Clinical and microbiological aspects of the use of Lactobacillus rhamnosus PL1 strains in proctological patients with symptoms of chronic proctitis.

Recurrent proctitis and the symptoms associated therewith pose significant clinical problem in proctological patients. The objective of this study was to assess the impact of the probiotic Lactobacillus rhamnosus PL1 strain on the clinical presentation and composition of intestinal microbiota in patients with symptoms of proctitis in the course of hemorrhoidal disease and diverticulosis. Material consisted of 24 patients in whom no complete clinical improvement could be obtained after the treatment of the underlying disease. Subject to the assessment was the presence and the intensity of clinical symptoms as well as qualitative and quantitative changes in the composition of bacterial flora detected in the stool before, during and after a 9-week supplementation with the probiotic Lactobacillus rhamnosus PL1 strain. RESULTS: In the entire study group, the intensity of pain after 12 weeks was significantly lower (p=0,.011) compared to baseline; the intensity of flatulence and abdominal discomfort was reduced significantly as early as after 3 weeks, with the difference reaching a highly significant level after 12 weeks (pP<0,.0001). No significant difference was observed in the frequency of the reported episodes of diarrhea, constipation, as well as itching and burning in the anal region. As early as after 3 weeks of supplementation with the probiotic L. rhamnosus PL1 strain, significant qualitative and quantitative changes were observed in the composition of intestinal microbiota; the changes differed depending on the underlying disease. An increase in the total counts of the bacteria of Lactobacillus genus, particularly L. rhamnosus PL1 strain was observed regardless of the underlying disease. CONCLUSION: Tthe probiotic Lactobacillus rhamnosus PL1 strain appears to be useful in restoring appropriate ratios of bacterial populations in patients presenting with symptoms of proctitis in the course of the treatment of certain diseases of the lower gastrointestinal tract.

Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis.

BACKGROUND: Changes within the gut microbiota contribute to the progression of chronic liver diseases. According to the results of several studies performed in animal models, gut dysbiosis plays an important role in hepatocarcinogenesis. The aim of this study was to explore the characteristics of gut microbiota associated with the presence of hepatocellular cancer (HCC) in patients with cirrhosis of the liver undergoing liver transplantation. METHODS: A total of 15 patients with HCC and 15 non-HCC patients matched according to etiology of cirrhosis and Model for End-Stage Liver Disease (MELD) scores who underwent liver transplantations between 2012 and 2014 were included. Analysis of their gut microbial profile was based on prospectively collected stool samples from the pretransplant period. RESULTS: Patients with and without HCC were similar with respect to age (P = .506), sex (P = .700), hepatitis C virus (P > .999) and hepatitis B virus (P = .715) infection status, alcoholic liver disease (P > .999), and MELD score (P = .337). Notably, the presence of HCC was associated with significantly increased fecal counts of Escherichia coli (P = .025). Prediction of HCC presence based on E coli counts was associated with the area under the receiver-operating curve of 0.742 (95% confidence interval, 0.564-0.920), with the optimal cutoff on the level of 17.728 (natural logarithm of colony-forming units per 1 g of feces). Sensitivity and specificity rates for the established cutoff were 66.7% and 73.3%, respectively. CONCLUSIONS: The profile of gut microbiota associated with the presence of HCC in cirrhotic patients is characterized by increased fecal counts of E coli. Therefore, intestinal overgrowth of E coli may contribute to the process of hepatocarcinogenesis.

The relevance of intestinal dysbiosis in liver transplant candidates.

BACKGROUND: The gut microbial ecosystem plays an important role in the pathogenesis of liver diseases. However, the association of microbial community structure with the severity of liver dysfunction is not completely understood. METHODS: Fecal microflora was assessed in 40 patients with liver cirrhosis listed for primary liver transplantation (LT). Independent associations between fecal microbial counts and serum bilirubin, serum creatinine, international normalized ratio (INR), and the Model for End-stage Liver Disease (MELD) score were established in multiple linear regression models. RESULTS: Bifidobacterium (standardized regression coefficient [sß] = -0.549; P < 0.001), Enterococcus (sß = 0.369; P = 0.004), and yeast (sß = 0.315; P = 0.018) numbers were independently associated with serum bilirubin, while Escherichia coli counts (sß = 0.318; P = 0.046) correlated with INR, and Bifidobacterium counts (sß = 0.410; P = 0.009) with serum creatinine. Only Bifidobacterium (sß = -0.468; P = 0.003) and Enterococcus (sß = 0.331; P = 0.029) counts were independent predictors of the MELD score. Bifidobacterium/Enterococcus ratio, proposed as a measure of pre-LT gut dysbiosis, was significantly related to the MELD score following the adjustment for the absolute Bifidobacterium (sß = -0.333; P = 0.029) and Enterococcus (sß = -0.966; P = 0.003) numbers. This pre-transplant dysbiosis ratio (PTDR) was significantly correlated with Enterococcus (R = -0.897; P < 0.001) but not with Bifidobacterium (R = 0.098; P = 0.546) counts. Among the other components of gut microflora, only hydrogen peroxide (H2 O2 )-producing Lactobacillus strains significantly influenced Enterococcus counts (sß = 0.349; P = 0.028) and PTDR (sß = -0.318; P = 0.046). CONCLUSION: While the abundance of both Bifidobacterium and Enterococcus is related to liver dysfunction, the size of the Enterococcus population seems to be the most important determinant of pre-LT gut dysbiosis in cirrhotic patients. The H2 O2 -producing Lactobacillus strains potentially ameliorate this dysbiotic state.

Modification of the circadian pattern of ventricular tachyarrhythmias by beta-blocker therapy.

BACKGROUND: Sudden cardiac death exhibits a circadian variation and predominantly occurs during morning hours, Beta-adrenergic antagonists have shown to blunt this morning peak. However, previous reports studying the effects of beta blockers on the circadian variation did not analyze the underlying cause of sudden cardiac death. It thus remains unclear whether ventricular tachyarrhythmias are influenced by beta-blocker therapy. HYPOTHESIS: This study tested the hypothesis that beta-blocking agents blunt the morning peak of life-threatening ventricular tachyarrhythmias. METHODS: In 87 patients who were treated and monitored with an implantable cardioverter defibrillator, the circadian distribution of ventricular tachyarrhythmias terminated by appropriate shocks was analyzed and compared in those receiving beta blockers versus those not receiving beta-blocker therapy. RESULTS: Tachyarrhythmic episodes in the absence of beta-blocker therapy (n = 344) exhibited a circadian variation with a distinct morning peak (16, 38, 28, and 18% of episodes at 0-6, 6-12, 12-18, and 18-24 h, respectively, p < 0.001). In contrast, tachyarrhythmic episodes during beta-blocker therapy (n = 104) were equally distributed over time (22, 27, 24, and 27% of episodes at 0-6, 6-12, 12-18, and 18-24 h, respectively, p = 0.95). The circadian distribution of episodes was significantly different in patients with and those without beta blockade (p < 0.05). CONCLUSION: Beta-adrenergic antagonists influence the circadian distribution of malignant ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. The blunted morning peak of tachyarrhythmic events during beta blockade supports the hypothesis that a sympathetic surge is involved in the circadian pattern of malignant arrhythmias.

Circadian variation of sustained ventricular tachyarrhythmias terminated by appropriate shocks in patients with an implantable cardioverter defibrillator.

To determine the circadian variation of sustained ventricular tachyarrhythmias, 78 consecutive patients with an implanted cardioverter defibrillator were analyzed with regard to the occurrence of spontaneous shock episodes during a mean follow-up period of 18 +/- 12 months. In 39 patients 207 shock episodes that terminated potentially life-threatening ventricular tachyarrhythmias could be related to an exact time of onset. A circadian variation (p < 0.001) of these events was demonstrated, with a primary morning peak between 7 hours and 11 hours and a secondary, much smaller peak between 16 hours and 20 hours. This finding indicates the relevance of endogeneous or exogeneous triggers in the cause of malignant arrhythmias that potentially lead to sudden cardiac death. Subgroup analyses revealed an association of the circadian pattern to the New York Heart Association functional classification, indicating perhaps a different role of triggers in different patient populations.