Role of central endpoint adjudication and challenges in trials on neonatal sepsis-a case of ProSPoNS trial.

Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on "sepsis," the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the "physician diagnosed sepsis." To align all the three above, the investigators meeting, held on 17th-18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that "physician diagnosed sepsis" is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine "physician diagnosed sepsis": (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.

A randomized cross-over trial of prebiotics and probiotics in multiple sclerosis: Trial feasibility, supplement tolerability and symptom abatement.

BACKGROUND: Dietary supplements can modulate the gut microbial ecosystem and affect the immune system. This has potential implications for autoimmune diseases, including multiple sclerosis (MS). Prior studies explored tolerability, symptomatic improvement, and immunologic effects of probiotics in people with MS (pwMS), but no study has examined prebiotics in this population or compared prebiotics with probiotics. METHODS: This is a randomized, open-label trial of participants with relapsing-remitting MS on B-cell depletion therapy from two MS centers. 22 participants enrolled in the original cross-over study in which probiotic (Visbiome, containing Lactobacillus, Bifidobacterium and Streptococcus species) or prebiotic (Prebiotin, containing oligofructose enriched inulin) supplementation for 6 weeks was randomized, each followed by a washout period. Due to pandemic-related interruptions and expiration of the study supply of probiotics, another 15 participants enrolled in a single-arm study to receive prebiotic supplementation for 6 weeks followed by a washout period. We assessed supplement tolerability and patient-reported outcomes (PRO) relevant to MS (disability, fatigue, mood, and bowel symptoms) before and after each supplement administration period and each washout period. We bio-archived plasma, serum, peripheral blood mononuclear cells and stool samples at each timepoint for future multi-omic assessment. RESULTS: Prebiotics and probiotics had comparable adherence rates and both supplements were well tolerated in pwMS. Participants on either supplement reported minor adverse events, most of which were mild and self-limited. There was a subjective preference for prebiotics over probiotics. Comparing supplement-associated changes in PRO scores from baseline to 6 weeks post-supplementation, there were significant difference between prebiotics and probiotics for the change in patient-reported global symptom burden (MSRS-R Total) and bowel control (BWCS), but only probiotics statistically improved bowel control from baseline to post-supplementation. CONCLUSION: Supplementation with either prebiotics or probiotics is reasonably well-tolerated and safe. Probiotics improved bowel control, but did not improve other PROs in a 6-week time frame. These data regarding feasibility, tolerability, adherence, and adverse events of supplements will inform future clinical trial designs to definitively compare the efficacy and safety of prebiotics and probiotics. The biological data that will be generated from this study in the future will provide mechanistic insights into the effects of these dietary supplements on MS pathophysiology.

Current Regulatory Issues for the Use of Probiotics.

The chapter provides an overview of the current regulatory challenges surrounding the use of probiotics. It explores the global regulatory landscape, noting the need for uniform regulations across various regions. It emphasizes that these inconsistencies pose challenges for consumers, healthcare professionals, and industry stakeholders. Furthermore, the chapter highlights the ongoing efforts at the Codex Alimentarius to establish harmonized probiotic guidelines. The chapter also discusses labeling regulations, stressing the need for more accurate and comprehensive information on probiotic products to aid in evidence-based decision-making. Finally, it addresses safety concerns, particularly for vulnerable populations like children, and calls for a multi-layered approach to safety assessments. The chapter concludes by advocating harmonizing regulations and guidelines to facilitate probiotics' safer and more effective use.

Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis.

Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.

A Randomized Clinical Trial to Evaluate the Efficacy of an Oral Probiotic in Acne Vulgaris.

The relevance of the gut microbiota in some skin inflammatory diseases, including acne vulgaris, has been emphasized. Probiotics could play a role in the modulation of the microbiota, improving the clinical course of this disease. A 12-week randomized, double-blind, placebo-controlled, clinical trial with patients aged 12 to 30 years with acne vulgaris was conducted. The study product was a capsule composed of the probiotic Lacticaseibacillus rhamnosus (CECT 30031) and the cyanobacterium Arthrospira platensis (BEA_IDA_0074B). Patients with improvement in the Acne Global Severity Scale were 10/34 (29.41%) in the placebo group compared with 20/40 (50%) in the probiotic group (p = 0.03). A significant reduction (p = 0.03) in the number of non-inflammatory acne lesions was observed in the probiotic group (-18.60 [-24.38 to -12.82]) vs the placebo group (-10.54 [-17.43 to -3.66]). Regarding the number of total  lesions, a reduction almost reaching statistical significance (p = 0.06) was observed in the probiotic group (-27.94 [-36.35 to -19.53]) compared with the placebo group (-18.31 [-28.21 to -8.41]). In addition, patients with improvement attending the Global Acne Grading System were 7/34 (20.58%) in the placebo group vs 17/40 (42.50%) in the probiotic group (p = 0.02). The number of adverse events was similar in both groups. The probiotic used in this study was effective and well tolerated, and it should be considered for acne vulgaris patients.

Safety and Effectiveness of Probiotics in Preterm Infants with Necrotizing Enterocolitis.

Although necrotizing enterocolitis is a leading cause of morbidity and mortality among preterm infants, its underlying pathophysiology is not fully understood. Gut dysbiosis, an imbalance between commensal and pathogenic microbes, in the preterm infant is likely a major contributor to the development of necrotizing enterocolitis. In this review, we will discuss the increasing use of probiotics in the NICU, an intervention aimed to mitigate alterations in the gut microbiome. We will review the existing evidence regarding the safety and effectiveness of probiotics, and their potential to reduce rates of necrotizing enterocolitis in preterm infants.

Safety and Effectiveness of Probiotics in Preterm Infants with Necrotizing Enterocolitis.

Although necrotizing enterocolitis is a leading cause of morbidity and mortality among preterm infants, its underlying pathophysiology is not fully understood. Gut dysbiosis, an imbalance between commensal and pathogenic microbes, in the preterm infant is likely a major contributor to the development of necrotizing enterocolitis. In this review, we will discuss the increasing use of probiotics in the NICU, an intervention aimed to mitigate alterations in the gut microbiome. We will review the existing evidence regarding the safety and effectiveness of probiotics, and their potential to reduce rates of necrotizing enterocolitis in preterm infants.

Additive efficacy and safety of probiotics in the treatment of ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND: We aim to report the latest pooled analyses to evaluate the additive efficacy and safety of probiotics in the treatment of ulcerative colitis (UC). METHODS: We systematically searched the relevant literature investigating the efficacy and/or safety of probiotics in patients with UC from PubMed, Embase and Web of Science up to January 2023. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included studies according to the inclusion and exclusion criteria. Any discrepancies throughout these processes were solved by consensus. All statistical analyses were performed by Review Manager version 5.4 and Stata version 15.0. RESULTS: A total of 13 articles were included in the pooled analyses, and the studies were all randomized controlled trials with a total of 930 patients. There were no significant differences between the probiotics and placebo groups concerning demographic and baseline characteristics. For patients with active UC, the probiotic group boosted the remission rate by 87% compared to the placebo group, but failed to reach a statistical difference (OR: 1.87; 95% CI 0.98, 3.57; P = 0.06, I2 = 67%); furthermore, there were no statistical differences in maintenance of clinical remission, clinical response, change in UCDAI scores, or mucosal healing outcomes in the probiotic group compared to the placebo group. For patients in clinical remission, the clinical relapse rates were significantly lower in the probiotic group than in the placebo group (OR: 0.34; 95% CI 0.14, 0.79; P = 0.01). Moreover, this study did not observe a significant difference between the two groups for general adverse events rate (OR: 1.98; 95% CI 0.69, 5.68; P = 0.20). CONCLUSION: Probiotic-assisted therapy may be effective in inhibiting UC recurrence in patients in clinical remission without increasing the risk of treatment-related adverse events; furthermore, probiotics may increase the rate of clinical remission in patients with active UC. However, caution is needed when interpreting the clinical efficacy of probiotics in improving the clinical outcome of patients with active UC.

Clostridium butyricum Bacteremia Associated with Probiotic Use, Japan.

Clostridium butyricum, a probiotic commonly prescribed in Asia, most notably as MIYA-BM (Miyarisan Pharmaceutical Co., Ltd.; https://www.miyarisan.com), occasionally leads to bacteremia. The prevalence and characteristics of C. butyricum bacteremia and its bacteriologic and genetic underpinnings remain unknown. We retrospectively investigated patients admitted to Osaka University Hospital during September 2011-February 2023. Whole-genome sequencing revealed 5 (0.08%) cases of C. butyricum bacteremia among 6,576 case-patients who had blood cultures positive for any bacteria. Four patients consumed MIYA-BM, and 1 patient consumed a different C. butyricum-containing probiotic. Most patients had compromised immune systems, and common symptoms included fever and abdominal distress. One patient died of nonocclusive mesenteric ischemia. Sequencing results confirmed that all identified C. butyricum bacteremia strains were probiotic derivatives. Our findings underscore the risk for bacteremia resulting from probiotic use, especially in hospitalized patients, necessitating judicious prescription practices.

Efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate for improving sensitive skin symptoms.

BACKGROUND: Sensitive skin is a common condition affecting a significant proportion of the population, and there is a growing demand for effective and safe management. AIM: To evaluate the efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate as an optimal care for facial sensitive skin. METHODS: A total of 110 participants (64 in group A and 46 in group B) with facial sensitive skin applied the cream twice daily for 28 days. Group A evaluated their sensitive skin, product efficacy, and product use experience at D0 (15 min), D1, D14, and D28. In group B, skin barrier function-related indicators were measured at baseline and on D1, D7, D14, and D28. Dermatologists evaluated tolerance for all participants. RESULTS: After 28 days of use, in group A, 100% of participants reported mildness and comfort with product use. Participants demonstrated significant improvements in skin barrier function-related indicators, including increased stratum corneum moisture content, reduced erythema index, elevated sebum content, decreased trans-epidermal water loss, and diminished skin redness parameter a* value (all p < 0.05). Dermatologist evaluations revealed excellent tolerance among all participants. CONCLUSION: The panthenol-enriched cream with prebiotics and probiotic lysate exhibited substantial clinical efficacy in ameliorating facial sensitive skin conditions, coupled with a high safety profile.

Comparative efficacy and tolerability of probiotic, prebiotic, and synbiotic formulations for adult patients with mild-moderate ulcerative colitis in an adjunctive therapy: A network meta-analysis.

BACKGROUND & AIMS: Probiotics, prebiotics, and synbiotics (PPS) have been widely used as adjuvant treatments in patients with ulcerative colitis (UC) in recent years. However, the most effective formulations of PPS have yet to be identified. We thus aimed to compare the efficacy and tolerability of different PPS formulations for mild-moderate UC. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane CENTRAL from inception to June 24, 2023 for double-blind randomized controlled trials. We used a frequentist approach in random-effects models for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of evidence. RESULTS: We analysed data from 20 trials involving 1153 patients. The combinations of specific strains of Lactobacillus and Bifidobacterium (CLB) (odds ratio (OR), 3.85; 95 % confidence interval (CI), 1.40-10.60; low certainty) and combinations of specific strains of Lactobacillus, Bifidobacterium, and Streptococcus (CLBS) (OR, 2.20; 95 % CI, 1.47-3.28; low certainty) significantly increased the clinical remission rate in intention-to-treat analysis (ITT) when compared to placebo. Similarly, compared with placebo, the two combinations significantly reduced clinical activity scores (standardized mean difference (SMD), -1.17 (95 % CI, -1.68 to -0.65), low certainty; and SMD, -1.33 (95 % CI, -1.81 to -0.86), low certainty, respectively). Hierarchical cluster analyses showed the two combinations formed clusters with high efficacy (clinical remission in ITT and clinical activity score) and tolerability (withdrawal due to worsening symptoms) within 12 weeks. CONCLUSION: In this systematic review, we found CLB and CLBS demonstrated a clinical benefit in adjuvant treatments, with a comparable tolerability and safety profile to placebo. Further trials are needed. TRIAL REGISTRATION NUMBER: CRD42022344905.

Bacillus licheniformis bloodstream infections associated with oral probiotic administration: Two case reports.

Bacillus licheniformis is a facultative anaerobe, gram-positive, endogenous, spore-forming bacillus. It is included in a probiotic preparation commonly used in clinical practice and is usually safe for oral administration. In this paper, we report two cases of bloodstream infection resulting from using B. licheniformis probiotic preparations for gastrointestinal bleeding. The results suggest that B. licheniformis should be used with caution in people who are immunocompromised and suffering from severe= damage to the intestinal mucosal barrier.

Can Saccharomyces cerevisiae supplementation improve piglets' performance and intestinal health after weaning? / A suplementação com Saccharomyces cerevisiae pode melhorar o desempenho e saúde intestinal de leitões após o desmame?

This study aimed to assess the impact of two commercial Saccharomyces cerevisiae strains (CHY1 and CHY2) on the intestinal health and performance of weaned piglets challenged with enterotoxigenic Escherichia coli during the nursery phase. One hundred ninety-two piglets with an average weight of 6.70 ± 0.92 kilograms were allocated in a randomized block design to one of four treatments: a negative control (C) without E. coli challenge and no yeast supplementation; a positive control (CH) with E. coli challenge and no yeast supplementation; and two treatment groups receiving an E. colichallenge with a CHY1 and CHY2 yeast strain supplementation. The challenge involved inoculating piglets with two dosages of E. coli F4 (106 CFU/ml and 109 CFU/ml) and a saline solution for the C group. Samples of intestinal tissue, blood, and cecal content were collected on the trial's 11th, 28th, and 42nd days. All variables were subjected to analysis of variance, and upon detecting significant differences via the F-test (p < 0.05), Tukey's test was applied to compare treatment means. For the analysis of diarrhea occurrence, the Kruskal-Wallis test was applied. When variables were rejected at a 5% probability level, a Dunn's test was conducted as a post-hoc analysis for paired multiple comparisons (p < 0.05), with statistical significance set at this level. Weaned piglets supplemented with CHY1 exhibited superior performance metrics, including higher average daily gain (15.3% increase), body weight (3.4% increase), feed-to-gain ratio (9.5% increase), and average daily feed intake (12.3% increase) at 28 days compared to the CH group across two different nutritional phases. No discernible effects were observed on measuring blood parameters, intestinal morphology, or cecal short-chain fatty acids. Both yeast-treated groups displayed improved performance during the most challenging periods. However, the CHY1 yeast strain contributed to enhanced piglet performance in the initial 28 days without inducing changes in intestinal morphology.(AU)

O presente estudo teve como objetivo avaliar duas cepas comerciais de Saccharomyces cerevisiae (designadas como CHY1 e CHY2) sob a saúde intestinal e desempenho de leitões desmamados desafiados com Escherichia coli enterotoxigênica durante a fase de creche. Um total de 192 leitões com peso médio 6,70 ± 0.92 quilogramas foram distribuídos em um delineamento em blocos casualizados com quatro tratamentos: um controle negativo (C) sem desafio de E. coli e sem suplementação da levedura; um controle positivo (CH) com desafio de E. coli e sem a suplementação da levedura; e dois grupos com a suplementação das dietas com as cepas comerciais das leveduras intituladas CHY1 e CHY2, juntamente ao desafio de E. coli. O desafio envolveu a inoculação de duas doses de E. coli F4 (106 UFC/ml e 109 UFC/ml) nos leitões e uma inoculação de solução salina para o grupo C. Amostras de tecido intestinal, sangue e conteúdo cecal foram coletadas nos 11º, 28º e 42º dias do experimento. Todas as variáveis foram submetidas a análise de variância e quando detectada diferença significativa pelo teste de F (p<0,05), o teste de Tukey foi aplicado para comparar as médias. Para a avalição da ocorrência de diarreia, o teste de Kruskal-Wallis foi aplicado e quando as variáveis foram rejeitadas ao nível de 5% de probabilidade, o teste de Dunn foi conduzido como uma análise post-hoc para comparações múltiplas (p<0,05) com significância estatística nesse nível. Leitões desmamados suplementados com CHY1 apresentaram métricas de desempenho superiores, incluindo maior ganho de peso diário (aumento de 15.3%), peso vivo (aumento de 3.4%), consumo de ração diário (aumento de 9.5%) e melhor eficiência alimentar (aumento de 12.3%) até os 28 dias de experimento em comparação com o grupo CH. Não foram observados efeitos dos tratamentos sobre os parâmetros sanguíneos mensurados, morfologia intestinal ou ácidos graxos de cadeia curta presentes no conteúdo cecal. Ambos os grupos tratados com leveduras apresentaram melhor desempenho durante os períodos mais desafiadores. No entanto, a cepa de levedura CHY1, especificamente, contribuiu para um melhor desempenho dos leitões nos primeiros 28 dias, sem induzir alterações na morfologia intestinal.(AU)

Septicemia due to Bacillus clausii after the use of probiotics. A complication to keep in mind. / Septicemia por Bacillus clausii posterior al uso de probióticos. Una complicación para tener presente.

Probiotics are live microorganisms that benefit the host in different clinical situations. Bacillus clausii is one of the most frequently used, but it is not without risk. To date, there are few reports of complications secondary to this agent in pediatric patients. OBJECTIVE: To describe the case of an infant who developed after treatment sepsis due to Bacillus clausii. CLINICAL CASE: A 4-month-old female infant of indigenous ethnicity, from a rural area in the interior of Panama, 3 hours away from the nearest health sub-center by canoe, and with protein-calorie malnutrition, presented with acute diarrhea and moderate-severe dehydration, receiving Enterogermina as part of the initial treatment. She was transferred to a tertiary hospital, where she arrived with impaired consciousness, respiratory distress, and signs of shock. The initial blood culture reported growth of methicillin-resistant Staphylococcus aureus (MRSA), the gastrointestinal panel was positive for Clostridiodes difficile, and later serial blood cultures of peripheral blood and central venous catheter confirmed growth of Bacillus clausii. With a torpid evolution and resistance to multiple antibiotic schemes, she died due to multisystem organ failure twelve days after admission. CONCLUSIONS: The use of probiotics as concomitant treatment in patients with some degree of immunosuppression should be administered with caution, considering the presence of risk criteria for complications such as malnutrition or intestinal epithelial damage due to severe diarrhea since they predispose to the development of bacteremia and/or sepsis.

Efficacy and Safety of Probiotics in Geriatric Patients with Constipation: Systematic Review and Meta-Analysis.

BACKGROUND: Probiotics may be an effective alternative to traditional drug therapy for constipation in the elderly. OBJECTIVE: To assess the efficacy and safety of probiotics in managing constipation among the elderly. METHODS: Eight databases were queried for randomized controlled trials (RCTs) investigating probiotics' efficacy in addressing constipation among the elderly until January 2023. The meta-analysis was conducted employing R software version 4.2.2. The Cochrane risk of bias tool was utilized to evaluate the risk of bias, and the GRADE approach was employed to assess the credibility of the evidence concerning the efficacy of probiotics in treating constipation in older individuals. RESULTS: A total of six RCTs involving 444 patients were included. Two studies were rated as low risk of bias. The meta-analysis findings revealed that probiotics, when compared to a placebo, led to an increase in stool frequency (MD = 1.02,95% CI [0.21, 2.07], p<0.05, very low quality), the probiotic group exhibited a notable impact on ameliorating symptoms associated with constipation (OR = 11.28, 95%CI [7.21, 17.64], p < 0.05, very low quality), no significant disparities were observed in terms of efforts to evacuate, manual maneuvers, and the incidence of adverse events (p>0.05). CONCLUSION: The available evidence indicates a degree of uncertainty, ranging from low-to-very low, suggesting the efficacy of probiotics in augmenting bowel frequency and ameliorating constipation-related symptoms among elderly patients with constipation. Nevertheless, given the quality of the studies included, it is advisable to conduct further well-designed investigations with substantial sample sizes to substantiate the findings of this study.

Clinical Trial: Probiotics in Metformin Intolerant Patients with Type 2 Diabetes (ProGasMet).

BACKGROUND: For decades, metformin has been the drug of first choice in the management of type 2 diabetes. However, approximately 2-13% of patients do not tolerate metformin due to gastrointestinal (GI) side effects. Since metformin influences the gut microbiota, we hypothesized that a multi-strain probiotics supplementation would mitigate the gastrointestinal symptoms associated with metformin usage. METHODS AND ANALYSIS: This randomized, double-blind, placebo-controlled, single-center, cross-over trial (ProGasMet study) assessed the efficacy of a multi-strain probiotic in 37 patients with metformin intolerance. Patients were randomly allocated (1:1) to receive probiotic (PRO-PLA) or placebo (PLA-PRO) at baseline and, after 12 weeks (period 1), they crossed-over to the other treatment arm (period 2). The primary outcome was the reduction of GI adverse events of metformin. RESULTS: 37 out of 82 eligible patients were enrolled in the final analysis of whom 35 completed the 32 weeks study period and 2 patients resigned at visit 5. Regardless of the treatment arm allocation, while on probiotic supplementation, there was a significant reduction of incidence (for the probiotic period in PRO-PLA/PLA-PRO: P = 0.017/P = 0.054), quantity and severity of nausea (P = 0.016/P = 0.024), frequency (P = 0.009/P = 0.015) and severity (P = 0.019/P = 0.005) of abdominal bloating/pain as well as significant improvement in self-assessed tolerability of metformin (P < 0.01/P = 0.005). Moreover, there was significant reduction of incidence of diarrhea while on probiotic supplementation in PRO-PLA treatment arm (P = 0.036). CONCLUSION: A multi-strain probiotic diminishes the incidence of gastrointestinal adverse effects in patients with type 2 diabetes and metformin intolerance.

Efficacy and safety of probiotic-supplemented bismuth quadruple therapy for the treatment of Helicobacter pylori infection: a systematic review and meta-analysis.

OBJECTIVE: We performed a meta-analysis to determine whether the addition of probiotics to the bismuth quadruple therapy (BQT) for Helicobacter pylori would improve the incidence of eradication and reduce that of side effects. METHODS: Randomized controlled trials matching the inclusion criteria were collected from PubMed, Embase, Web of Science, and The Cochrane Central Register of Controlled Trials. A Mantel-Haenszel random-effects model was used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the incidences of eradication rate, side effects as a whole, diarrhea, and other side effects. RESULTS: Ten studies were selected for inclusion in the meta-analysis. The pooled RRs for the eradication rates in intention-to-treat and per-protocol analyses of the probiotic group vs. the control group were 1.07 (95% CI: 1.02-1.11) and 1.04 (95% CI: 1.00-1.07), respectively. Probiotic supplementation reduced the incidences of side effects (RR 0.58, 95% CI: 0.37-0.91), diarrhea (RR 0.41, 95% CI: 0.25-0.67), and bitter taste (RR 0.63, 95% CI: 0.40-0.99). CONCLUSIONS: The results of this meta-analysis support the use of probiotics in combination with BQT in the clinical management of patients with H. pylori infection.

No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study.

BACKGROUND AND AIMS: Modulation of the gut microbiome composition with probiotics may have beneficial metabolic effects in pregnant women with obesity. The aim was to investigate the effect of probiotic supplementation during pregnancy on metabolic and inflammatory markers and the body composition of the offspring. METHODS AND RESULTS: A randomized double-blind trial in 50 pregnant women (pre-pregnancy BMI ≥30 and < 35 kg/m2) comparing multi-strain probiotics (Vivomixx®; 450 billion CFU/d) versus placebo from 14 to 20 weeks of gestation until delivery was carried out. Participants were followed with two predelivery visits at gestational week 27-30 and 36-37 and with one postdelivery visit. All visits included fasting blood samples (C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin, C-peptide, glucose, glucagon, and glucagon-like peptide-1 (GLP-1)). At delivery, umbilical cord blood samples were collected (GLP-1 and glucagon). At the postdelivery visit, a dual-energy X-ray absorptiometry (DXA) scan of the newborn was performed. Forty-nine of 50 participants completed the study until delivery, and 36 mother-offspring dyads underwent postdelivery examinations including a DXA scan. There were no significant differences in changes in measured biomarkers between the probiotic versus the placebo group. No differences were found in newborn body composition or GLP-1 and glucagon. GLP-1 measured in umbilical blood samples was positively correlated to fat percent in offspring from the probiotic group. CONCLUSION: In this study of pregnant women with obesity and their newborns, there was no effect of probiotic supplementation in mothers or babies on metabolic or inflammatory biomarkers or on body composition of offspring. This study was registered at clinicaltrials.gov as NCT02508844.