Human Gut Microbiota for Diagnosis and Treatment of Depression.

Nowadays, depressive disorder is spreading rapidly all over the world. Therefore, attention to the studies of the pathogenesis of the disease in order to find novel ways of early diagnosis and treatment is increasing among the scientific and medical communities. Special attention is drawn to a biomarker and therapeutic strategy through the microbiota-gut-brain axis. It is known that the symbiotic interactions between the gut microbes and the host can affect mental health. The review analyzes the mechanisms and ways of action of the gut microbiota on the pathophysiology of depression. The possibility of using knowledge about the taxonomic composition and metabolic profile of the microbiota of patients with depression to select gene compositions (metagenomic signature) as biomarkers of the disease is evaluated. The use of in silico technologies (machine learning) for the diagnosis of depression based on the biomarkers of the gut microbiota is given. Alternative approaches to the treatment of depression are being considered by balancing the microbial composition through dietary modifications and the use of additives, namely probiotics, postbiotics (including vesicles) and prebiotics as psychobiotics, and fecal transplantation. The bacterium Faecalibacterium prausnitzii is under consideration as a promising new-generation probiotic and auxiliary diagnostic biomarker of depression. The analysis conducted in this review may be useful for clinical practice and pharmacology.

Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.

Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.

Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study.

BACKGROUND: Rifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain. METHODS: This was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400 mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16 S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman's rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value ≤ 0.05 was considered statistically significant. RESULTS: Of the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p = 0.036) and 6 (p = 0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p = 0.017) and 6 (p = 0.015) months versus baseline. The abundance of Ruminococcaceae (p = 0.034), Veillonellaceae (p = 0.028), and Dialister (p = 0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p = 0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p = 0.003) and Ruminococcaceae (r=-0.371; p = 0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p = 0.022). CONCLUSION: The eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.

Intestinal Barrier and Gut Microbiota in Patients with Overlapping Irritable Bowel Syndrome and Functional Dyspepsia.

BACKGROUND: Disturbances in the intestinal barrier and gut dysbiosis have been observed in patients with functional bowel diseases. AIMS: To investigate the correlation between biomarkers of intestinal barrier disorders at different layers and the severity of symptoms in patients with overlapping diarrhea-predominant irritable bowel syndrome and functional dyspepsia (IDFO), as well as with gut microbiota taxa. METHODS: This study included 45 patients with IDFO and 16 healthy controls. Endoscopy with biopsy of the duodenum and sigmoid colon (SC) was performed to count intraepithelial lymphocytes (IELs) and mucosal eosinophils (subepithelial layer), assess fatty acid binding protein (FABP; epithelial layer) level, and stain for mucin-2 (MUC-2; pre-epithelial layer). Composition of the gut microbiota was evaluated using 16S rRNA gene sequencing. RESULTS: Patients with IDFO exhibited an increase in biomarkers of intestinal barrier disorders at all layers studied. IEL count in the duodenum was correlated with the severity of bloating (r = 0.336; p = 0.024) and, in the SC, was correlated with tenesmus severity (r = 0.303; p = 0.042). FABP-1 level in the SC was correlated with the severity of diarrhea (r = 0.577; p = 0.001), and FABP-5 concentration in the SC was correlated with abdominal distension (r = 0.477; p = 0.010). MUC-2 concentration in the duodenum was correlated with the severity of heartburn (r = 0.572; p = 0.025) and burning sensation in the epigastrium (r = 0.518; p = 0.048). All biomarkers of intestinal barrier permeability were correlated with the abundance of some gut microbiota taxa. CONCLUSION: Patients with IDFO exhibited disrupted intestinal barrier function in all layers, which was associated with clinical symptom severity and changes in the gut microbiota.

Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis.

Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.

The effects of Levilactobacillus brevis on the physiological parameters and gut microbiota composition of rats subjected to desynchronosis.

BACKGROUND: All living organisms have developed during evolution complex time-keeping biological clocks that allowed them to stay attuned to their environments. Circadian rhythms cycle on a near 24 h clock. These encompass a variety of changes in the body ranging from blood hormone levels to metabolism, to the gut microbiota composition and others. The gut microbiota, in return, influences the host stress response and the physiological changes associated with it, which makes it an important determinant of health. Lactobacilli are traditionally consumed for their prophylactic and therapeutic benefits against various diseases, namely, the inflammatory bowel syndrome, and even emerged recently as promising psychobiotics. However, the potential role of lactobacilli in the normalization of circadian rhythms has not been addressed. RESULTS: Two-month-old male rats were randomly divided into three groups and housed under three different light/dark cycles for three months: natural light, constant light and constant darkness. The strain Levilactobacillus brevis 47f was administered to rats at a dose of 0.5 ml per rat for one month and The rats were observed for the following two months. As a result, we identified the biomarkers associated with intake of L. brevis 47f. Changing the light regime for three months depleted the reserves of the main buffer in the cell-reduced glutathione. Intake of L. brevis 47f for 30 days restored cellular reserves of reduced glutathione and promoted redox balance. Our results indicate that the levels of urinary catecholamines correlated with light/dark cycles and were influenced by intake of L. brevis 47f. The gut microbiota of rats was also influenced by these factors. L. brevis 47f intake was associated with an increase in the relative abundance of Faecalibacterium and Roseburia and a decrease in the relative abundance of Prevotella and Bacteroides. CONCLUSIONS: The results of this study show that oral administration of L. brevis 47f, for one month, to rats housed under abnormal lightning conditions (constant light or constant darkness) normalized their physiological parameters and promoted the gut microbiome's balance.

Protective effects of Lactobacillus fermentum U-21 against paraquat-induced oxidative stress in Caenorhabditis elegans and mouse models.

The aims of this work were to identify in vivo manifestations of antioxidant activity of Lactobacillus strains isolated from healthy human biotopes and to show the possibility of protective action of the selected strain on the model of oxidative stress induced by paraquat in the model of early Parkinson's disease (PD) in mice. We studied the protective effects of 14 Lactobacillus strains belonging to five species on the lifespan of the soil nematode Caenorhabditis elegans experiencing oxidative stress induced by paraquat. The Lactobacillus strains used in this study were selected previously based on their ability to reduce oxidative stress in vitro. One of the strains that showed promising results on C. elegans was tested in a mouse model of PD in which C57/BL6 mice were injected regularly with paraquat. We assessed the state of their internal organs, the preservation of dopaminergic neurons in the substantia nigra as well as their motor coordination. The positive impact of Lactobacillus fermentum U-21 strain supplementation on paraquat treated animals was observed. L. fermentum U-21 strain reduced the toxicity of paraquat in C. elegans model: the lifespan of the soil nematode C. elegans was extended by 25%. L. fermentum U-21 protected the mice against anatomical and behavioral changes typical of PD: there were no changes in the coordination of movement and the preservation of dopaminergic neurons in the brain. Life span of the nematode C. elegans pre-grown on a lawn of E. coli OP50 + Lactobacillus under oxidative stress conditions; the concentration of the oxidizing agent paraquat in the S medium was 50 mmol l-1.

The effects of desynchronosis on the gut microbiota composition and physiological parameters of rats.

BACKGROUND: All living organisms experience physiological changes regulated by endogenous circadian rhythms. The main factor controlling the circadian clock is the duration of daylight. The aim of this research was to identify the impact of various lighting conditions on physiological parameters and gut microbiota composition in rats. 3 groups of outbred rats were subjected to normal light-dark cycles, darkness and constant lighting. RESULTS: After 1 and 3 months we studied urinary catecholamine levels in rats; indicators of lipid peroxidation and antioxidant activity in the blood; protein levels of BMAL1, CLOCK and THRA in the hypothalamus; composition and functional activity of the gut microbiota. Subjecting the rats to conditions promoting desynchronosis for 3 months caused disruptions in homeostasis. CONCLUSIONS: Changing the lighting conditions led to changes in almost all the physiological parameters that we studied. Catecholamines can be regarded as a synchronization super system of split-level circadian oscillators. We established a correlation between hypothalamic levels of Bmal1 and urinary catecholamine concentrations. The magnitude of changes in the GM taxonomic composition was different for LL/LD and DD/LD but the direction of these changes was similar. As for the predicted functional properties of the GM which characterize its metabolic activity, they didn't change as dramatically as the taxonomic composition. All differences may be viewed as a compensatory reaction to new environmental conditions and the organism has adapted to those conditions.

Pathogenetic approach to the treatment of functional disorders of the gastrointestinal tract and their intersection: results of the Russian observation retrospective program COMFORT.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of the novel complex drug, consisting of released-active form of antibodies to S-100 protein, tumor necrosis factor-α and histamine, (Kolofort) under outpatient conditions in patients with functional dyspepsia (FD), irritable bowel syndrome (IBS), and FD-IBS overlap. METHODS: The subjects of the observational noninterventional retrospective program were the data of 14,362 outpatient records of patients with diagnosed FD, IBS, and/or overlap, who were observed by gastroenterologists from November 01, 2017, through March 30, 2018, who received the drug Kolofort in monotherapy for 12 weeks, 2 tablets twice a day. To assess the presence and severity of symptoms of functional gastrointestinal disorders (FGID), the "7*7" questionnaire developed by a working group from the Russian Gastroenterological Association was used. The evaluated parameters included the proportion of patients: who had a 50% or more reduction in the total score; who have switched to the less severe category of the condition; who have switched to the "healthy" or "borderline ill" severity categories; and the change in the score in domains 1-7. RESULTS: The final efficacy analysis included data from 9254 patients. A decrease in the total score by 50% or more was observed in 80.45% of patients with FD, 79.02% of patients with IBS, and in 83% of patients with both IBS and FD. Switch to a lower severity category of the condition at the end of therapy was noted in 93.35% of patients with FD, in 93.80% of cases in patients with IBS, and in 96.17% of cases in patients with a combination of IBS and FD. A total of 94 adverse events (AEs) were reported in 80 patients (0.65%). CONCLUSION: The COMFORT program has demonstrated the positive effect of treatment in the majority of patients with IBS and FD and their combination in real clinical practice.

Clinical validation of the "7 × 7" questionnaire for patients with functional gastrointestinal disorders.

BACKGROUND AND AIM: Physicians use different scales and questionnaires to assess the severity of clinical symptoms in patients with functional gastrointestinal disorders. The current study aimed to validate the "7 × 7" questionnaire for assessment of severity of the symptoms as a tool for the efficacy of treatment of functional gastrointestinal disorders, using the Clinical Global Impressions scale as the reference standard. METHODS: Fifty inpatients aged from 18 to 64 with a confirmed diagnosis of irritable bowel syndrome (26 patients, 52%), functional dyspepsia (15 patients, 30%), or both (9 patients, 18%) were prospectively enrolled in the study. We used both the 7 × 7 questionnaire and the Clinical Global Impressions scale before and after 28 days of stable treatment. RESULTS: Our study revealed a significant correlation between the 7 × 7 questionnaire and the Clinical Global Impressions scale results in assessment of severity of the clinical symptoms and their dynamics during treatment. The 7 × 7 questionnaire showed sensitivity of 74.5% and specificity of 54.1% for evaluating patients with mild to severe disease and 66.6% and 76%, respectively, for evaluating patients with moderate to severe disease. The Cronbach's alpha coefficient was 0.719. The intraclass correlation coefficient among participants in whom the condition remained the same was 0.973 (12 participants [24.5%]). CONCLUSIONS: The 7 × 7 questionnaire is a convenient, sensitive, and reliable tool for assessing the severity of symptoms and treatment efficacy in people with functional gastrointestinal disorders.

A bioluminescent test system reveals valuable antioxidant properties of lactobacillus strains from human microbiota.

Oxidative stress cause serious damages in human organism resulting in multiple diseases. Antioxidant therapy includes diet, the use of chemical agents or commensal bacteria such as lactobacilli. This study aims to evaluate the antioxidant (AO) activity of cell-free culture supernatants of lactobacilli, isolated from different parts of the human body. A test system based on Escherichia coli MG1655 strains carrying plasmids encoding luminescent biosensors pSoxS-lux and pKatG-lux inducible by superoxide anion and hydrogen peroxide, respectively, was used to analyze cell-free culture supernatants of lactobacilli. Bioluminescent detection systems are suitable for quick screening of AO activity of lactobacilli. The majority of strains (51 out of 81) belonging to six different species demonstrated various levels of antioxidant activity. This activity was confirmed using the trolox equivalent method. The genome of one of the strains showing high AO activity was sequenced, and the genes putatively involved in AO capacity were determined. Potencies of standard AO and CFS from the most active Lactobacillus strains. Percentages of decrease in the detected luminescence (IAO%) in the presence of AO or CFS are presented. L. br.-L. brevis, L. pl. -L. plantarum, L. rh.-L. rhamnosus.

Expression of the toxin-antitoxin genes yefM(Lrh), yoeB(Lrh) in human Lactobacillus rhamnosus isolates.

Lactobacilli are important microorganisms in various activities, for example, diary products, meat ripening, bread and pickles, but, moreover, are associated directly with human skin and cavities (e.g., mouth, gut, or vagina). Some of them are used as probiotics. Therefore, the molecular biological investigation of these bacteria is important. Earlier we described several toxin antitoxin systems (type II) in lactobacilli. Here, we describe the structure and transcriptional regulation of genes, encoding TA system YefM-YoeB(Lrh) in three strains of Lactobacillus rhamnosus comparing stationary and exponential growth phases, the influence of stress factors and mRNA stability. The same TA system is responding to physiological and stress conditions differently in related strains. Using primer extension and RLM-RACE methods we determined three transcription start sites of RNAs in the operon. The promoter region of the operon is preceded by a conserved BOX element occurring at multiple positions in the genomes of L. rhamnosus strains. Downstream of and partially overlapping with the 3' end of the yoeB(Lrh) toxin gene, a divergently transcribed unexpected RNA was detected.

Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis.

BACKGROUND: The gut-liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate. AIM: To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection. METHODS: This study included 48 patients with Child-Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii) for 3 months. RESULTS: Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child-Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child-Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child-Pugh scores (P = 0.046), as well as a higher level of the Child-Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis. CONCLUSION: The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut-liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.

Efficacy and Safety of a Probiotic Containing Saccharomyces boulardii CNCM I-745 in the Treatment of Small Intestinal Bacterial Overgrowth in Decompensated Cirrhosis: Randomized, Placebo-Controlled Study.

(1) Background: The aim was to evaluate the effectiveness of the probiotic containing Saccharomyces boulardii in the treatment of small intestinal bacterial overgrowth (SIBO) in patients with decompensated cirrhosis. (2) Methods: This was a blinded, randomized, placebo-controlled study. (3) Results: After 3 months of treatment, SIBO was absent in 80.0% of patients in the probiotic group and in 23.1% of patients in the placebo group (p = 0.002). The patients with eliminated SIBO had decreased frequency of ascites and hepatic encephalopathy, the increased platelets and albumin levels, the decreased blood levels of total bilirubin, biomarkers of bacterial translocation (lipopolysaccharide [LPS]) and systemic inflammation (C-reactive protein), and positive changes in markers of hyperdynamic circulation compared with the state at inclusion. There were no significant changes in the claudin 3 level (the intestinal barrier biomarker) in these patients. No significant changes were observed in the group of patients with persistent SIBO. The serum level of nitrate (endothelial dysfunction biomarker) was lower in patients with eradicated SIBO than in patients with persistent SIBO. One (5.3%) patient with eradicated SIBO and six (42.9%) patients with persistent SIBO died within the first year of follow-up (p = 0.007). (4) Conclusions: SIBO eradication was an independent predictor of a favorable prognosis during the first year of follow-up.

Gut Microbiota and Biomarkers of Intestinal Barrier Damage in Cirrhosis.

Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut microbiota in cirrhosis. The blood levels of DAO were inversely correlated with blood levels of claudin 3, lipopolysaccharide (LPS), presepsin, TNF-α, and the severity of cirrhosis according to Child-Pugh scores. The blood level of I-FABP was directly correlated with the blood level of claudin 3 but not with that of DAO. Patients with small intestinal bacterial overgrowth (SIBO) had lower DAO levels than patients without SIBO. There was no significant difference in claudin 3 levels and I-FABP detection rates between patients with and without SIBO. The DAO level was directly correlated with the abundance of Akkermansiaceae, Akkermansia, Allisonella, Clostridiaceae, Dialister, Lactobacillus, Muribaculaceae, Negativibacillus, Ruminococcus, Thiomicrospiraceae, Verrucomicrobiae, and Verrucomicrobiota; and it was inversely correlated with the abundance of Anaerostipes, Erysipelatoclostridium, and Vibrio. The I-FABP level was directly correlated with Anaerostipes, Bacteroidia, Bacteroidota, Bilophila, Megamonas, and Selenomonadaceae; and it was inversely correlated with the abundance of Brucella, Pseudomonadaceae, Pseudomonas, and Vibrionaceae. The claudin 3 level was directly correlated with Anaerostipes abundance and was inversely correlated with the abundance of Brucella, Coriobacteriia, Eggerthellaceae, and Lactobacillus.

ClpL Chaperone as a Possible Component of the Disaggregase Activity of Limosilactobacillus fermentum U-21.

The L. fermentum U-21 strain, known for secreting chaperones into the extracellular milieu, emerges as a promising candidate for the development of novel therapeutics termed disaggregases for Parkinson's disease. Our study focuses on characterizing the secreted protein encoded by the C0965_000195 locus in the genome of this strain. Through sequence analysis and structural predictions, the protein encoded by C0965_000195 is identified as ClpL, homologs of which are known for their chaperone functions. The chaperone activity of ClpL from L. fermentum U-21 is investigated in vivo by assessing the refolding of luciferases with varying thermostabilities from Aliivibrio fischeri and Photorhabdus luminescens within Escherichia coli cells. The results indicate that the clpL gene from L. fermentum U-21 can compensate for the absence of the clpB gene, enhancing the refolding capacity of thermodenatured proteins in clpB-deficient cells. In vitro experiments demonstrate that both spent culture medium containing proteins secreted by L. fermentum U-21 cells, including ClpL, and purified heterologically expressed ClpL partially prevent the thermodenaturation of luciferases. The findings suggest that the ClpL protein from L. fermentum U-21, exhibiting disaggregase properties against aggregating proteins, may represent a key component contributing to the pharmabiotic attributes of this strain.

Efficacy and Safety of Postbiotic Contained Inactivated Lactobacillus reuteri ( Limosilactobacillus reuteri ) DSM 17648 as Adjuvant Therapy in the Eradication of Helicobacter pylori in Adults With Functional Dyspepsia: A Randomized Double-Blind Placebo-Controlled Trial.

INTRODUCTION: Increasing the effectiveness of eradication therapy is an important task in gastroenterology. The aim of this study was to evaluate the efficacy and safety of postbiotic containing inactivated (nonviable) Limosilactobacillus (Lactobacillus) reuteri DSM 17648 (Pylopass) as adjuvant treatment of Helicobacter pylori eradication in patients with functional dyspepsia (FD). METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel study included H. pylori -positive patients with FD. The postbiotic group received Pylopass 200 mg bid for 14 days in combination with eradication therapy (esomeprazole 20 mg bid + amoxicillin 1,000 mg bid + clarithromycin 500 mg bid for 14 days) and another 14 days after the completion of eradication therapy. The study was registered in the ISRCTN registry (ISRCTN20716052). RESULTS: Eradication efficiency was 96.7% for the postbiotic group vs 86.0% for the placebo group ( P = 0.039). Both groups showed significant improvements in quality of life and reduction of most gastrointestinal symptoms with no significant differences between groups. The overall number of digestive adverse effects in the postbiotic group was lower than in the placebo group. Serious adverse effects were not registered. DISCUSSION: The postbiotic containing inactivated L. reuteri DSM 17648 significantly improves the effectiveness of H. pylori eradication therapy in FD and decreases overall number of digestive adverse effects of this therapy.

Gut Microbiota and Cytokine Profile in Cirrhosis.

Background and Aims: Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them. Methods: In the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing. Results: Levels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus. Conclusions: The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.

Effect of Saccharomyces boulardii on Liver Diseases: A Systematic Review.

We aimed to systematize the results of published studies on the use of Saccharomyces boulardii (SB) for the treatment of various liver disorders (CRD42022378050). Searches were conducted using PubMed and Scopus on 1 August 2022. The PubMed search was updated on 15 June 2024. The review included sixteen studies: ten experimental animal studies (EASs) and six randomized controlled trials (RCTs). The CNCM I-745 strain was used in 68.8% of the included studies. SB reduced the severity of many manifestations of cirrhosis, and lowered the Child-Pugh scores in RCT. SB reduced the serum concentrations of TNF-α, IL-1ß, IL-6, and IL-4 in animals with metabolic dysfunction-associated steatotic liver disease (MASLD); lowered the serum TNF-α and IL-6 levels in experimental cirrhosis in rats; and reduced the CRP levels in decompensated cirrhosis. The EAS of MASLD revealed that SB reduced liver steatosis and inflammation and lowered the liver expression of genes of TNF-α, IL-1ß, interferon-γ, and IL-10. In studies on experimental cirrhosis and MASLD, SB reduced the liver expression of genes of TGF-ß, α-SMA, and collagen as well as liver fibrosis. SB reduced the abundance of Escherichia (Proteobacteria), increased the abundance of Bacteroidetes in the gut microbiota, prevented an increase in intestinal barrier permeability, and reduced bacterial translocation and endotoxemia.

Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study. METHODS: This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years. RESULTS: SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis. CONCLUSIONS: SIBO is associated with poor prognosis in cirrhosis.