diets not only meet consumer demand but also provide a valuable, safe, and nutritionally adequate alternative to traditional protein sources.

A study of biliary microbiota in patients with biliary tract disease

Biliary tract disease is associated with many factors: genes, environment, infection, etc. The current changes in biliary flora are thought to be involved in the formation of many gastrointestinal tract diseases. Therefore we want to investigate whether the biliary tract disease has a certain correlation with biliary microecology, and to detect specific strains. Patients who were diagnosed with pancreaticobiliary cancer or benign inflammation were enrolled in this study. Mucosa from specimen or bile samples from endoscopic retrograde cholangiopancretography was utilized to collect for DNA extraction and 16S rRNA gene sequencing, followed by analysis of bile microbiota composition. A total of 52 adults were enrolled, of whom 8 with pancreaticobiliary cancer, 13 with acute inflammation, and 31 with chronic inflammation. We found that pancreaticobiliary cancer patients and bening inflammation patients shared similar stable and permanent dominant species and showed apparent differences in their biliary microbial composition and gene function. We discovered that Lactobacillaceae may potentially play a role in pancreaticobiliary cancer progression. Our data suggested that changes in the microbiota between pancreaticobiliary cancer and benign inflammation may help deepen our understanding of the complex spectrum of different microbiotas involved in the development of pancreaticobiliary cancer.

Bile Microbiota in Liver Transplantation: Proof of Concept Using Gene Amplification in a Heterogeneous Clinical Scenario.

Objective: Historically, bile in the biliary tract has been considered sterile. Most of the series are based on patients with biliary tract diseases or the bile has been obtained with procedures susceptible to contamination.Methods: We evaluated the bile in a heterogeneous cohort of liver donors and recipient patients, with samples obtained in a sterile way, directly from the gallbladder and the common bile duct.Results: We assessed the bile microbiota in six liver donors and in six liver recipients after whole or split liver procedures in adult or pediatric recipients. Bile samples were studied using PCR sequencing of the 16S ribosomal RNA gene amplification (rDNA).Conclusions: We demonstrated that the bile is sterile, thereby ruling this out as a source of contamination following transplant.

Human bile microbiota: A retrospective study focusing on age and gender

AimsThe emerging biliary colonization of microorganisms in patients with biliary diseases may be devastating. Recent evidence suggests that age and gender may influence changes in the microbial composition of gut microbiota. To study the relationship between these parameters on bile microbiota, we retrospectively reviewed positive bile cultures following an endoscopic retrograde cholangiopancreatography (ERCP) in a QA-certified academic surgical unit of a single institution. Methods449 positive bile cultures from 172 Italian patients with diseases of the biliopancreatic system hospitalized from 2006 through 2017 were investigated for aerobic, anaerobic, and fungal organisms. The patients were stratified into four age intervals (22−66, 67−74, 75−81, and 82−93 years) and followed up for five years. ResultsGram-positive bacteria (GPB) was negatively associated with age only in multivariate analysis (Rpartial = −0.114, p = 0.017), with younger patients prone to harbor GPB and older patients likely to have Gram-negative bacteria (GNB). There was a definite link with the male gender using both univariate and multivariate analysis (p < 0.001). Enterococcus spp. was the most common strain identified in patients with GPB except for patients aged 67−74 years for male (95.2%) and female (80.9%) patients. Escherichia coli and Klebsiella spp. were most frequent than others in every group analyzed. Analogous results were found for bacteria Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas spp. and Stenotrophomonas spp. apart of the 2nd quartile. ConclusionsOur study strengthens the bond of age and gender with bile microbiota composition and suggests that further investigations may be required in targeting the aging microbiome. Other studies should also focus on Mediterranean epidemiological characteristics and antibiotic resistance surveillance system strategies

Sphincter of Oddi Laxity Alters Bile Duct Microbiota and Contributes to the Recurrence of Chelodocholithiasis

Background: Chelodocholithiasis is closely associated with bacterial infection and inflammation in the bile ducts. Our previous studies showed that sphincter of Oddi laxity (SOL) significantly altered the bile microbiota and might contribute to biliary stone recurrence. However, the direct association among SOL, bile microbiota, and chelodocholithiasis recurrence has not been well investigated. Methods: We recruited 202 patients with chelodocholithiasis, and obtained the bile samples from the common bile duct. We performed 16S rRNA gene analysis to characterize the bile microbiota, and analyzed the risk factors of chelodocholithiasis. Results: Distinct bile microbial communities were identified in patients with and without SOL with a significantly greater abundance of Rhizobiaceae in SOL patients. SOL patients had a higher risk of biliary stone recurrence with a considerably shorter recurrence time. The abundance of Clostridium was significantly higher in recurrent patients. SOL (P = 0.045, HR = 8.563) and pre-operative gamma-glutamyl transferase level (P = 0.037, HR = 1.002) were two independent risk factors of chelodocholithiasis recurrence. Conclusions: Chelodocholithiasis patients with and without SOL demonstrated significant differences in their microbial communities. SOL is a critical risk factor of chelodocholithiasis recurrence after surgery. The presence of Clostridium is potentially associated with SOL-induced chelodocholithiasis recurrence.

Bile Microbiota in Patients with Pigment Common Bile Duct Stones

BackgroundCommon bile duct (CBD) stone is one of the most prevalent gastroenterological diseases, but the role played by biliary microbiota in the pathogenesis of CBD stones remains obscure. The aim of this study was to investigate the characteristics of the biliary tract core microbiome and its potential association with the formation of pigment stones.MethodsTwenty-eight patients with biliary obstruction of various causes were enrolled. Thirteen had new-onset pigment CBD stone. Of the remaining 15, four had benign biliary stricture, four had gallbladder cancer, three had pancreatic cancer, 3 had distal CBD cancer, and one had hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography was used to collect bile samples for DNA extraction, 16S ribosomal RNA gene sequencing, and bile microbiota composition analysis.ResultsProteobacteria (61.7%), Firmicutes (25.1%), Bacteroidetes (5%), Fusobacteria (4.6%), and Actinobacteria (2.6%) were the most dominant phyla in the bile of the 28 study subjects. A comparison between new-onset choledocholithiasis and other causes of biliary obstruction (controls) showed Enterococcus was found to be significantly abundant in the CBD stone group at the genus level (linear discriminant analysis score = 4.38; P = 0.03). However, no other significant compositional difference was observed.ConclusionThis study demonstrates an abundance of microbiota in bile juice and presents a biliary microbiome composition similar to that of duodenum. The study also shows Enterococcus was significantly abundant in the bile juice of patients with a brown pigment stone than in controls, which suggests Enterococcus may play an important role in the development of pigment stones.

Gallstone Disease, Obesity and the Firmicutes/Bacteroidetes Ratio as a Possible Biomarker of Gut Dysbiosis.

Obesity is a major risk factor for developing gallstone disease (GSD). Previous studies have shown that obesity is associated with an elevated Firmicutes/Bacteroidetes ratio in the gut microbiota. These findings suggest that the development of GSD may be related to gut dysbiosis. This review presents and summarizes the recent findings of studies on the gut microbiota in patients with GSD. Most of the studies on the gut microbiota in patients with GSD have shown a significant increase in the phyla Firmicutes (Lactobacillaceae family, genera Clostridium, Ruminococcus, Veillonella, Blautia, Dorea, Anaerostipes, and Oscillospira), Actinobacteria (Bifidobacterium genus), Proteobacteria, Bacteroidetes (genera Bacteroides, Prevotella, and Fusobacterium) and a significant decrease in the phyla Bacteroidetes (family Muribaculaceae, and genera Bacteroides, Prevotella, Alistipes, Paludibacter, Barnesiella), Firmicutes (genera Faecalibacterium, Eubacterium, Lachnospira, and Roseburia), Actinobacteria (Bifidobacterium genus), and Proteobacteria (Desulfovibrio genus). The influence of GSD on microbial diversity is not clear. Some studies report that GSD reduces microbial diversity in the bile, whereas others suggest the increase in microbial diversity in the bile of patients with GSD. The phyla Proteobacteria (especially family Enterobacteriaceae) and Firmicutes (Enterococcus genus) are most commonly detected in the bile of patients with GSD. On the other hand, the composition of bile microbiota in patients with GSD shows considerable inter-individual variability. The impact of GSD on the Firmicutes/Bacteroidetes ratio is unclear and reports are contradictory. For this reason, it should be stated that the results of reviewed studies do not allow for drawing unequivocal conclusions regarding the relationship between GSD and the Firmicutes/Bacteroidetes ratio in the microbiota.

Sphincter of Oddi laxity alters bile duct microbiota and contributes to the recurrence of choledocholithiasis.

BackgroundCholedocholithiasis is closely associated with bacterial infection and inflammation in the bile duct. Our previous studies showed that sphincter of Oddi laxity (SOL) significantly altered the bile microbiota and might contribute to the recurrence of biliary stones. However, the direct association among SOL, the bile microbiota, and choledocholithiasis recurrence is unclear.MethodsWe prospectively recruited 202 patients with choledocholithiasis, and obtained bile samples from the common bile duct. We performed 16S ribosomal RNA gene analysis to characterize the bile microbiota and analyzed the risk factors for choledocholithiasis.ResultsDistinct bile microbial communities were identified in patients with and without SOL, with a significantly larger abundance of Rhizobiaceae in patients with SOL. Patients with SOL had a higher risk of biliary stone recurrence, with a considerably shorter recurrence time. The abundance of Clostridium was significantly higher in patients with stone recurrence. SOL [P=0.024, hazard ratio (HR) =10.800, 95% confidence interval (CI): 1.377–84.701] was an independent risk factor of choledocholithiasis recurrence.ConclusionsCholedocholithiasis patients with and without SOL demonstrated significant differences in their microbial communities. SOL is a critical risk factor for the recurrence of choledocholithiasis after surgery. The presence of Clostridium may be potentially associated with the recurrence of SOL-induced choledocholithiasis.

Biliary Microbiota and Bile Acid Composition in Cholelithiasis.

Background A functional interplay between BAs and microbial composition in gut is a well-documented phenomenon. In bile, this phenomenon is far less studied, and with this report, we describe the interactions between the BAs and microbiota in this complex biological matrix. Methodology. Thirty-seven gallstone disease patients of which twenty-one with Opisthorchis felineus infection were enrolled in the study. The bile samples were obtained during laparoscopic cholecystectomy for gallstone disease operative treatment. Common bile acid composition was measured by LC-MS/MS. Gallbladder microbiota were previously analyzed with 16S rRNA gene sequencing on Illumina MiSeq platform. The associations between bile acid composition and microbiota were analyzed. Results Bile acid signature and Opisthorchis felineus infection status exert influence on beta-diversity of bile microbial community. Direct correlations were found between taurocholic acid, taurochenodeoxycholic acid concentrations, and alpha-diversity of bile microbiota. Taurocholic acid and taurochenodeoxycholic acid both show positive associations with the presence of Chitinophagaceae family, Microbacterium and Lutibacterium genera, and Prevotella intermedia. Also, direct associations were identified for taurocholic acid concentration and the presence of Actinomycetales and Bacteroidales orders, Lautropia genus, Jeotgalicoccus psychrophilus, and Haemophilus parainfluenzae as well as for taurochenodeoxycholic acid and Acetobacteraceae family and Sphingomonas genus. There were no differences in bile acid concentrations between O. felineus-infected and noninfected patients. Conclusions/Significance. Associations between diversity, taxonomic profile of bile microbiota, and bile acid levels were evidenced in patients with cholelithiasis. Increase of taurochenodeoxycholic acid and taurocholic acid concentration correlates with bile microbiota alpha-diversity and appearance of opportunistic pathogens.

Bile microbiota: new insights into biliary complications in liver transplant recipients

BackgroundBiliary complications represent a major problem associated with liver transplantation. This report represents the first study to use high-throughput 16S ribosomal RNA (rRNA) gene sequencing to assess bile microbiota within bile samples of liver transplant recipients with biliary complications. Our goal in this report was to identify the species and abundance of microbes and examine the potential for microbial involvement of bile in liver transplantation patients with biliary complications.MethodsLiver transplant recipients treated at our center over the period from September 2015 to June 2017 were enrolled in the study. Patients satisfying the inclusion criteria were divided into two groups, control (N=13) and symptom (N=10). Sequencing of 16s rDNA was then performed on bile samples from both groups.ResultsThe main bacterial phyla of bile samples in the symptom group included Proteobacteria (55.19%), Firmicutes (32.36%), Actinobacteria (10.24%) and Bacteroidetes (1.23%) and the main bacterial genera were Pseudomonas (23.31%), Klebsiella (18.42%), Lactococcus (9.61%), Rhodococcus (9.59%) and Rhizobium (5.08%). Proteobacteria and Staphylococcus were enriched in the symptom group (P<0.05), whereas Firmicutes (P<0.05) and Enterococcus (P<0.01) were enriched in the control group. Pathways involved as determined with use of the Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed that metabolism pathways of glyoxylate and dicarboxylate, porphyrin and chlorophyll, arginine and proline, glycine, serine and threonine, as well as the bacterial secretion system were all enriched in bile samples from the symptom group (P<0.05).ConclusionsClear differences exist in microbial species distribution in bile samples from the symptom versus control group. The species and pathways enriched in bile samples within the symptom group may be involved in the pathogenesis of biliary complication after liver transplantation.

Helminths and intestinal microbiota interaction: role in the development of noncommunicable diseases

There is an increase in the prevalence of chronic, noncommunicable diseases, including allergic and autoimmune diseases in developed countries. In this regard, the study of factors modifying the population’s immune response is very important.According to the “old friends” hypothesis , insufficiency of infectious stimulation and decrease in prevalence of helminthiasis are associated with development of noncommunicable diseases. Studies revealed that intestinal parasites modulate the host immune response and alter susceptibility to immunological diseases. It is suggested that one of the pathogenetic mechanisms of immune response modulation by parasites is an increase in the content of gastrointestinal bacteria with anti-inflammatory effect. Advanced technologies of microorganism identification provide a deep insight into the microbiota in different pathologies. The study of changes in the intestine and bile microbiota of the host in helminthiases provides new possibilities for prevention, diagnosis and control of such conditions as chronic inflammatory bowel diseases and allergic diseases. The purpose of this review is to analyze current experimental and clinical data on intestinal microbiota in helminth infections and possible association with development of chronic noncommunicable diseases.

A Preliminary Study of Biliary Microbiota in Patients with Bile Duct Stones or Distal Cholangiocarcinoma.

Background and Objective The distal cholangiocarcinoma (dCCA) is associated with many factors: genes, environment, infection, etc. The current changes in biliary flora are thought to be involved in the formation of many gastrointestinal tract (GIT) diseases, like colon adenocarcinoma. Therefore we want to investigate whether the dCCA has a certain correlation with biliary microecology, and to detect specific strains. Methods A total of 68 adults were enrolled, of whom 8 with dCCA, 16 with recurrent choledocholithiasis, and 44 with the onset of common bile duct stones. Endoscopic Retrograde Cholangiopancretography (ERCP) was utilized to collect bile samples for DNA extraction and 16S rRNA gene sequencing, followed by analysis of bile microbiota composition. Results First, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria are the most dominant phyla in the bile of patients with dCCA and the onset of common bile duct stoes. Secondly, compared with the onset of common bile duct stones patients, we got a significant increase in the phylum Gemmatimonadetes, Nitrospirae, Chloroflexi, Latescibacteria, and Planctomycetes in dCCA patients. Finally, at the genus level, we obtained sequencing results of 252 bacterial genera from patients with dCCA, recurrent choledocholithiasis, and the new onset of common bile duct stones, revealing heterogeneity among individuals. Conclusion To the best of our knowledge, this is the first study of the dysbiosis of bile flora in patients with dCCA. This micro-ecological disorder may be a decisive factor in the formation of dCCA. At the same time, for the first time, this study provides a test chart of biliary microbial populations that may be associated with recurrent choledocholithiasis. The compositional changes of the core microbial group of the biliary tract have potentially important biological and medical significance for the microbiological biliary disorders of dCCA.