Exploring the casual association between gut microbiome, circulating inflammatory cytokines and chronic pancreatitis: A Mendelian randomization analysis.

It has been established that gut dysbiosis contributed to the pathogenesis of digestive disorders. We aimed to explore the causal relationships between intestinal microbiota, circulating inflammatory cytokines and chronic pancreatitis (CP). Summary statistics of genome-wide association studies (GWAS) of intestinal microbiome was retrieved from the MiBioGen study and the GWAS data of 91 circulating inflammatory cytokines and CP were obtained from the GWAS catalog. The 2-sample bidirectional Mendelian randomization (MR) analysis was performed between gut microbiota, circulating inflammatory cytokines and CP, in which the inverse variance weighted (IVW) method was regarded as the primary analysis approach. To prove the reliability of the causal estimations, multiple sensitivity analyses were utilized. IVW results revealed that genetically predicted 2 genera, including Sellimonas and Eubacteriumventriosumgroup, and plasm C-C motif chemokine 23 (CCL23) level were positively associated with CP risk, while genus Escherichia Shigella, Eubacteriumruminantiumgroup and Prevotella9, and plasma Caspase 8, Adenosine Deaminase (ADA), and SIR2-like protein 2 (SIRT2) level, demonstrated an ameliorative effect on CP. Leave-one-out analysis confirmed the robustness of the aforementioned causal effects and no significant horizontal pleiotropy or heterogeneity of the instrumental variables was detected. However, no association was found from the identified genera to the CP-related circulating inflammatory cytokines. Besides, the reverse MR analysis demonstrated no causal relationship from CP to the identified genera and circulating inflammatory cytokines. Taken together, our comprehensive analyses offer evidence in favor of the estimated causal connections from the 5 genus-level microbial taxa and 4 circulating inflammatory cytokines to CP risk, which may help to reveal the underlying pathogenesis of CP.

Alterations of commensal microbiota are associated with pancreatic cancer.

BACKGROUND: Dysbiosis commonly occurs in pancreatic cancer, but its specific characteristics and interactions with pancreatic cancer remain obscure. MATERIALS AND METHODS: The 16S rRNA sequencing method was used to analyze multisite (oral and gut) microbiota characteristics of pancreatic cancer, chronic pancreatitis, and healthy controls. Differential analysis was used to identify the pancreatic cancer-associated genera and pathways. A random forest algorithm was adopted to establish the diagnostic models for pancreatic cancer. RESULTS: The chronic pancreatitis group exhibited the lowest microbial diversity, while no significant difference was found between the pancreatic cancer group and healthy controls group. Diagnostic models based on the characteristics of the oral (area under the curve (AUC) 0.916, 95% confidence interval (CI) 0.832-1) or gut (AUC 0.856; 95% CI 0.74, 0.972) microbiota effectively discriminate the pancreatic cancer samples in this study, suggesting saliva as a superior sample type in terms of detection efficiency and clinical compliance. Oral pathogenic genera (Granulicatella, Peptostreptococcus, Alloprevotella, Veillonella, etc.) and gut opportunistic genera (Prevotella, Bifidobacterium, Escherichia/Shigella, Peptostreptococcus, Actinomyces, etc.), were significantly enriched in pancreatic cancer. The 16S function prediction analysis revealed that inflammation, immune suppression, and barrier damage pathways were involved in the course of pancreatic cancer. CONCLUSION: This study comprehensively described the microbiota characteristics of pancreatic cancer and suggested potential microbial markers as non-invasive tools for pancreatic cancer diagnosis.

Gut microbiota affects pancreatic fibrotic progression through immune modulation in chronic pancreatitis.

Chronic pancreatitis (CP) is characterized by chronic progressive pancreatic inflammation, which leads to the permanent damage of exocrine and endocrine cells. CP causes irreversible morphological and functional changes, and the clinical manifestations includes abdomen pain, steatorrhea and diabetes. CP induces changes in the composition of gut microbiota that could be used as potential biomarkers for pancreatic fibrosis evaluation. Gut microbiota has emerged as key regulator of immunomodulation and gut microbiota-induced immune activation has not been explored in CP. In current study, we profiled gut microbial signatures in mouse CP model, and found that higher proportion of Streptomyces, Turicibacter, Methylobacterium, Enterococcus and Candidatus_Paenicardiniummore were positively associated with the occurrence of pancreatic fibrosis. We then identified increased CD3+T cells and macrophage infiltration in mouse and human CP tissues by transcriptome sequencing data from GEO database. Subsequently, we demonstrated that fecal microbiota transplantation (FMT) from CP mouse (FMT-CP) exacerbated pancreatic fibrosis by increasing CD4+T cells and macrophage infiltration compared to fecal samples obtained from healthy mouse donor (FMT-HC). Our study describes the link between gut microbiota dysbiosis and immune activation in pancreatic fibrotic progression, and highlights the potential therapeutic roles of FMT and CP treatment.

Microbiome changes associated with acute and chronic pancreatitis: A systematic review.

BACKGROUND: Altered intestinal microbiota has been reported in pancreatic disorders, however, it remains unclear whether these changes alter the course of disease in patients with acute (AP) and chronic pancreatitis (CP), or whether these disease states alter the environment to enable pathogenic microbial composition changes to occur. We undertook a systematic review to characterize the gut microbiome in pancreatitis patients. METHODS: MEDLINE and EMBASE were searched for studies on microbiota in pancreatitis published from January 1, 2000 to June 5, 2020. Animal studies, reviews, case reports, and non-English articles were excluded. A frequency analysis was performed for outcomes reported in ≥2 studies and studies were analyzed for risk of bias and quality of evidence. RESULTS: 22 papers met inclusion criteria; 15 included AP, 7 included CP. No studies were appropriately designed to assess whether alterations in the gut microbiome exacerbate pancreatitis or develop as a result of pancreatitis. We did identify several patterns of microbiome changes that are associated with pancreatitis. The gut microbiome demonstrated decreased alpha diversity in 3/3 A P studies and 3/3 C P studies. Beta diversity analysis revealed differences in bacterial community composition in the gut microbiome in 2/2 A P studies and 3/3 C P studies. Functionally, gut microbiome changes were associated with infectious pathways in AP and CP. Several studies suffered from high risk of bias and inadequate quality. CONCLUSIONS: Detecting differences in microbial composition associated with AP and CP may represent a diagnostic tool. Appropriately controlled longitudinal studies are needed to determine whether microbiome changes are causative or reactive in pancreatitis.

The Gut Microbiome in Patients With Chronic Pancreatitis Is Characterized by Significant Dysbiosis and Overgrowth by Opportunistic Pathogens.

INTRODUCTION: Exocrine pancreatic function is a critical host factor in determining the intestinal microbiota composition. Diseases affecting the exocrine pancreas could therefore influence the gut microbiome. We investigated the changes in gut microbiota of patients with chronic pancreatitis (CP). METHODS: Patients with clinical and imaging evidence of CP (n = 51) were prospectively recruited and compared with twice the number of nonpancreatic disease controls matched for distribution in age, sex, body mass index, smoking, diabetes mellitus, and exocrine pancreatic function (stool elastase). From stool samples of these 153 subjects, DNA was extracted, and intestinal microbiota composition was determined by bacterial 16S ribosomal RNA gene sequencing. RESULTS: Patients with CP exhibited severely reduced microbial diversity (Shannon diversity index and Simpson diversity number, P < 0.001) with an increased abundance of facultative pathogenic organisms (P < 0.001) such as Enterococcus (q < 0.001), Streptococcus (q < 0.001), and Escherichia.Shigella (q = 0.002). The CP-associated changes were independent of exocrine pancreatic insufficiency. Short-chain fatty acid producers, considered protective for epithelia such as Faecalibacterium (q < 0.001), showed reduced abundance in patients with CP. Of 4 additional patients with CP previously treated with antibiotics (ceftriaxone and metronidazole), 3 patients were characterized by distinct Enterococcus overgrowth. DISCUSSION: CP is associated with marked gut microbiota dysbiosis, greatly reduced diversity, and increased abundance of opportunistic pathogens, specifically those previously isolated from infected pancreatic necrosis. Taxa with a potentially beneficial role in intestinal barrier function are depleted. These changes can increase the probability of complications from pancreatitis such as infected fluid collections or small intestinal bacterial overgrowth (see Graphical Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A383).

Disordered Gut Microbiota in Children Who Have Chronic Pancreatitis and Different Functional Gene Mutations.

OBJECTIVES: Chronic pancreatitis (CP) is a serious condition whose pathogenic mechanism is unclear. Interactions of host genetic factors with gut microbiota have a role, but little is known, especially in children with CP (CCP), in which the external factors are less important. Our objective was to identify the main gut microbiota genera in CCP and to characterize the functional mutations of these patients. METHODS: We used 16S rRNA sequencing to compare the gut microbiota of healthy controls with patients who had CCP and different functional gene mutations. RESULTS: CCP is characterized by gut microbiota with remarkably reduced alpha diversity. Receiver operating characteristic curve analyses indicated that the abundances of 6 genera-Faecalibacterium, Subdoligranulum, Phascolarctobacterium, Bifidobacterium, Eubacerium, and Collinsella-were significantly decreased in CCP, with an area under curve (AUC) of 0.92 when considering all 6 genera together. Functional analysis of gut microbiota in CCP indicated reduced ribosomal activity, porphyrin and chlorophyll metabolism, starch and sucrose metabolism, and aminoacyl-tRNA biosynthesis, but an enrichment of phosphotransferase system pathways. The abundance of Butyricicoccus was significantly decreased in CCP in the presence of CFTR mutations when combined with mutations in CASR, CTSB, SPINK1, and/or PRSS1. The abundance of Ruminococcaceae was significantly increased in CCP when there were mutations in CASR, CTSB, SPINK1, and/or PRSS1. Patients with CCP but no gene mutations had greater abundances of Veillonella and reduced abundances of Phascolarctobacterium. DISCUSSION: CCP is associated with a depletion of probiotic gut microbiota, and CCP patients with different functional gene mutations have different gut microbiota.

Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Gut microbiota alterations in chronic pancreatitis (CP) are seldomly described systematically. It is unknown whether pancreatic exocrine insufficiency (PEI) and different etiologies in patients with CP are associated with gut microbiota dysbiosis. METHODS: The fecal microbiota of 69 healthy controls (HCs) and 71 patients with CP were compared to investigate gut microbiome alterations in CP and the relationship among gut microbiome dysbiosis, PEI and different etiologies. Fecal microbiomes were analyzed through 16S ribosomal RNA gene profiling, based on next-generation sequencing. Pancreatic exocrine function was evaluated by determining fecal elastase 1 activity. RESULTS: Patients with CP showed gut microbiota dysbiosis with decreased diversity and richness, and taxa-composition changes. On the phylum level, the gut microbiome of the CP group showed lower Firmicutes and Actinobacteria abundances than the HC group and higher Proteobacteria abundances. The abundances of Escherichia-Shigella and other genera were high in gut microbiomes in the CP group, whereas that of Faecalibacterium was low. Kyoto Encyclopedia of Genes and Genomes pathways (lipopolysaccharide biosynthesis and bacterial invasion of epithelial cells) were predicted to be enriched in the CP group. Among the top 5 phyla and 8 genera (in terms of abundance), only Fusobacteria and Eubacterium rectale group showed significant differences between CP patients, with or without PEI. Correlation analysis showed that Bifidobacterium and Lachnoclostridium correlated positively with fecal elastase 1 (r = 0.2616 and 0.2486, respectively, P < 0.05). CONCLUSIONS: The current findings indicate that patients with CP have gut microbiota dysbiosis that is partly affected by pancreatic exocrine function.

Factors That Affect Prevalence of Small Intestinal Bacterial Overgrowth in Chronic Pancreatitis: A Systematic Review, Meta-Analysis, and Meta-Regression.

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) can complicate chronic pancreatitis (CP) and interfere with management. Its predisposing factors in CP and treatment response are unknown. In this review, we evaluated factors affecting disease burden. METHODS: A computerized search of PubMed and EMBASE databases from inception through May 2019 was done for studies correlating SIBO with CP. Studies were screened, and relevant data were extracted and analyzed. Pooled prevalence, odds ratio (OR), and meta-regression were performed using the random effects model as classically described by Borenstein et al. (2009). SIBO's relation to diabetes mellitus (DM), pancreatic exocrine insufficiency (PEI), narcotic use, and proton-pump inhibitor use was investigated. Treatment response was pooled across studies. P value < 0.05 was considered significant. RESULTS: In 13 studies containing 518 patients with CP, SIBO prevalence was 38.6% (95% confidence interval [CI] 25.5-53.5). OR for SIBO in CP vs controls was 5.58 (95% CI 2.26-13.75). Meta-regression showed that PEI and the diagnostic test used were able to explain 54% and 43% of the variance in SIBO prevalence across studies, respectively. DM and PEI were associated with increased SIBO in CP with OR (2.1, 95% CI 1.2-3.5) and OR (2.5, 95% CI 1.3-4.8), respectively. Symptomatic improvement was reported in 76% of patients after SIBO treatment. DISCUSSION: SIBO complicates 38% of CP with OR of 5.58 indicating a predisposition for this condition. PEI correlates with SIBO in CP and might play a role in pathophysiology. DM and PEI are associated with increased SIBO in CP. Treatment of SIBO may lead to symptomatic improvement.

Possible involvement of Enterococcus infection in the pathogenesis of chronic pancreatitis and cancer.

(Aim) Bacterial infection underlies the pathogenesis of many human diseases, including acute and chronic inflammation. Here, we investigated a possible role for bacterial infection in the progression of chronic pancreatitis. (Materials and Methods) Pancreatic juice was obtained from patients with pancreatic cancer (n = 20) or duodenal cancer/bile duct cancer (n = 16) and subjected to PCR using universal primers for the bacterial 16S ribosomal RNA gene. Bacterial species were identified by PCR using bile samples from four pancreatic cancer patients. PCR products were subcloned into T-vectors, and the sequences were then analyzed. Immunohistochemical and serologic analyses for Enterococcus faecalis infection were performed on a large cohort of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer and on mice with caerulein-induced chronic pancreatitis. The effect of E. faecalis antigens on cytokine secretion by pancreatic cancer cells was also investigated. (Results) We found that 29 of 36 pancreatic juice samples were positive for bacterial DNA. Enterococcus and Enterobacter species were detected primarily in bile, which is thought to be a pathway for bacterial infection of the pancreas. Enterococcus faecalis was also detected in pancreatic tissue from chronic pancreatitis and pancreatic cancer patients; antibodies to E. faecalis capsular polysaccharide were elevated in serum from chronic pancreatitis patients. Enterococcus-specific antibodies and pancreatic tissue-associated E. faecalis were detected in mice with caerulein-induced chronic pancreatitis. Addition of Enterococcus lipoteichoic acid and heat-killed bacteria induced expression of pro-fibrotic cytokines by pancreatic cancer cells in vitro. (Conclusion) Infection with E. faecalis may be involved in chronic pancreatitis progression, ultimately leading to development of pancreatic cancer.

Eikenella corrodens perirenal abscess resulting from a pancreatic fistula in a patient with chronic pancreatitis. Case report and literature review.

We present a case of a right perirenal Eikenella corrodens abscess in a patient with chronic pancreatitis and poor dental hygiene. Endoscopic Retrograde CholangioPancreaticography (ERCP) revealed a pancreatic fistula draining to the right perirenal loge. The patient was treated with broad-spectrum antibiotics, percutaneous drainage and endoscopic stenting of the duct of Wirsung, stopping the supply of the fistula. A full recovery in our patient was observed. Considering the uncommon location of the abscess, a review of the different aetiologies of perirenal abscesses and their distrubution patterns, and the endoscopic treatment of symptomatic pancreatic fistulas seemed worthwhile.

The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI).

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls. METHODS: Thirty-five patients and 31 age-, gender- and smoking status-matched healthy controls were evaluated for SIBO by means of a fasting glucose hydrogen breath test (GHBT). The relationship between SIBO and clinical symptoms in chronic pancreatitis was evaluated. RESULTS: SIBO was present in 15% of chronic pancreatitis patients, while no healthy controls tested positive (P = 0.029). SIBO was more prevalent in those taking pancreatic enzyme replacement therapy (PERT) (P = 0.016), with proton pump inhibitor use (PPI) (P = 0.022) and in those with alcohol aetiology (P = 0.023). Patients with concurrent diabetes were more often SIBO-positive and this was statistically significant (P = 0.009). There were no statistically significant differences in reported symptoms between patients with and without SIBO, with the exception of 'weight loss', with patients reporting weight loss more likely to have SIBO (P = 0.047). CONCLUSION: The prevalence of SIBO in this study was almost 15% and consistent with other studies of SIBO in non-surgical chronic pancreatitis patients. These data support the testing of patients with clinically-relevant PEI unresolved by adequate doses of PERT, particularly in those patients with concurrent diabetes. SIBO can be easily diagnosed therefore allowing more specific and more targeted symptom treatment.

Differences in Gut Microbiota Profiles between Autoimmune Pancreatitis and Chronic Pancreatitis.

Host-derived factors alter gut microenvironment, and changes in gut microbiota also affect biological functions of host. Alterations of gut microbiota have been reported in a wide variety of diseases, but the whole picture of alterations in pancreatic diseases remains to be clarified. In particular, the gut microbiota may be affected by malnutrition or impaired exocrine pancreas function that is associated with pancreatic diseases. We here conducted comprehensive analysis of gut microbiota in patients with type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of the systemic IgG4-related disease, and chronic pancreatitis (CP). The two diseases were selected, because altered immune reactions in AIP and/or long-standing malnutrition in CP may influence the gut microbiota. Fecal samples were obtained from 12 patients with AIP before the steroid therapy and 8 patients with CP. Metagenome DNA was extracted, and microbiota was analyzed by next generation sequencing. Gut microbiota profiles were different between patients with AIP and those with CP; namely, the proportions of Bacteroides, Streptococcus and Clostridium species were higher in patients with CP. The reasons for the increased proportion of these bacterial species remain unknown, but may reflect malabsorption and/or decreased pancreatic enzymes, both of which are associated with CP. Incidentally, the identified Streptococcus species are oral cavity inhabitants and also known as pathogens for endocarditis. Despite the small sample size, this study has shown the differences in gut microbiota profiles between AIP and CP. Comprehensive analysis of the gut microbiota may be useful for the differential diagnosis of pancreatic diseases.

Gut microbiota and pancreatic diseases.

Changes in diet, lifestyle, and exposure to environmental risk factors account for the increased incidence of pancreatic disorders, including acute and chronic pancreatitis, and pancreatic cancer. The role of the microbiota in the development of pancreatic disorders is increasingly acknowledged. The translocation of gut bacteria and endotoxins following gut barrier failure is a key event contributing to the severity of acute pancreatitis, while small intestine bacterial overgrowth is common in patients with chronic pancreatitis and further worsens their symptoms and malnutrition. Specific molecular mimicry link the microbiota and Helicobacter pylori with autoimmune pancreatitis. Changes in the oral microbiota typical of periodontitis seem to be associated with an increased risk of developing pancreatic cancer. The composition of the gut microbiota is also unbalanced in the presence of risk factors for pancreatic cancer, such as obesity, smoking and diabetes. Helicobacter pylori infection, atrophic body gastritis and related decreased gastric acid secretion also seem associated with the risk of pancreatic cancer, although this area needs further research. The link between dysbiosis, immune response and proinflammatory status is most likely the key for these associations. The present review article will discuss current available evidence on the role of gut microbiota in pancreatic disorders, highlighting potential areas for future research.

Prevalence of Small Intestinal Bacterial Overgrowth among Chronic Pancreatitis Patients: A Case-Control Study.

Background. Patients with chronic pancreatitis (CP) exhibit numerous risk factors for the development of small intestinal bacterial overgrowth (SIBO). Objective. To determine the prevalence of SIBO in patients with CP. Methods. Prospective, single-centre case-control study conducted between January and September 2013. Inclusion criteria were age 18 to 75 years and clinical and radiological diagnosis of CP. Exclusion criteria included history of gastric, pancreatic, or intestinal surgery or significant clinical gastroparesis. SIBO was detected using a standard lactulose breath test (LBT). A healthy control group also underwent LBT. Results. Thirty-one patients and 40 controls were included. The patient group was significantly older (53.8 versus 38.7 years; P < 0.01). The proportion of positive LBTs was significantly higher in CP patients (38.7 versus 2.5%: P < 0.01). A trend toward a higher proportion of positive LBTs in women compared with men was observed (66.6 versus 27.3%; P = 0.056). The subgroups with positive and negative LBTs were comparable in demographic and clinical characteristics, use of opiates, pancreatic enzymes replacement therapy (PERT), and severity of symptoms. Conclusion. The prevalence of SIBO detected using LBT was high among patients with CP. There was no association between clinical features and the risk for SIBO.

[[Clinical Relevance Helicobacter Pylori Genotypes in Patients with Chronic Pancreatitis and Concomitant Infections Helicobacter Pylori].]

RELEVANCE: Currently, there is a need to study the genetic diversity of H.pylori in patients with variety of acid-related dis- eases to develop new strategies for the treatment of patients with H.pylori to predict high efficiency of treatment. OBJECTIVE: To assess the effectiveness of schemes of eradication therapy in patients with chronic pancreatitis and concom- itant H.pylori infection. MATERIALS AND METHODS: The study included 108 patients with H.pylori infection: 63 patients had chronic pancreatitis and were concomitant with H.pylori-infection and 45 patients were without chronic pancreatitis and had H.pylori infection with a chronic gastritis. All patients were determined by factors of pathogenicity of H.pylori by immunoblotting. After forming the group randomized patients received eradication therapy scheme I and the scheme I with inclusion of bismuth tripotassium dicitrate. CONCLUSIONS: The effectiveness of H.pylori eradication therapy is dependent on the genetic component of H.pylori. In the presence of H.pylori pathogenicity factors p33, p30, p26, p19, p17 in order to increase the effectiveness of treatment the scheme of eradication therapy I line drugs bismuth tri dicitrate should be included.

Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis.

BACKGROUNDS: The bacterial overgrowth might be associated with chronic pancreatitis. This study was to evaluate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis. METHODS: 36 patients with chronic pancreatitis and 49 healthy controls undergoing the hydrogen (H2)-methane (CH4) lactulose breath test (LBT) were reviewed. The LBT positivity (+) indicating the presence of SIBO, gas types, bowel symptom questionnaire, laboratory and radiologic results were surveyed. The LBT+ was (1) an increase in the breath H2 (≥20 ppm) or CH4 (≥10 ppm) over the baseline or (2) a baseline H2 (≥20 ppm) or CH4 (≥10 ppm) within 90 min after lactulose load. RESULTS: LBT+ was significantly higher in the patients (17/36) than in controls (13/49) (47.2% vs. 26.5%, P < 0.05). During LBT, the H2 levels between 0 and 105 min were significantly higher in patients than in controls. Among LBT+ patients, 11 (64.7%), 1 (5.9%), 5 (29.4%) were in the LBT (H2)+, (CH4)+, (mixed)+ groups, respectively. The LBT+ group had significantly higher scores of flatus than those of the LBT- group. Considering the subtypes of LBT, the LBT (mixed)+ group had higher symptom scores of significance or tendency in hard stool, strain, urgency, and flatus than LBT- group The laboratory and radiologic features were not significantly different between LBT+ and LBT- groups. CONCLUSIONS: SIBO is common in patients in chronic pancreatitis. Especially, excretions of mixed H2 and CH4 appear to be related with deterioration of intestinal symptoms.

[The parietal intestinal microflora in patients with chronic pancreatitis].

The article presents the results of the proximal small intestine parietal microbiocenosis research in patients with chronic pancreatitis by polymerase chain reaction in real time. The study includes an assessment of the pharmacological correction's efficiency in this category of patients.

Small intestinal bacterial overgrowth in patients with chronic pancreatitis.

GOALS: To assess the prevalence of small intestinal bacterial overgrowth (SIBO) in chronic pancreatitis (CP), and analyze factors related with SIBO in CP. BACKGROUND: SIBO is to be considered a factor that worsens symptoms and nutritional status in patients with CP. However, the few studies evaluating the rate of SIBO in CP patients used nonuniform and nonstandardized procedures, and reported a wide range of positivity (0% to 92%). Those studies often investigated CP patients with previous resection surgery (cause of SIBO per se). STUDY: CP patients and controls evaluated for SIBO by the H2 glucose breath test with a standard protocol. For CP patients, the relationship between test results, abdominal symptoms, and clinical and biochemical variables was analyzed. RESULTS: A total of 43 CP patients and 43 controls were enrolled. Of the CP patients, 8 had advanced disease (defined by M-ANNHEIM index) and none had undergone previous surgery. The glucose breath test positivity rate was higher in the CP patients than in the controls (21% vs. 14%), albeit without a significant difference (P=0.57). Mean fasting H2 excretion and mean H2 excretion at 120 minutes also had a trend toward higher levels in CP patients. There were no clinical differences between CP patients with or without SIBO, but there were nutritional differences for lower levels of vitamin D and higher levels of folate in these patients with SIBO. CONCLUSIONS: Our findings suggest that SIBO is not uncommon in uncomplicated CP patients. The lack of a significant difference compared with controls might be due to the study being underpowered. SIBO in CP patients does not seem to be related to peculiar clinical features, but it might affect nutritional status.

Small intestinal bacterial overgrowth is common both among patients with alcoholic and idiopathic chronic pancreatitis.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is known to occur in patients with chronic pancreatitis, particularly of alcoholic etiology. There are, however, scanty data on frequency of SIBO in patients with chronic idiopathic pancreatitis and factors associated with its occurrence. METHODS: 68 patients with chronic pancreatitis and 74 age and gender-matched healthy subjects (HS) were evaluated for SIBO using glucose hydrogen breath test (GHBT). Persistent rise in breath hydrogen 12 ppm above basal (at least two recordings) was diagnostic of SIBO. RESULT: SIBO was diagnosed more often among patients with chronic pancreatitis than controls (10/68 [14.7%] vs. 1/74 controls [1.3%]; p = 0.003). Of 68 patients, 22 (32.3%) had alcoholic and 46 (67.6%) had idiopathic chronic pancreatitis. SIBO was as commonly detected among patients with alcoholic as idiopathic pancreatitis (3/22 [13.6%] vs. 7/46 [15.2%]; p = 0.86). Age, gender, body mass index (BMI), steatorrhoea, pain, analgesic use, pancreatic calcifications and use of pancreatic enzyme supplements had no relationship with the presence of SIBO. Diabetes mellitus tended to be commoner among patients with chronic pancreatitis with than without SIBO (6/10 [60%] vs. 18/58 [31%]; p = 0.07). CONCLUSION: SIBO was commoner among patients with chronic pancreatitis, both alcoholic and idiopathic, than HS. Though presence of SIBO among patients with chronic pancreatitis tended to be commoner among those with diabetes mellitus, there was no relationship with age, gender, BMI, steatorrhoea, pain, analgesic use, pancreatic calcifications and use of pancreatic enzyme supplements.

[The heterogeneity of genetic variants of Helicobacter pylori in patients with various acid-related diseases].

THE PURPOSE OF THE STUDY: To study the genetic diversity of H. pylori in patients with chronic gastritis, peptic ulcer disease, chronic pancreatitis. MATERIALS AND METHODS: The study involved 490 patients with gastric ulcer, duodenal ulcer, chronic superficial gastritis, chronic atrophic gastritis, chronic pancreatitis. Diagnosis of H. pylori infection was carried out by the following methods: morphological, urea breath test serological (determining the concentration of IgG antibodies to H. pylori and immunoblotting) and by polymerase chain reaction. For genotyping of H. pylori using sets of primers with a mixture of CagA, VacA s1/ s2, VacA m1, VacA m2, IceA1, IceA2, BabA. To perform immunoblotting using Anti-Helicobacter pylori EUROLINE-Western blot (IgG), based on the Western blot method using test strips with antigens separated by electrophoresis cell extract H. pylori. Statistical computer processing was performed using software packages Statistic for Windows 6.0. RESULTS: The virulent genotype of H. pylori was determined in 92% cases of duodenal ulcer. In chronic non-atrophic and atrophic gastritis virulent genotypes of H. pylori were not detected. In case of uncomplicated duodenal ulcer we revealed isolated (vacA m2) and combined (vacA s1/ s2) genotypes of H.pylori in 23% of cases, of them monogenotip VacAm2 (vacuolating-associated cytotoxin) was determined in 83%. In complicated duodenal ulcer the combined genotype of H. pylori (vacAs1/ s2; vacAs1/ s2 + vacAm1 + vacAm2; vacAs1/ s2 + vacAm2) and mixed genotype of H. pylori (vacAs1/ s2 + cagA, vacAs1/ s2 + iceA2, vacAm1 + cagA + iceA2) were determined in 77% of the samples. In cases of chronic pancreatitis the vacuolating cytotoxin VacA was detected in 35.7%, such as in the control group it was 81.8%. Genes encoding the production of urease (subunit A) were found in 85.7% of chronic pancreatitis patients, in the control group--54.5%. Genes encoding the synthesis of outer membrane proteins of H. pylori such as p26, p19, p17 were detected in 82.1% of patients with chronic pancreatitis, in patients of the control group--54.5%. H. pylori outer membrane proteins with molecular weights of 30 and 33kDa (p30 and p33) were detected in 85.7% of patients with chronic pancreatitis. CONCLUSION: The bacterium H. pylori, which is the main cause of acid diseases, realizes effect through its pathogenicity factors. Waste products of H. pylori have a direct damaging effect on the mucous membrane of the stomach and duodenum, contributing to the release of lysosomal enzymes, a number of cytokines. They are cause the development of inflammatory processes in the mucosa. Lipopolysaccharide of outer membrane of H. pylori cause immune response of the human body and the development of chronic inflammation at the system level. Set of pathogenicity factors of H. pylori determine the nature and severity of the pathological processes triggered by the bacterium at different levels of the microorganism.