The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Principles and practice of infectious diseases

Treatment of type 2 diabetes: challenges, hopes, and anticipated successes.

Biofilms are aggregate of microorganisms in which cells are frequently embedded within a self-produced matrix of extracellular polymeric substance (EPS) and adhere to each other and/or to a surface. The development of biofilm affords pathogens significantly increased tolerances to antibiotics and antimicrobials. Up to 80% of human bacterial infections are biofilm-associated. Dispersal of biofilms can turn microbial cells into their more vulnerable planktonic phenotype and improve the therapeutic effect of antimicrobials. In this review, we focus on multiple therapeutic strategies that are currently being developed to target important structural and functional characteristics and drug resistance mechanisms of biofilms. We thoroughly discuss the current biofilm targeting strategies from four major aspects—targeting EPS, dispersal molecules, targeting quorum sensing, and targeting dormant cells. We explain each aspect with examples and discuss the main hurdles in the development of biofilm dispersal agents in order to provide a rationale for multi-targeted therapy strategies that target the complicated biofilms. Biofilm dispersal is a promising research direction to treat biofilm-associated infections in the future, and more in vivo experiments should be performed to ensure the efficacy of these therapeutic agents before being used in clinic.

/pdf/targeting-biofilms-therapy-current-research-strategies-and-4lx7cih8ov.pdf

Targeting Biofilms Therapy: Current Research Strategies and Development Hurdles

The aim was to conduct a systematic review and meta-analysis of randomised controlled clinical trials assessing the effect of probiotic, prebiotic or synbiotic supplementation on gut microbiota and glucose control and lipid levels in individuals with diabetes. MEDLINE, EMBASE and the Cochrane Library were searched. The eligibility criteria for the studies was involvement of participants with a diagnosis of type 1 or type 2 diabetes. Metabolic outcomes (glucose control, insulinaemia, and lipid profile) of any probiotic, prebiotic or synbiotic supplementation related to modification of gut microbiota (prebiotics, probiotics and synbiotics) were analysed. We provided a narrative synthesis and meta-analysis of the findings on metabolic outcomes from the studies. Metabolic outcomes were extracted post-intervention and expressed as mean differences (MDs) and 95% CIs between treatment and comparator groups. We pooled the results using a random-effects meta-analysis. The meta-analysis was conducted using Review Manager (RevMan) software. After the removal of duplicates and ineligible studies, 5219 studies were retained for review of titles and abstracts. The number of articles was reduced to 130 by review, for which the full-text articles were obtained and reassessed, 38 of which were included in the final meta-analysis. Overall, the use of prebiotics, probiotics or synbiotics reduced HbA1c levels, but did not reach the threshold for significance (−2.17 mmol/mol, 95% CI −4.37, 0.03; p = 0.05, [−0.20%, 95% CI −0.40 to 0.00; p = 0.05, I2 = 66%]) and had no effect on LDL-cholesterol levels (−0.05 mmol/l; 95% CI −0.14, 0.05, p = 0.35, I2 = 37%). However, their consumption decreased levels of fasting blood glucose (−0.58 mmol/l; 95% CI −0.86, −0.30; p < 0.01, I2 = 60%), total cholesterol (−0.14 mmol/l; 95% CI −0.26, −0.02, p = 0.02, I2 = 39%), triacylglycerols (−0.11 mmol/l; 95% CI −0.20, −0.02, p = 0.01, I2= 21%) and insulinaemia (−10.51 pmol/l; 95% CI −16.68,−4.33, p < 0.01, I2 = 74%), and increased HDL-cholesterol levels (0.04 mmol/l; 95% CI 0.01, 0.07, p < 0.01, I2= 24%). In individuals with diabetes mellitus, supplementation with probiotics, prebiotics or synbiotics improved metabolic variables, although the magnitude of this effect is low. Our results suggest that consumption of probiotics, prebiotics or synbiotics may be a potential adjuvant treatment for improving metabolic outcomes. PROSPERO ID CRD42017080071.

/pdf/the-effect-of-probiotics-prebiotics-or-synbiotics-on-110zudechp.pdf

The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: a systematic review and meta-analysis

Background 
Role of multi-strain probiotic formulations in the management of type 2 diabetes mellitus (T2DM) has rarely been reported. In the present study, the effects of the probiotic formulation, UB0316 (L. salivarius UBLS22, L. casei UBLC42, L. plantarum UBLP40, L. acidophilus UBLA34, B. breve UBBr01, B. coagulans Unique IS2, 5 billion CFU each and fructo-oligosaccharides, 100 mg) in patients with T2DM were assessed.


Methods 
A total of 79 eligible subjects (18–65 years, on stable metformin therapy) were randomly assigned to receive UB0316 or placebo, twice-a-day for 12 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c), secondary were assessment of blood glucose levels, HOMA-IR (homeostatic model assessment of insulin resistance), insulin, body weight, and blood lipids. Quality of life, vital signs, physical investigations, safety and Physician/Subject’s Global assessment were also evaluated.


Results 
Twelve week multi-strain probiotic (UB0316) supplementation significantly reduced HbA1c (7.70 ± 0.79%; p = 0.0023) and weight (67.00 ± 8.82 kg; p < 0.001) as compared to placebo (HbA1c: 8.30 ± 1.35%; weight: 67.60 ± 9.46 kg). The changes recorded in fasting blood glucose (FBG), HOMA-IR, insulin, TC, TG, HDL, and LDL levels were however not significantly altered as compared to placebo. No severe adverse events, abnormal vital and physical signs were reported. The quality of life of T2DM was significantly improved.


Conclusions 
UB0316 significantly improved glycemic control as indicated by the decrease in HbA1c levels. There was also a significant decrease in weight in the probiotic treated subjects as compared to placebo.

/pdf/efficacy-of-ub0316-a-multi-strain-probiotic-formulation-in-3goscxd22o.pdf

Efficacy of UB0316, a multi-strain probiotic formulation in patients with type 2 diabetes mellitus: A double blind, randomized, placebo controlled study.

In this placebo-controlled, double-blind clinical trial, we have investigated the effect of multi-strain probiotic (Bacillus coagulans Unique IS2, Lactobacillus rhamnosus UBLR58, Bifidobacterium lactis UBBLa70, Lactobacillus plantarum UBLP40 (each of 2 billion CFU); Bifidobacterium breve UBBr01, Bifidobacterium infantis UBBI01 (each of 1 billion CFU)) capsule with glutamine (250 mg) on students facing examination stress A total of 80 students (18–24 years) were enrolled and randomised to receive multi-strain probiotic or placebo capsules twice a day for 28 days (ie pre- and during examination) The stress was analysed at the baseline and the end of the treatment by using the perceived stress scale (PSS), depression anxiety stress scale (DASS), and state-trait anxiety inventory (STAI) questionnaire The serum cortisol levels were also determined As a result, at the end of the trial, a total of 74 students completed the study, and those who consumed probiotic capsules showed a significant reduction in PSS, DASS, and STAI scores, and serum cortisol levels from the baseline as compared with placebo No adverse events were reported during the study In conclusion, the multi-strain probiotic is effective in reducing stress associated with examination CTRI/2019/03/018178

Effect of Multi-strain Probiotic Formulation on Students Facing Examination Stress: a Double-Blind, Placebo-Controlled Study

The therapeutic effects of B. coagulans Unique IS2 have been well established in children with irritable bowel syndrome (IBS), but its efficacy in adults remain under reported. Thus, in this study the efficacy of B. coagulans Unique IS2 in the management of IBS symptoms in adults was investigated. Patients (n = 153) fulfilling Rome III criteria were provided placebo capsules for a 2 weeks run-in period. Only patients satisfying compliance criteria (n = 136) were randomized (double blind) to receive either B. coagulans Unique IS2 (2 billion CFU) or placebo capsules daily for 8 weeks. Reduction of abdominal discomfort/pain intensity and increase in complete spontaneous bowel movements were analyzed as primary end points. Other clinical symptoms of IBS and serum cytokines were also evaluated. B. coagulans Unique IS2 showed significant improvement in primary and secondary endpoints, as compared to placebo. Haematology of both the arms remained normal. No significant changes in pro- (IL-6, IL-12, TNF-α, INF- γ) and anti-inflammatory cytokine (IL-10) levels were detected at the end of B. coagulans treatment (8 weeks) as compared to placebo. B. coagulans was well tolerated with no severe adverse events to report. Overall, the results demonstrate that B. coagulans Unique IS2 is efficacious in the management of IBS symptoms in adults (18–60 years).

/pdf/randomized-clinical-trial-the-effect-of-probiotic-bacillus-27860t7umr.pdf

Randomized clinical trial: the effect of probiotic Bacillus coagulans Unique IS2 vs. placebo on the symptoms management of irritable bowel syndrome in adults

Functional constipation has a high prevalence in both adults and children affecting quality of life. Evidence suggests that probiotics can reduce the symptoms of constipation. As the effects of probiotics are strain specific, the efficacy of Bacillus coagulans Unique IS2 in the treatment of functional constipation in adults was evaluated. Subjects (n = 100) diagnosed with functional constipation were supplemented with either B. coagulans Unique IS2 (2 billion CFU) or placebo capsules once daily for 4 weeks. Subjects were evaluated for treatment success (defined as three or more spontaneous stools per week), stool consistency, difficulty of defecation, defecation and abdominal pain. By the end of the fourth week, there was a statistically significant (p < 0.001) increase in number of bowel movements in the probiotic treated group as compared to placebo. Ninety eight percent of subjects in the probiotic group achieved normal stool consistency as compared to placebo (74%). Moreover, there was relief from symptoms of incomplete evacuation, painful defecation and abdominal pain associated with constipation in probiotic treated group as compared to placebo. In conclusion, B. coagulans Unique IS2 significantly decreased the symptoms of constipation indicating effectiveness of the strain in the treatment of constipation.Trial registration: CTRI/2017/11/010539.

Bacillus coagulans Unique IS2 in Constipation: A Double-Blind, Placebo-Controlled Study.

Bacillus clausii UBBC07 is a commercial spore probiotic known to reduce diarrhea in children and adults. In the present study, survival and germination of UBBC07 spores were investigated under fed and fasted conditions in Simulator of Human Intestinal Microbial Ecosystem. Besides this, lantibiotic production, purification, and characterization were performed. The agar plate analysis showed that spores were 100% tolerant to fed and fasted gastrointestinal tract (GIT) conditions. Simultaneously, flow cytometry revealed that at the end of small intestinal incubation, 120% (fed) and 133% (fasted) spores were in viable germinating state. The transformation of viable germinating spores into viable vegetative cells was observed at 3 h of incubation under fasted GIT conditions. In antimicrobial evaluation, UBBC07 produced low-molecular-weight (2107.94 Da) class I lantibiotic clausin. The presence of lanB, lanC, and lanD genes confirms the clausin production. Clausin is stable at proteases (pepsin, proteinase K, and trypsin), temperature (up to 100°C), and pH (up to 11). Furthermore, the antimicrobial activity toward Gram-positive bacteria including Clostridium difficile is advantageous. In conclusion, B. clausii UBBC07 spore probiotic is capable of surviving and germinating under in vitro upper GIT conditions. The clausin production justifies strain applicability in diarrhea.

/pdf/survival-and-germination-of-bacillus-clausii-ubbc07-spores-4zp29z4m12.pdf

Survival and Germination of Bacillus clausii UBBC07 Spores in in vitro Human Gastrointestinal Tract Simulation Model and Evaluation of Clausin Production

Ratna Sudha Madempudi

Papers

Efficacy of UB0316, a multi-strain probiotic formulation in patients with type 2 diabetes mellitus: A double blind, randomized, placebo controlled study.

Effect of Multi-strain Probiotic Formulation on Students Facing Examination Stress: a Double-Blind, Placebo-Controlled Study

Randomized clinical trial: the effect of probiotic Bacillus coagulans Unique IS2 vs. placebo on the symptoms management of irritable bowel syndrome in adults

Bacillus coagulans Unique IS2 in Constipation: A Double-Blind, Placebo-Controlled Study.

Survival and Germination of Bacillus clausii UBBC07 Spores in in vitro Human Gastrointestinal Tract Simulation Model and Evaluation of Clausin Production