Lactobacillus reuteri

BACKGROUND: This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of probiotics in reducing H. pylori colonization in non-antibiotic interventions. METHODS: Systematic searches were conducted in PubMed, Scopus, Cochrane Library databases and Google Scholar. Data analysis was performed using CMA (V4) and Trial Sequential Analysis (TSA), with evidence certainty evaluated via GRADE. RESULTS: Twenty-eight studies met the inclusion criteria. Compared with placebo, probiotic monotherapy significantly reduced H. pylori colonization (RR = 1.712, 95 % CI: 1.240 to 2.364, I2 = 37.80, p = 0.001), but total eradication was 16.8 %. Among the probiotic strains, Lactobacillus reuteri showed higher efficacy (event rate = 0.377, 95 % CI: 0.123 to 0.722, I2 = 86.00). 4 weeks supplementation period yielded a stronger effect (event rate = 0.315, 95 % CI: 0.137 to 0.570, I2 = 78.18). Changes in 13C-UBT values, indicating bacterial load reduction, were significant (SMD = -0.617, p < 0.001, 95 % CI: -0.921 to -0.312, I2 = 86.50), while gastrointestinal symptom relief scores showed moderate improvement (SMD = -0.253, p = 0.012, 95 % CI: -0.451 to -0.055, I2 = 2.46). TSA validated that sufficient studies supported these findings, with evidence graded of moderate certainty. CONCLUSION: While probiotic monotherapy, particularly L. reuteri appears to reduce H. pylori colonization and improve gastrointestinal symptoms, their effectiveness as a standalone therapy remains limited owing to low eradication rates and variability in study quality. Further well-designed trials are required to establish their optimal role, particularly as supportive or adjunctive interventions.

INTRODUCTION: Some preclinical and clinical studies have demonstrated the positive effect of Lactobacillus reuteri (L. reuteri) supplementation on depressive symptoms. We conducted an updated systematic review on this topic. METHOD: PubMed, EMBASE, Cochrane, Web of Science, and international trial registries were searched. We included randomized controlled trials (RCTs) and animal experiments on the use of mixed probiotics containing L. reuteri in the treatment of depression. Analyses were done using Review Manager version 5.4 and Stata 18.0. RESULTS: In total, 12 RCTs including 1258 patients were included. The efficacy of the mixed probiotics containing L. reuteri in the treatment of depression was superior to the control group (SMD: -0.44, 95 %CI: -0.72 to -0.16). In terms of acceptability, there was no significant difference between the probiotic and control groups (OR: 1.04, 95 %CI: 0.75 to 1.45). In 9 animal experiments, mixed probiotics containing L. reuteri improved the symptoms of anxiety and depression. Subgroup analyses showed patients using multi-strain interventions (SMD: -0.56, 95 %CI: -0.97 to -0.15), having depressive symptoms (SMD: -0.39, 95 %CI: -0.74 to -0.03), and other clinical populations (SMD: -0.59, 95 %CI: -1.06 to -0.13), age < 60 years (SMD: -0.52, 95 %CI: -0.88 to -0.15), female patients (SMD: -0.45, 95 %CI: -0.78 to -0.13) may benefit more. CONCLUSION: Mixed probiotics containing L. reuteri ameliorated depressive symptoms in patients and depression-like behaviors in animals. Combined microbiota seems to be more effective than single strain intervention in the treatment of depression. Patients with depressive symptoms, other clinical populations, age < 60 years, female patients may benefit more from probiotics. L. reuteri alone did not improve depressive symptoms.

AIM: This study is a systematic review and meta-analysis of randomised controlled trials that employed probiotics and symbiotics for treating infantile colic. METHODS: We performed electronic systematic literature searches in Embase, PubMed and Web of Science, to identify articles published between 1950 and April 2023. Only RCT involving infants with infantile colic under 3 months were included. The treatment plan comprised 15 probiotics, which included Lactobacillus reuteri DSM 17938 and Bifidobacterium animalis lactis BB-12. The probiotics were administered alone or in combination with a prebiotic, vs. no intervention or a placebo. RESULTS: Probiotics resulted in an average reduction of 51 min of crying per day (p = 0.001). Further analysis of subgroups showed that the reduction was -39.30 min for vaginal delivery (p = 0.003), -64.66 min for Lactobacillus reuteri DSM 17938 (p = 0.03), -40.45 min for other strains (p < 0.00001), -74.28 min for exclusively breastfed infants (p = 0.0003) and -48.04 min for mixed feeding (p < 0.00001). CONCLUSION: All probiotic strains seem effective in treating infantile colic. Exclusively breastfed infants have demonstrated more significant reduction in crying time. However, the available evidence on the effectiveness of probiotics in formula-fed and caesarean-born infants is limited. © 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

BACKGROUND: Our previous strain-specific systematic review (SR) showed that Lactobacillus reuteri (LR) DSM 17938 reduces necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and time to full feeds (TFF) in preterm infants. Considering progress in the field over the past 6 years, we aimed to update our SR. METHODS: SR of randomized controlled trials (RCTs) and non-RCTs was conducted. MEDLINE, Embase, Emcare, Cochrane CENTRAL, and gray literature were searched in June 2023. Primary outcomes were TFF, NEC stage ≥II, LOS, and all-cause mortality. Meta-analysis was performed using random-effects model. Certainty of evidence (CoE) was summarized using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. Trial sequential analysis (TSA) was applied for outcome of NEC in RCTs. RESULTS: Twelve RCTs (n = 2284) and four non-RCTs (n = 1616) were included. Six RCTs and three non-RCTs were new. Meta-analysis of RCTs showed LR significantly reduced TFF (mean difference, -2.70 [95% CI, -4.90 to -1.31] days; P = 0.0001), NEC stage ≥II (risk ratio [RR], 0.57 [95% CI, 0.37-0.87]; P = 0.009; eight RCTs), and LOS (RR, 0.72 [95% CI, 0.54-0.97]; P = 0.03); but not mortality (RR, 0.76 [95% CI, 0.54-1.06]; P = 0.10). TSA showed diversity-adjusted required information size (DARIS) as 3624 for NEC. Overall CoE was "very low." Meta-analysis of non-RCTs showed LR reduced NEC (odds ratio, 0.34 [95% CI, 0.15-0.77]; P = 0.01) but not LOS. LR had no adverse effects. CONCLUSIONS: Very low CoE suggests that LR DSM 17938 may reduce NEC and LOS and shorten TFF in preterm infants. Additional RCTs are required to confirm our findings. © 2023 American Society for Parenteral and Enteral Nutrition.

OBJECTIVE: To summarize the effect of adding Lactobacillus reuteri in the treatment plan for diarrheal disease in children, and analyze the potential of probiotics in preventing the occurrence of diarrheal disease. METHODS: Search for randomized controlled trials of Lactobacillus reuteri for the treatment and prevention of diarrhea in the Pubmed, Web of science, Medline, and Cochrane databases. Data such as the number of diarrhea patients, time, length of stay, clinical symptoms and effect of diarrhea prevention were extracted for meta-analysis. Relative risk and confidence interval (RR and 95% CI) were used as outcome indicators. RESULTS: 963 participants in the 9 RCTs came from multiple countries/regions. Compared with placebo/no intervention, the number of diarrhea patients in the Lactobacillus reuteri group was significantly reduced on the day 1 (RR = 0.87, 95%CI: 0.78-0.97) and day 2 (RR = 0.61, 95%CI: 0.44-0.83). Cumulative statistics analysis showed that the effect was stable and significant starting on the 4th day after treatment. A few studies have shown that Lactobacillus reuteri can reduce the time of diarrhea, the number of days with watery stools, and days of hospital stay. However, it has no effect on the occurrence of nosocomial diarrhea (RR = 1.11, 95%CI: 0.68-1.83), rotavirus diarrhea (RR = 1.46, 95%CI: 0.78-2.72), antibiotic-related diarrhea (RR = 1.76, 95%CI: 0.77-4.05), and diarrhea (RR = 1.35, 95%CI: 0.95-1.92). CONCLUSION: Addition of Lactobacillus reuteri in the treatment plan has a significant effect on reducing the number of diarrhea and reducing the symptoms of diarrhea, but has no obvious effect on the prevention of diarrhea. Combining probiotics and improving the ability of probiotics to respond is the focus of attention. © 2023. The Author(s).

BACKGROUND: Halitosis is defined as a foul odour emitted from the oral cavity. Many interventions have been used to control halitosis from mouthwashes to chewing gums. Probiotics have been reported as an alternative method to alleviate halitosis. OBJECTIVE: The present study aimed to investigate the effect of probiotics on halitosis from a time perspective. DESIGN AND METHODS: This is a meta-analysis study performed in indexed databases up to February 2021. Randomised controlled trials that compared the effects of probiotics and placebo on primary outcomes (organoleptic (OLP) scores and volatile sulfur compound (VSC) levels) and secondary outcomes (tongue coating scores (TCS) and plaque index (PI)) were included. Data extraction and quality assessment were conducted independently by two reviewers. Publication bias and leave-one-out analyses were performed. RESULTS: The standardised mean difference (SMD) and 95% CI were calculated to synthesise data. The data were subgrouped and analysed in the short term (≤4 weeks) and long term (>4 weeks) based on the follow-up time. Seven articles were included in this meta-analysis. The primary outcomes, OLP scores (SMD=-0.58; 95% CI -0.87 to -0.30, p<0.0001) and VSC levels (SMD=-0.26; 95% CI -0.51 to -0.01, p=0.04), both decreased significantly in the probiotics group compared with the placebo group in the short term. However, a significant reduction was observed only in OLP scores (SMD=-0.45; 95% CI -0.85 to -0.04, p=0.03) in the long term. No significant differences were observed in secondary outcomes. There was no evidence of publication bias. The leave-one-out analysis confirmed that the pooled estimate was stable. CONCLUSIONS: According to the results of this work, it seems that probiotics (eg, Lactobacillus salivarius, Lactobacillus reuteri, Streptococcus salivarius and Weissella cibaria) may relieve halitosis in the short term (≤4 weeks). The results of the biased assessment, limited data and heterogeneity of the clinical trials included might reduce the reliability of the conclusions. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published

Acute diarrhea is a major cause of morbidity and mortality in children under five. Probiotics are beneficial for treating acute diarrhea in children, but unclear which specific probiotic is the most effective. We performed a Bayesian network meta-analysis to examine the comparative effectiveness of probiotics. By searching EMBASE, PubMed, and the Cochrane Library up to 31 March 2021, randomized clinical trials (RCTs) on probiotics for treating acute diarrhea in children were included. Primary outcomes included the duration of diarrhea and diarrhea lasting ≥2 days, and secondary outcomes included the mean stool frequency on day 2 and duration of hospitalization, fever, and vomiting. We assessed the certainty of the evidence of outcomes according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline. Eighty-four studies with twenty-one different interventions in 13,443 children were included. For the primary outcomes, moderate evidence indicated that, Lactobacillus reuteri [mean difference (MD) = -0.84 day; 95% confidence interval (CI), -1.39, -0.29], Bifidobacterium lactis (MD = -0.98 day; 95%CI, -1.82, -0.14), Saccharomyces boulardii (MD = -1.25 day; 95%CI, -1.59, -0.91), Lactobacillus species (spp.) plus Bifidobacterium spp. plus Saccharomyces spp. (MD = -1.19 day; 95%CI, -1.81, -0.58), and Bacillus spp. plus Enterococcus spp. plus Clostridium spp. (MD = -1.1 day; 95%CI, -1.84, -0.35) significantly reduced the duration of diarrhea when compared with placebo. Saccharomyces boulardii [Odds ratio (OR) = 0.22; 95%CI, 0.11, 0.41] and Lactobacillus reuteri (OR = 0.23; 95%CI, 0.090, 0.60) significantly reduced the risk of diarrhea lasting ≥2 days when compared with placebo or no treatment, with moderate evidence. Among all probiotics, Saccharomyces boulardii may be the most effective in reducing both duration of diarrhea (compared with placebo) and risk of diarrhea lasting ≥2 days (compared with placebo or no treatment), with moderate evidence. To be conclusive, Saccharomyces boulardii may be the most effective probiotic for treating acute diarrhea in children, followed by several other single-strain and multi-strain probiotics.

OBJECTIVE: To investigate evidence for the treatment of childhood colic by supplementing Lactobacillus reuteri in infants breastfed with breast milk. METHODS: The study was conducted according to the PRISMA protocol. The databases used for acquiring data were PubMed and Web of Science, applying MeSH terms and free terms. Meta-analysis was conducted using Stata ™ 12.0. The risk of bias was evaluated by the Review Manager (RevMan) 5.3 tool, and the strength of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Ten clinical trials were included in the review. The administration of L. reuteri (DSM 17938 or ATCC55730) was tested in infants (n = 248) versus the control/placebo group (n = 229). Eight articles were included in the meta-analysis. There was a significant response in reducing crying time (minutes/day) and treatment effectiveness (reduction ≥ 50% in average daily crying time) in the first week (p = 0.001 and p = 0.003, respectively). These results were similar in the second, third weeks (p < 0.001 for both outcomes) and fourth weeks (p<0.001 and p = 0.002, respectively). The risk of bias was low for the majority of the studies. Confidence in evidence was considered very low for crying time and low for effectiveness treatment. CONCLUSIONS: The evidence shows that the administration of Lactobacillus reuteri to babies fed with breast milk reduces the crying time in babies diagnosed with colic. But our confidence in the effect estimate is limited.

In the last decades, the presence of peri-implant diseases (PD) has increased. One of the therapies currently used is probiotics with Lactobacillus reuteri (LR). The aim of this article is to determinate, through a systematic review and meta-analysis, the clinical effectiveness of LR in the treatment of PD. We searched the literature until January 2021, in the biomedical databases: Pubmed, Embase, Scielo, Science Direct, Scopus, SIGLE, LILACS, Google Scholar and Cochrane Central Registry of Clinical Trials. The selection criteria of the studies were: randomized controlled clinical trials, without language and time restriction, reporting the clinical effects (depth to probing, plaque index and bleeding index) of the LR in the PD treatment. The risk of study bias was analyzed through the Cochrane tool for randomized studies using Review Manager software. The search strategy resulted in 6 articles of which four investigated peri-implantitis and three peri-implant mucositis. All studies reported that there was a difference in the depth of the probing in the treatment of PD, in favor of the group using LR, though not always achieving significance. The use of LR can be clinically effective in terms of pocket depth reduction in the treatment of PD. Copyright 2020 Biolife Sas. www.biolifesas.org.

BACKGROUND: Probiotics may be effective in reducing the duration of acute infectious diarrhoea. OBJECTIVES: To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. SEARCH METHODS: We searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews. We included additional studies identified during external review. SELECTION CRITERIA: Randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data. Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea). Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events. MAIN RESULTS: We included 82 studies with a total of 12,127 participants. These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group). No cluster-randomized trials were included. Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested. A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high. Risk of bias was high or unclear in many studies, and there was marked statistical heterogeneity when findings for the primary outcomes were pooled in meta-analysis. Effect size was similar in the sensitivity analysis and marked heterogeneity persisted. Publication bias was demonstrated from funnel plots for the main outcomes. In our main analysis of the primary outcomes in studies at low risk for all indices of risk of bias, no difference w

Background/Objectives: Early-life gut colonization is crucial for immune system development and metabolic programming. Lactobacillus reuteri has been investigated for its capacity to modulate neonatal gut microbiota, but evidence regarding maternal supplementation during lactation remains limited. This study aimed to evaluate the effect of maternal supplementation with L. reuteri SGL 01 on the microbial composition of breast milk and neonatal feces over the first month of life. Methods: This is an exploratory, prospective, open-label randomized clinical trial. Lactating mothers of full-term and exclusively breastfed infants were randomized to receive either daily L. reuteri SGL 01 (1 × 109 CFU) for 30 days or no supplementation. Quantitative real-time PCR was used to assess Bifidobacterium spp., Lactobacillus spp., Clostridium spp., and the Bacteroides fragilis group in maternal milk and neonatal feces at baseline (T0) and after 30 days (T1). Results: Twenty-seven mother-infant dyads completed the study (15 supplemented, 12 controls). No significant changes in breast milk microbiota composition were observed across any of the bacterial taxa following maternal supplementation. In contrast, neonatal fecal samples from the supplemented group showed significant increases in Bifidobacterium spp. (p < 0.001), Lactobacillus spp. (p = 0.029), and Clostridium spp. (p = 0.003) at T1. No significant microbial changes were observed in the control group, except for a slight reduction in Clostridium spp. (p = 0.046). Conclusions: Maternal supplementation with L. reuteri SGL 01 did not modify breast milk microbiota but was associated with a modulation of neonatal gut colonization, including an increased abundance of beneficial taxa such as Bifidobacterium, suggesting potential indirect maternal-to-infant microbial effects.

INTRODUCTION: Pediatric Functional Gastrointestinal Disorders (FGIDs), including infantile colic and constipation, may persist into later childhood and adulthood, sometimes manifesting as functional abdominal pain (FAP). Early exposure to probiotics during critical developmental windows may influence long-term susceptibility to disease. BACKGROUND/OBJECTIVES: Building on our original randomized controlled trial, which demonstrated that Lactobacillus reuteri DSM 17938 reduced acute infantile FGID symptoms, a 10-year follow-up study was performed to evaluate whether this early intervention provided lasting protection against FAP in childhood. METHODS: Two hundred participants from the original RCT cohort completed follow-up assessments at age ten. The primary outcome was the presence of FAP, analyzed according to the original randomization group (probiotic vs placebo). FAP was diagnosed at age 10 using the Rome IV criteria, based on a standardized clinical assessment by a pediatric gastroenterologist who was blinded to the original allocation. RESULTS: FAP was diagnosed in 13/99 (13.1%) children in the probiotic group and 81/101 (80.2%) in the placebo group, corresponding to an absolute risk reduction of 67.1% (95% CI 56.8-77.3) and a relative risk of 0.16 (95% CI 0.10-0.27) (p < 0.001). CONCLUSIONS: Early supplementation with L. reuteri DSM 17938 was associated with a markedly lower prevalence of FAP at age 10. However, the long-term follow-up was observational and characterized by a 57.2% attrition rate. In addition, longitudinal data on potential confounders were unavailable; therefore, the findings should be interpreted as an association rather than proof of causality.

PURPOSE: Infantile colic is increasingly linked to gut microbiota alterations and immune dysregulation, characterized by an imbalance between pro-inflammatory and regulatory pathways. While Lactobacillus reuteri DSM17938 reduces crying time in colicky infants, its immunological mechanisms remain unclear. This study investigated the modulation of type II interferon-stimulated genes (ISGs) in the oral mucosa of colicky infants treated with L. reuteri LMG P-27481 to better understand its impact on mucosal and systemic immunity. PATIENTS AND METHODS: Infants with colic were randomized to receive L. reuteri LMG P-27481 or placebo. Type II interferon signature analysis was performed using Real-Time PCR to quantify ISG expression in the oral mucosa. The genes analysed included CXCL9, IDO1, HLA-DRA, STAT1, and CXCL10. FABP4 was used to confirm treatment-related changes, and expression was compared between groups. RESULTS: L. reuteri administration significantly upregulated CXCL9, IDO1, and HLA-DRA compared to placebo. CXCL9 is involved in immune cell recruitment, suggesting enhanced local immune surveillance. IDO1 upregulation indicates a shift towards immune tolerance through tryptophan metabolism, potentially reducing mucosal hyperreactivity. Increased HLA-DRA expression implies improved antigen presentation capacity, contributing to balanced immune regulation. These findings suggest that L. reuteri modulates mucosal immunity beyond the gastrointestinal tract. CONCLUSION: L. reuteri LMG P-27481 influences immune gene expression in the oral mucosa of colicky infants, supporting its role in promoting immune homeostasis. This immunomodulatory effect may complement its known action on gut microbiota, offering new therapeutic perspectives for infant colic and other pediatric inflammatory conditions. Further research is needed to assess the strain-specificity of these effects and their long-term implications.

Peri-implantitis is a biofilm-induced inflammatory disease that compromises peri-implant tissues, adversely affecting human health and implant survival. As an infectious disease, its management through mechanical debridement alone is often limited by persistent microbial burden. Adjunctive probiotic therapy, grounded in contemporary medicine, has therefore been proposed to improve peri-implant health and oral wellbeing, with potential relevance to broader public health outcomes. The aim of the study was to evaluate the clinical and microbiological effects of subgingival probiotic delivery as an adjunct to mechanical debridement in the non-surgical management of peri-implantitis. A prospective clinical study was conducted involving 52 systemically and periodontally healthy individuals aged 30-60 years with peri-implantitis. Participants were randomly divided into two groups (n = 26 each). Group 1 received mechanical debridement alone, while Group 2 received mechanical debridement combined with subgingival application of Lactobacillus reuteri probiotic. Clinical parameters (PI, GI, PPD, and CAL) and Porphyromonas gingivalis levels were assessed at baseline and three months. RT-PCR was used for microbiological evaluation. Data were analyzed using paired and independent t-tests, with P < 0.05 considered significant. Both groups showed significant intra-group improvements in clinical and microbiological parameters (P < 0.05). However, Group 2 exhibited significantly greater reductions in PI, GI, PPD, CAL, and P. gingivalis levels compared with Group 1 (P = 0.00), demonstrating the superior effectiveness of probiotic therapy. Adjunctive probiotic therapy significantly improves clinical outcomes and reduces microbial load in peri-implantitis patients, offering a beneficial addition to mechanical debridement.

PURPOSE: This randomized, double-blind, placebo-controlled trial evaluated the clinical efficacy of Lactobacillus reuteri in reducing gingival inflammation and alveolar bone loss in periodontitis by modulating endoplasmic reticulum (ER) stress. MATERIALS AND METHODS: A total of 120 patients (aged 22-47 years) with periodontitis (n = 84) or gingivitis (n = 36) were allocated to receive either L. reuteri (1×10⁹ CFU/day, n = 60) or placebo (n = 60) for 8 weeks. Primary outcomes included ER stress markers (GRP78/CHOP), while secondary outcomes comprised probing depth (PD), clinical attachment level (CAL), inflammatory biomarkers (TNF-α, IL-6, CRP), and radiographic alveolar bone loss (Moffat grading). Statistical analyses utilized ANOVA, Welch's t-test, and ANCOVA, with significance at p 0.05. RESULTS: The L. reuteri group exhibited statistically significant reductions in TNF-α (30.01 ± 5.15 vs 16.57 ± 3.88 pg/ml, -45.3%, p 0.05), IL-6 (25.84 ± 3.11 vs 14.35 ± 2.16 pg/ml, -45.2%, p 0.05), and CRP (6.41 ± 1.18 vs 2.68 ± 1.04 mg/L, -57.8%, p 0.05) compared to placebo. Gingival pain (VAS) decreased by 48.5% (5.22 ± 0.51 to 2.69 ± 0.20, p 0.001). ER stress markers GRP78 and CHOP declined by 37.6% (p 0.01) and 35.2% (p 0.01), respectively. PD improved by 35.8% (4.92 ± 1.13 vs 3.12 ± 0.37 mm, p 0.05), with 68.3% of patients achieving ≥2 mm PD reduction (vs 13.3% in controls, p 0.001). Radiographic bone loss improved to mild Moffat grades in 66.7% of test patients (vs 33.3% in controls, p 0.001). CONCLUSIONS: L. reuteri statistically significantly alleviates periodontitis by inhibiting ER stress and inflammatory pathways, demonstrating clinically meaningful reductions in PD, CAL, and alveolar bone loss. These findings underscore its therapeutic potential as an adjunctive intervention.

BACKGROUND: Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes. MATERIALS AND METHODS: We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing. RESULTS: A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental L. reuteri and only at the 1-month post-treatment interval. L. reuteri failed to colonize for long-term the gut, and challenge with L. reuteri failed to alter alpha-diversity (Shannon index) or beta-diversity (community ordination) metrics at any time point. Machine learning (PLS-DA) analysis identified the presence of L. reuteri as the most distinguishing feature at 1 month. No other taxa showed a significant difference between groups. CONCLUSION: Short-term administration of pantoprazole and L. reuteri had no lasting effects on gut microbial composition. While L. reuteri transiently bloomed during supplementation, the overall gut microbiota showed resilience, returning to baseline shortly after therapy. TRIAL REGISTRATION: Identifier: NCT03404440. © 2025 The Author(s). Helicobacter published by John Wiley & Sons Ltd.

BACKGROUND: This study aimed to evaluate the effectiveness of combining Lactobacillus reuteri with racecadotril in treating pediatric rotavirus enteritis, focusing on its impact on intestinal mucosa and immune function. METHODOLOGY: Eighty-five children diagnosed with pediatric rotavirus enteritis were randomly divided into two groups: the control group (43 cases) receiving racecadotril alone and the observation group (42 cases) treated with both Lactobacillus reuteri and racecadotril. Evaluation of the RV conversion rate and treatment efficacy was conducted at 3d, 5d, and 7d post-treatment. The study also assessed changes in intestinal mucosal barrier function, immune response, and intestinal microbiota. RESULTS: The observation group exhibited significantly higher RV conversion rates at 3d, 5d, and 7d post-treatment compared to the control group (P<0.05), reaching 61.90%, 76.19%, and 92.86%, respectively. Following treatment, the observation group showed improvements in mucosal barrier function, increased CD4+ levels, decreased AGEs, D-lactic acid, endotoxins, and CD8+ levels. There were notable changes in intestinal microbiota, with elevated Lactobacillus and Bifidobacterium levels and decreased Escherichia coli. CONCLUSIONS: Combining Lactobacillus reuteri and racecadotril in treating pediatric rotavirus enteritis demonstrated efficacy in regulating intestinal microbiota, alleviating mucosal barrier dysfunction, improving immune function, and enhancing treatment effectiveness. © 2025 He Z et al.

Lactobacillus reuteri DSM 17938 (L. reuteri) has been recommended for treating acute diarrhoea; however, literature data about its efficacy are scarce and controversial. This study investigated the effectiveness of L. reuteri supplementation on the treatment outcome of children with acute diarrhoea. A randomized double-blind controlled trial was conducted in children with acute diarrhoea who attended the outpatient clinic of Srinakharinwirot University Hospital, Thailand. Eligible children were randomly allocated to receive either L. reuteri 1 × 108 colony-forming units or a placebo for 5 days. The primary outcome was the time diarrhoea was resolved. Of the 48 participants (23 in L. reuteri and 25 in the placebo group), 29 (60.4%) were male and the mean age (range) was 12.3 months (1-26 months). The median time for diarrhoea to be resolved was significantly shorter in the L. reuteri group compared to the control (48 and 60 h, respectively, P-value = .042). The percentage of participants who recovered within 48 h was significantly higher in the L. reuteri group (65.2%) compared to the control group (36.0%) [relative risk (RR) 3.33, 95% confidence interval (CI) 1.02-10.89, P-value = .043]. The percentage of participants who recovered from diarrhoea within 72 h was 87.0% and 60%, respectively, [RR 4.44, 95% CI 1.04-19.0, P-value = .036]. No persistent diarrhoea or severe adverse effects were observed in both groups.The use of L. reuteri DSM 17938 as an adjunct therapy led to a significantly shorter duration of diarrhoea in children with acute diarrhoea. © The Author(s) [2025]. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

BACKGROUND: This study aimed to evaluate the clinical efficacy of probiotic-based interventions in modulating the inflammatory response of periapical tissues and maintaining alveolar bone homeostasis following oral alveolar surgery. METHOD: In this open-label, nonblinded trial, 80 patients undergoing alveolar surgery were randomised into an experimental group (n = 40) receiving postoperative Lactobacillus reuteri DSM 17938 probiotics (1010 CFU/d) and a control group (n = 40) receiving standard care. Alveolar bone density was measured via cone-beam computed tomography (CBCT) at 1, 3, and 5 months postsurgery. Oral microbial diversity (16S rRNA sequencing) and inflammatory markers (IL-1β, TNF-α, IL-6) were analysed at 3 months. RESULT: The experimental group demonstrated a 3.8% higher bone density than controls at all follow-ups (P < .05), alongside a 15.2% increase in microbial diversity (Shannon index, P < .05). Proinflammatory cytokines were significantly reduced (IL-1β: -18.5%; TNF-α: -22.1%; IL-6: -14.7%, P < .05). While the bone density improvement was modest, its statistical significance suggests potential clinical relevance for osseointegration. Probiotic supplementation attenuated inflammation and enhanced alveolar bone stability postsurgery. However, the nonblinded design limits generalizability. CONCLUSION: Probiotic-based interventions with Lactobacillus reuteri effectively modulated the inflammatory response and enhanced alveolar bone homeostasis postalveolar surgery in this cohort. While promising, future double-blind trials with larger cohorts are needed to confirm these findings and explore broader translational applications in bone regeneration strategies.

OBJECTIVE: Cystic fibrosis (CF) is a fatal hereditary disorder that leads to respiratory infections and gastrointestinal inflammation with possible association with intestinal dysbiosis. The present study was conducted with the aim of investigating the effects of probiotic consumption in improving pulmonary, gastrointestinal, and growth symptoms in patients with CF. MATERIALS AND METHODS: In this double-blind randomized clinical trial, 110 CF patients were examined. Patients were divided into two equal groups of 55 subjects. Patients in the probiotic group consumed Lactobacillus reuteri at the rate of 108 CFU/d for one month, and the control group received a placebo. Then, pulmonary, gastrointestinal, and growth-related outcomes as well as quality of life were assessed after one month of intervention as well as at three-month follow-up. RESULTS: The results of our study showed that in both intervention and control groups, weight increases significantly after 12 weeks (P = 0.01). However, no remarkable difference was reported between the two groups after 12 weeks (P = 0.09). In addition, no significant changes were observed between the two groups after 4 and 12 weeks regarding BMI and FEV1. Based on the findings, the score of the CFQ questionnaire in the intervention group increased significantly in the 4th and 12th week. No significant differences were observed between the two groups in terms of factors related to lung function or exacerbations after 12 weeks.The only notable effect reported was related to pain attacks in the probiotic group compared to the placebo group after 4 weeks (P = 0.02). CONCLUSION: In general, treatment with probiotics improved the quality of life in patients with CF. However, no significant effect was observed on pulmonary, gastrointestinal, and growth-related outcomes. TRIAL REGISTRATION: This study was retrospectively registered IRCT registration number: IRCT20240105060622N1 (Registration date: 2024-08-16). © 2025. The Author(s).

Antibiotic resistance is one of the world's greatest public health challenges and adjunct probiotic therapies are strategies that could lessen this burden. Clostridioides difficile infection (CDI) is a prime example where adjunct probiotic therapies could decrease disease incidence through prevention. Human-derived Lactobacillus reuteri is a probiotic that produces the antimicrobial compound reuterin known to prevent C. difficile colonization of antibiotic-treated fecal microbial communities. However, the mechanism of inhibition is unclear. We show that reuterin inhibits C. difficile outgrowth from spores and vegetative cell growth, however, no effect on C. difficile germination or sporulation was observed. Consistent with published studies, we found that exposure to reuterin stimulated reactive oxygen species (ROS) in C. difficile, resulting in a concentration-dependent reduction in cell viability that was rescued by the antioxidant glutathione. Sublethal concentrations of reuterin enhanced the susceptibility of vegetative C. difficile to vancomycin and metronidazole treatment and reduced toxin synthesis by C. difficile. We also demonstrate that reuterin is protective against C. difficile toxin-mediated cellular damage in the human intestinal enteroid model. Overall, our results indicate that ROS are essential mediators of reuterin activity and show that reuterin production by L. reuteri is compatible as a therapeutic in a clinically relevant model.

Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF-α)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3 alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin expression was analysed by immunofluorescence; scratch test and trans-epithelial electric resistance test were performed to measure wound healing; adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC) bacteria were made; mRNA expression of TNF-α, interleukin (IL)-8 and vitamin D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight, clinical score, histological score and large intestine weight and length were estimated; mRNA expression of TNF-α, IL-1β, IL-6, IL-10 by quantitative PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria and TNF-α and IL-8 mRNA expression and increases VDR expression. In vivo: KLD significantly improves body weight, clinical score, histological score and large intestine length of mice with DSS-induced colitis and reduces TNF-α, IL-1β and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has significant effects on the intestinal mucosa, strongly decreasing inflammation, increasing epithelial restitution and reducing pathogenicity of harmful commensal bacteria.

Orally administered probiotics change gut microbiota composition and enzyme activities. Thus, coadministration of probiotics with drugs may lead to changes in the pharmacokinetic parameters of the drugs. In this study, we investigated the pharmacokinetics of acetaminophen in mice treated with probiotics. Oral administration of probiotics changed the gut microbiota composition in the mice. Of these probiotics, Lactobacillus reuteri K8 increased the numbers of clostridia, bifidobacteria, and enterococci, and Lactobacillus rhamnosus K9 decreased the number of bifidobacteria, determined by culturing in selective media. Next, we performed a pharmacokinetic study of acetaminophen in mice orally treated with K8 and K9 for 3 days. Treatment with K8 reduced the area under the curve (AUC) of orally administered acetaminophen to 68.4% compared with normal control mice, whereas K9 did not affect the AUC of acetaminophen. Oral administration to mice of K8, which degraded acetaminophen, increased the degradation of acetaminophen by gut microbiota, whereas K9 treatment did not affect it. Treatment with K8 increased the number of L. reuteri adhered in the upper small intestine, whereas the number of L. rhamnosus was not affected by treatment with K8 or K9. K8 increased the number of cyanobacteria, whereas K9 increased the number of deferribacteres. These results suggest that the intake of probiotics may make the absorption of orally administered drugs fluctuate through the disturbance of gut microbiota-mediated drug metabolism and that the subsequent impact on microbiota metabolism could result in altered systemic concentrations of the intact drug.

Reuterin (β-hydroxypropionialdehyde) is a broad-spectrum antimicrobial substance produced by some strains of Lactobacillus reuteri during anaerobic fermentation of glycerol. Some of these strains are able to survive and produce reuterin in cheese and yogurt when added as adjuncts to the starter. Similarly, in fermented dairy foods, other inhibitory compounds such as lactic acid and diacetyl are produced during fermentation. In this work, we studied the combined effect of reuterin and diacetyl under different pH conditions against Escherichia coli O157:H7, Salmonella Enteritidis, and Listeria monocytogenes. Results from agar spot assays showed that the antimicrobial activity of reuterin-producing strains against the gram-negative bacteria tested was enhanced as the concentration of diacetyl increased to 50 mg/kg, and was higher under acidic conditions (pH 5.0) for the 3 pathogenic strains. The combination of reuterin and diacetyl had an additive effect against L. monocytogenes only at diacetyl concentrations of 50 mg/kg and pH 5.0. In addition, growth kinetics studies showed that the combination of 1 activity unit (AU)/mL of reuterin with 100mg/kg diacetyl increased the lag time of the 3 pathogens. In milk, synergistic antimicrobial activity was observed with the combination of 1 AU/mL reuterin and 50 or 100 mg/kg of diacetyl on the gram-negative strains tested, and with 1 AU/mL reuterin and 100 mg/kg of diacetyl on L. monocytogenes. The greatest inhibition of the 3 pathogens was achieved in acidified milk at pH 5.0 with reuterin (1 AU/mL) and diacetyl (100 mg/kg). Based on these results, the combination of reuterin and diacetyl in acidified dairy products could be a promising strategy to control food pathogens in these products.

Three phenyl derivatives of butyrate, 2-phenylbutyrate (2-PB), 3-phenylbutyrate (3-PB) and 4-phenylbutyrate (4-PB), were evaluated in terms of their antibacterial and cytotoxic activities. Our results indicated that PBs demonstrated specific inhibitory activity against Helicobacter pylori and Escherichia coli but did not influence the growth of Bifidobacterium bifidium and Lactobacillus reuteri. PBs also exhibited synergistic effects on H. pylori ATCC 43504 especially at pH 5.5. In the protein expression profiles in H. pylori treated by phenylbutyrates, we also found that three protein spots identified as oxidative stress-related proteins were significantly up-regulated, confirming the response of H. pylori when exposed to PBs. Due to their antibacterial activities and low or slight cytotoxicities, PBs are potential candidates for the treatment of H. pylori infection. This is the first study to discover the antibiotic effects of 2-PB, 3-PB and 4-PB (Buphenyl).

Background: Helicobacter pylori (H. pylori) infection is important risk factors for chronic gastritis, peptic ulcer and gastric cancer. Bismuth-containing quadruple therapy has recently been the first-line regimen recommended in many European countries but has limited efficacy in ASEAN especially Thailand. This study was aim to evaluate efficacy of high dose PPI Bismuth-containing quadruple therapy with probiotics supplement for H. pylori eradication. Methods: In this double-blind randomized placebo-controlled study, H. pylori infected patients were randomized to receive 7-or 14-day high dose PPI- bismuth-containing quadruple therapy with or without probiotics supplement. Probiotic was 37.5 mg Lactobacillus reuteri (Biogaia®) in tablet twice daily. CYP2C19 genotyping and antibiotic susceptibility tests were also done. H. pylori eradication was defined as a negative 13C-urea breath test at least 4 weeks after treatment. Results: 100 subjects were enrolled (72 females, 28 males, mean age=54 years). Antibiotic resistance was 15.6% for clarithromycin, 34.1% for metronidazole. CYP2C19 genotyping was performed in both group and revealed 13%, 50% and 37% for poor, intermediate and rapid metabolizers, respectively. Overall eradication rates of 7-day and 14-day regimens with probiotic were 68% and 96%; P value=0.027. The eradication rate for all patients with poor and rapid metabolizers were 100% with 14-day regimen. 14-day regimen with probiotics can provide 100% eradication with clarithromycin resistance, metronidazole resistance or dual clarithromycin and metronidazole resistance group. Furthermore, the incidence of nausea and vomiting, abdominal discomfort, and bitter taste were significantly lower in patients with probiotics group compared with placebo (6%vs.26%, P=0.002,OR=0.126,95% CI=0.03-0.53; 4%vs.18.0%, P=0.017, OR= 0.155,95% CI=0.03-0.81 and 4%vs.26%, P= 0.001,OR= 0.08, 95%CI= 0.016-0.41, respectively). Conclusions: The 14-day high dose PPI- bismuth-containing quadruple therapy with probiotic can provide an excellent cure rate for H. pylori infection as first line treatment irrespective of CYP2C19 and antibiotic resistance pattern. Adding probiotic also signi

Probiotics and milk calcium may increase resistance to intestinal infection, but their effect on growth and iron and zinc status of Indonesian children is uncertain. We investigated the hypotheses that cow milk with added probiotics would improve growth and iron and zinc status of Indonesian children, whereas milk calcium alone would improve growth but reduce iron and zinc status. A 6-mo randomized trial was conducted in low-socioeconomic urban communities of Jakarta. Healthy children (n = 494) were randomly assigned to receive low-lactose milk with a low calcium content of ∼50 mg/d (LC; n = 124), a regular calcium content of ∼440 mg/d (RC group; n = 126), regular calcium with 5 × 10(8) CFU/d Lactobacillus casei CRL 431 (casei; n = 120), or regular calcium with 5 × 10(8) CFU/d Lactobacillus reuteri DSM 17938 (reuteri; n = 124). Growth, anemia, and iron and zinc status were assessed before and after the intervention. Compared with the RC group, the reuteri group had significantly greater weight gain [0.22 (95% CI: 0.02, 0.42) kg], weight-for-age Z-score (WAZ) changes [0.09 (95% CI: 0.01, 0.17)], and monthly weight [0.03 (95% CI: 0.002, 0.05) kg/mo] and height [0.03 (95% CI: 0.01, 0.05) cm/mo] velocities. Casei significantly increased monthly weight velocity [0.03 (95% CI: 0.001, 0.05) kg/mo], but not height. However, the changes in underweight, stunting, anemia prevalence, and iron and zinc status were similar between groups. In conclusion, L. reuteri DSM 17938 modestly improved growth by increasing weight gain, WAZ changes, and weight and height velocity, whereas L. casei CRL 431 modestly improved weight velocity. Independent from probiotics supplementation, regular milk calcium did not affect growth or iron and zinc status.

OBJECTIVE: To investigate the effects of calcium and probiotics on the incidence and duration of acute diarrhea and acute respiratory tract infections (ARTIs) in low-socioeconomic communities of Jakarta, Indonesia. METHODS: We conducted a 6-month, double-blind, placebo-controlled study in 494 healthy children aged 1 to 6 years who received low-lactose milk with low calcium content (LC; ∼50 mg/day; n = 124), regular calcium content (RC; ∼440 mg/day; n = 126), RC with 5.10(8) colony-forming units per day of Lactobacillus casei CRL431 (casei; n = 120), or RC with 5.10(8) colony-forming units per day of Lactobacillus reuteri DSM17938 (reuteri; n = 124). Number and duration of diarrhea and ARTIs episodes were primary and secondary outcomes, respectively. RESULTS: Incidence of World Health Organization-defined diarrhea (≥3 loose/liquid stools in 24 hours) was not significantly different between RC and LC (relative risk [RR]: 0.99 [95% confidence interval (CI): 0.62-1.58]), between casei and RC (RR: 1.21 [95% CI: 0.76-1.92]), or between reuteri and RC (RR: 0.76 [95% CI: 0.46-1.25]) groups. Incidence of all reported diarrhea (≥2 loose/liquid stools in 24 hours) was significantly lower in the reuteri versus RC group (RR: 0.68 [95% CI: 0.46-0.99]). Irrespective of the definition used, reuteri significantly reduced diarrhea incidence in children with lower nutritional status (below-median height-and-weight-for-age z score). None of the interventions affected ARTIs. CONCLUSIONS: RC milk, alone or with L casei, did not reduce diarrhea or ARTIs in Indonesian children. L reuteri may prevent diarrhea, especially in children with lower nutritional status.

Background/Objectives: Increasing evidence implicates the microbiome-gut-brain axis in Autism Spectrum Disorder (ASD) pathophysiology, prompting interest in probiotics as a therapeutic strategy, although findings remain inconsistent. This systematic review aimed to evaluate the clinical efficacy of probiotic supplementation on core ASD symptoms, examine the outcome measures used, and provide insights into optimal probiotic interventions. Methods: This review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, Ovid, ProQuest, and Wiley Online Library were searched for studies published between January 2015 and July 2025. Randomized, non-randomized, and open-label clinical studies evaluating oral probiotic supplementation in children and adolescents with ASD were included. Outcomes assessed core symptom domains using validated instruments. Study selection, data extraction, and risk-of-bias assessment (RoB 2 and ROBINS-I) were performed independently by multiple reviewers. Due to methodological heterogeneity, the findings were synthesized narratively. Results: Fourteen studies involving 924 children and adolescents with ASD across seven countries or regions were included, of which ten were randomized controlled trials. Eight studies reported significant improvement in core ASD symptoms, predominantly within the social and communication domain. The most frequently used assessment tools were the Social Responsiveness Scale (SRS), Autism Treatment Evaluation Checklist (ATEC), and Autism Diagnostic Observation Schedule (ADOS). Lactobacillus reuteri supplementation for at least three months was consistently associated with improvement in social behavior. Conclusions: L. reuteri supplementation possibly improves social and communication function in children with ASD. However, there is limited high-quality evidence on this. Evidence for other core domains remains limited and inconsistent, highlighting the need for well-designed, multicenter trials using standardized outcome measures and strain-specific hypotheses.

BACKGROUND: Osteoporosis is a major global health concern characterized by reduced bone mass and structural deterioration. The RANK/RANKL/OPG signaling pathway plays a pivotal role in bone remodeling, particularly in osteoclastogenesis. Emerging evidence suggests that probiotics may modulate this pathway through the gut-bone axis, offering potential therapeutic benefits for bone loss. OBJECTIVE: This systematic review aims to evaluate the effects of probiotic supplementation on Receptor activator of nuclear factor kappa-Β ligand (RANKL) in animal and human interventional studies related to osteoporotic conditions. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar databases up to June 2025. Original interventional studies published in English, including both animal and human models, were selected according to predefined inclusion and exclusion criteria. The selection process followed PRISMA guidelines. Studies were assessed for quality by independent reviewers, and relevant data were extracted for synthesis. RESULTS: A total of 24 studies met the inclusion criteria, most using ovariectomized rodent models and two randomized controlled trials in postmenopausal women. Several probiotic strains-particularly Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus casei, and Bifidobacterium longum-significantly reduced RANKL expression in animal models, whereas human trials yielded limited or no effect on RANKL despite improvements in other bone turnover markers. CONCLUSION: Probiotic interventions appear to exert beneficial effects on bone metabolism by modulating RANKL, particularly in estrogen-deficiency-induced osteoporosis models. However, findings from human trials remain limited and inconsistent. Further high-quality RCTs are warranted to confirm these effects and determine optimal strains, dosages, and treatment durations.