Lactobacillus rhamnosus GG

Background and Objectives: Cystic fibrosis (CF), caused by CFTR gene mutations, primarily affects the respiratory and gastrointestinal systems. Microbiota modulation through probiotics, prebiotics, or synbiotics may help restore microbial diversity and reduce inflammation. This study aimed to evaluate their efficacy in CF. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) published between 2000 and 2024 was conducted in Cochrane, ScienceDirect, Web of Science, LILAC, BMC, PubMed, and SCOPUS following PRISMA guidelines. Methodological quality was assessed using the Jadad scale, and RevMan 5.4® estimated effects on pulmonary function (FEV1), exacerbations, hospitalizations, quality of life, and inflammatory markers. Results: Thirteen RCTs (n = 552), mostly in pediatric populations, were included. Most examined probiotics (e.g., Lactobacillus rhamnosus GG, L. reuteri), while four used synbiotics. Several studies reported reduced fecal calprotectin and proinflammatory interleukins (e.g., IL-6, IL-8), suggesting an anti-inflammatory effect. However, no significant differences were observed regarding hospitalizations or quality of life. Additionally, none of the studies documented serious adverse events associated with the intervention. The meta-analysis showed no significant decrease in exacerbations (RR = 0.81; 95% CI = 0.48-1.37; p = 0.43) or improvements in FEV1 (MD = 4.7; 95% CI = -5.4 to 14.8; p = 0.37), even in subgroup analyses. Sensitivity analyses did not modify the effect of the intervention on pulmonary function or exacerbation frequency, supporting the robustness of the findings. Conclusions: Current evidence suggests that probiotics or synbiotics yield inconsistent clinical benefits in CF, although some reduction in inflammatory markers may occur. Larger, multicenter RCTs with longer follow-up are needed for clearer conclusions. Until more definitive evidence is available, these supplements should be considered experimental adjuncts rather than standard interventions for CF management.

Lactobacillus rhamnosus GG (LGG) is a widely used and extensively researched probiotic. Probiotic effects are considered to be strain specific. We aimed to comprehensively assess the strain-specific effects of LGG in preterm infants. A systematic review of RCTs and non-RCTs to evaluate the effect of LGG in preterm infants. We followed the Cochrane methodology, and preferred reporting items for systematic reviews (PRISMA) statement for conducting and reporting this review. We searched the Cochrane central register of controlled trials, PubMed, EMBASE and CINAHL databases till December 2023. The review was registered in PROSPERO 2022 CRD42022324933. Meta-analysis of data from RCTs that used LGG as the sole probiotic showed significantly lower risk of NEC ≥Stage II [5 RCTs, n = 851, RR:0.50 (95% CI: 0.26, 0.93), P = 0.03] in the LGG group. There was no significant difference in the risk of LOS [7 RCTs, n = 1037, RR:1.08 (95% CI 0.84, 1.39), P = 0.55], mortality [3 RCTs, n = 207, RR: 0.99 (95% CI: 0.42, 2.33), P = 0.99], time to reach full feeds [2 RCTs, n = 19, SMD = 0.11 days (95% CI: -0.22, 0.45), P = 0.51] and duration of hospital stay [3 RCTs, n = 293, SMD: -0.14 days (95% CI: -0.37 to 0.09), P = 0.23]. Meta-analysis of data from non-RCTs showed no significant effect of LGG on NEC, LOS, and mortality. RCTs showed beneficial effects of LGG when used as the sole probiotic in reducing the risk of NEC, whereas observational studies did not. Strain-specific systematic review of LGG provides important data for guiding research and clinical practice. © 2024. The Author(s), under exclusive licence to Springer Nature Limited.

BACKGROUND: Functional abdominal pain is pain occurring in the abdomen that cannot be fully explained by another medical condition and is common in children. It has been hypothesised that the use of micro-organisms, such as probiotics and synbiotics (a mixture of probiotics and prebiotics), might change the composition of bacterial colonies in the bowel and reduce inflammation, as well as promote normal gut physiology and reduce functional symptoms. OBJECTIVES: To assess the efficacy and safety of probiotics in the treatment of functional abdominal pain disorders in children. SEARCH METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and two clinical trials registers from inception to October 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compare probiotic preparations (including synbiotics) to placebo, no treatment or any other interventional preparation in patients aged between 4 and 18 years of age with a diagnosis of functional abdominal pain disorder according to the Rome II, Rome III or Rome IV criteria. DATA COLLECTION AND ANALYSIS: The primary outcomes were treatment success as defined by the primary studies, complete resolution of pain, improvement in the severity of pain and improvement in the frequency of pain. Secondary outcomes included serious adverse events, withdrawal due to adverse events, adverse events, school performance or change in school performance or attendance, social and psychological functioning or change in social and psychological functioning, and quality of life or change in quality life measured using any validated scoring tool. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI. MAIN RESULTS: We included 18 RCTs assessing the effectiveness of probiotics and synbiotics in reducing the severity and frequency of pain, involving a total of 1309 patients. Probiotics may achieve more treatment success when compared with placebo at the end of the treatment, with 50% success in the probiotic group versus 33% success in the p

OBJECTIVES: To determine the safety and efficacy of probiotics or synbiotics on morbidity and mortality in critically ill adults and children. DATA SOURCES: We searched MEDLINE, EMBASE, CENTRAL, and unpublished sources from inception to May 4, 2021. STUDY SELECTION: We performed a systematic search for randomized controlled trials (RCTs) that compared enteral probiotics or synbiotics to placebo or no treatment in critically ill patients. We screened studies independently and in duplicate. DATA EXTRACTION: Independent reviewers extracted data in duplicate. A random-effects model was used to pool data. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Sixty-five RCTs enrolled 8,483 patients. Probiotics may reduce ventilator-associated pneumonia (VAP) (relative risk [RR], 0.72; 95% CI, 0.59 to 0.89 and risk difference [RD], 6.9% reduction; 95% CI, 2.7-10.2% fewer; low certainty), healthcare-associated pneumonia (HAP) (RR, 0.70; 95% CI, 0.55-0.89; RD, 5.5% reduction; 95% CI, 8.2-2.0% fewer; low certainty), ICU length of stay (LOS) (mean difference [MD], 1.38 days fewer; 95% CI, 0.57-2.19 d fewer; low certainty), hospital LOS (MD, 2.21 d fewer; 95% CI, 1.18-3.24 d fewer; low certainty), and duration of invasive mechanical ventilation (MD, 2.53 d fewer; 95% CI, 1.31-3.74 d fewer; low certainty). Probiotics probably have no effect on mortality (RR, 0.95; 95% CI, 0.87-1.04 and RD, 1.1% reduction; 95% CI, 2.8% reduction to 0.8% increase; moderate certainty). Post hoc sensitivity analyses without high risk of bias studies negated the effect of probiotics on VAP, HAP, and hospital LOS. CONCLUSIONS: Low certainty RCT evidence suggests that probiotics or synbiotics during critical illness may reduce VAP, HAP, ICU and hospital LOS but probably have no effect on mortality.

BACKGROUND: Atopic dermatitis is the most common chronic skin disease affecting the pediatric population. Probiotics have been proposed to be effective in preventing the development of pediatric atopic dermatitis. Although studies show promise for the use of probiotics, the evidence is still inconclusive due to significant heterogeneity and imprecision. OBJECTIVE: To determine the comparative effectiveness of the different types of probiotic strains in preventing the development of atopic dermatitis among pediatric patients. METHODOLOGY: A systematic search of Cochrane Library, MEDLINE, TRIP Database, and Centre for Research and Dissemination was conducted. Manual search of the reference lists and search for unpublished articles were also done. All randomized controlled trials available from inception until April 12, 2020, on the use of probiotics in the prevention of atopic dermatitis among children were included. The comparator groups considered are other probiotic strains and placebo. The primary outcome of interest was the development of atopic dermatitis. Two authors independently searched for articles, screened the articles for inclusion, appraised the articles using the Cochrane risk of bias tool version 2, and extracted the data. In case of disagreement, the two authors discussed the source of disagreement until consensus was reached. If consensus was not reached, an independent third party reviewer was consulted. Frequentist network meta-analysis was conducted using STATA 14 software. The ranking probabilities and surface under the cumulative ranking curve (SUCRA) values were obtained to determine ranking of the different probiotic strains based on efficacy and safety data. RESULTS: We included 21 original studies represented by 35 records and a total of 5406 children with atopic dermatitis as diagnosed by clinicians or fulfillment of validated diagnostic criteria. All studies were randomized placebo-controlled trials. The top 3 probiotic preparations in terms of efficacy in reducing the risk of atopic dermatitis are Mix8 (Lactobacillus paracasei ST11, Bifidobacterium longum BL999), LP (Lactobacillus paracasei ssp paracasei F19) and Mix3 (Lactobacillus

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

Functional abdominal pain is a very frequent functional gastrointestinal disorder but still without adequate treatment options. Therefore, the main aim of this systematic review and meta-analysis was to evaluate strain-specific probiotic effects on functional abdominal pain in children. This was a systematic review and meta-analysis of randomized controlled trials published in a period up to 1st of April 2020 that analyzed probiotic interventions for pediatric functional abdominal pain. We included 9 randomized controlled trials (a total of 702 children, 506 with functional abdominal pain; 4 to 18 years); 8 studies were available for meta-analysis (a total of 641 children). Lactobacillus rhamnosus GG and Lactobacillus reuteri DSM 17938 were the only two probiotic strains investigated. Significant reduction in pain intensity (6 trials, n = 380, mean difference - 1.24, 95% CI - 2.35 to - 0.13) and increase in number of days without pain (2 trials, n = 101, mean difference 26.42, 95% CI 22.67 to 30.17) were found in children taking L. reuteri DSM 17938. For all other outcomes, there were no significant differences between probiotic and placebo.Conclusion: Based on the available evidence, no firm conclusions can be given; however, L. reuteri was proven to decrease the pain intensity in children with functional abdominal pain. Further trials regarding long-term outcomes, possibly involving longer interventions, are needed. What is Known: • Previously published systematic reviews have suggested that probiotics may have an effect on the pain in children with functional gastrointestinal disorders, but limited data exist on strain-specific effects. What is New: • This systematic review provides evidence on the probiotic use on the strain-specific level. • This systematic review showed that the use of Lactobacillus reuteri DSM 17938 modestly reduces the pain intensity in children with functional abdominal pain.

BACKGROUND: Gestational diabetes mellitus (GDM) is carbohydrate intolerance first recognised during pregnancy and associated with complications for mothers and babies. Probiotics are naturally occurring micro-organisms, which when ingested in adequate amounts, may confer health benefits. Evidence of the role of probiotics as treatment for GDM is limited. OBJECTIVES: To evaluate the safety and effectiveness of probiotics in treating women with GDM on maternal and infant outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (24 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of probiotics versus placebo/standard care for the treatment of GDM. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, checked data accuracy, and assessed risk of bias of included trials. The certainty of evidence for selected maternal and infant/child outcomes was assessed using GRADE. MAIN RESULTS: Nine RCTs (695 pregnant women with GDM) comparing probiotics versus placebo were identified. The overall risk of bias in the nine RCTs was low to unclear and the evidence was downgraded for imprecision due to the small numbers of women participating in the trials. The trials were carried out in hospitals and universities in Iran (seven trials), Thailand (one trial) and Ireland (one trial). All trials compared probiotics with placebo. Maternal outcomes We are uncertain if probiotics have any effect compared with placebo on hypertensive disorders of pregnancy, (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.64 to 3.53; participants = 256; studies = 3; low-certainty evidence) and mode of birth as caesareans (average RR 0.64, 95% CI 0.30 to 1.35; participants = 267; studies = 3; low-certainty evidence) because the certainty of evidence is low and the 95% CIs span possible benefit and possible harm. No trials reported primary outcomes of: mode of birth as vaginal/assisted and subsequent development of type 2 diabetes. We are uncertain if probio

BACKGROUND: The current evidence on the use of probiotics in treating atopic dermatitis is inconclusive. This study determined the comparative effectiveness of the different types of probiotic strains in treating pediatric atopic dermatitis. METHODOLOGY: Systematic and manual search for all randomized controlled trials available from inception until January 31, 2020, was done. Two independent authors conducted the search, screening, appraisal, and data abstraction. Network meta-analysis was conducted using STATA 14 software. RESULTS: Twenty-two studies involving 28 different probiotic strains were included. The top three ranked probiotic strains in terms of efficacy are Mix1 (Bifidobacterium animalis subsp lactis CECT 8145, Bifidobacterium longum CECT 7347, and Lactobacillus casei CECT 9104); Lactobacillus casei DN-114001; and Mix6 (Bifidobacterium bifidum, Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus salivarius). Compared with placebo, Mix1 reduces atopic dermatitis symptoms with high certainty evidence (SMD -1.94, 95% CI -2.65 to -1.24; 47 participants). Mix6 compared with placebo probably reduces atopic dermatitis symptoms based on moderate certainty evidence (SMD -0.85, 95% CI -1.50 to -0.20; 40 participants). Lactobacillus casei DN-114001 compared with placebo may reduce atopic dermatitis symptoms based on low certainty evidence (SMD -1.35, 95% CI -2.04 to -0.65). In terms of safety, the highest ranked strain is Lactobacillus fermentum VRI-003, while the lowest ranked strain is Lactobacillus rhamnosus GG. CONCLUSION: Certain probiotic preparations show benefit in reducing allergic symptoms in pediatric atopic dermatitis. © 2020 EAACI and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BACKGROUND: Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide. In clinical trials, Lactobacillus rhamnosus GG ATCC 53013 (LGG) has been used to treat diarrhea. However, recent randomized controlled trials (RCTs) found no evidence of a beneficial effect of LGG treatment. AIM: To evaluate the efficacy of LGG in treating acute diarrhea in children. METHODS: The EMBASE, MEDLINE, PubMed, Web of Science databases, and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for meta-analyses and RCTs. The Cochrane Review Manager was used to analyze the relevant data. RESULTS: Nineteen RCTs met the inclusion criteria and showed that compared with the control group, LGG administration notably reduced the diarrhea duration [mean difference (MD) -24.02 h, 95% confidence interval (CI) (-36.58, -11.45)]. More effective results were detected at a high dose ≥ 1010 CFU per day [MD -22.56 h, 95%CI (-36.41, -8.72)] vs a lower dose. A similar reduction was found in Asian and European patients [MD -24.42 h, 95%CI (-47.01, -1.82); MD -32.02 h, 95%CI (-49.26, -14.79), respectively]. A reduced duration of diarrhea was confirmed in LGG participants with diarrhea for less than 3 d at enrollment [MD -15.83 h, 95%CI (-20.68, -10.98)]. High-dose LGG effectively reduced the duration of rotavirus-induced diarrhea [MD -31.05 h, 95%CI (-50.31, -11.80)] and the stool number per day [MD -1.08, 95%CI (-1.87, -0.28)]. CONCLUSION: High-dose LGG therapy reduces the duration of diarrhea and the stool number per day. Intervention at the early stage is recommended. Future trials are expected to verify the effectiveness of LGG treatment.

OBJECTIVE: The aim of this study was to examine the prevalence and incidence of diarrhea, diarrhea risk factors, processes of care, and clinical outcomes associated with diarrhea in invasively ventilated patients in the ICU. DESIGN: Bedside nurses prospectively documented each patient's bowel movement (BM) using the Bristol Stool Chart type and number. Research Coordinators collected baseline and daily data evaluating risk factors for diarrhea and patient outcomes. The diarrhea definition was the World Health Organization definition of ≥3 loose or watery BMs (Bristol type 6 or 7) per day. We used Cox proportional hazards regression to evaluate risk factors and the association with the risk of death in the ICU. SETTING: Forty-four ICUs in Canada, the United States, and Saudi Arabia. PATIENTS: All 2,650 invasively ventilated critically ill patients were enrolled in this preplanned secondary analysis of a randomized trial that evaluated the probiotic Lactobacillus rhamnosus GG on infectious outcomes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,650 patients, the mean age (sd) was 59.8 (16.5) years, with an Acute Physiology and Chronic Health Evaluation II Score of 22.0 (7.8); 61.2% received inotropes/vasopressors on study day 1. Diarrhea occurred among 60.4% of patients and on 18.2% of ICU study days. Independent risk factors for diarrhea were a history of Clostridioides difficile infection, laxatives, and antibiotic use. Adjusted for these factors, enteral nutrition, particularly with moderate-high-protein content, also increased the risk of diarrhea. Univariable analysis suggested that diarrhea was associated with C. difficile testing, fecal management device insertion, and increased length of ICU and hospital stay. After adjusting for illness severity, mechanical ventilation, inotropes/vasopressors, renal replacement therapy, and severe infections, diarrhea was not associated with an increased risk of death. CONCLUSIONS: Diarrhea is common among invasively ventilated patients. Risk factors include a history of C. difficile, use of antibiotics, laxatives, and enteral nutrition, particularly moderate-high-protein composition feeds.

Background: the aim of this randomized placebo-controlled study was to investigate the effect of probiotics mainly on plasma lipids, homocysteine levels, glycemic biomarkers and inflammatory marker in people with hyperlipidemia, compared to a placebo. Methods: a randomized, double-blind placebo-controlled study was completed with a total of 51 men and women who have diagnosed with hyperlipidemia. The three study interventions were: 1) probiotic group I asked to take once a day 1 x 106 colony forming unit (CFU) Lactobacillus rhamnosus GG microorganism (n = 18) capsule; 2) probiotic group II asked to take once a day of a combined Lactobacillus acidophilus 1 x 109 CFU and Bifidobacterium animalis subsp.lactis 1 x 109 CFU probiotic capsule (n = 17); and 3) placebo group: emptied capsule (n = 16), plasma lipids, homocysteine, and glycemic biomarkers were were performed at baseline and week 8. Also, hs-CRP levels was assessed as inflammatory parameter. Results: compared to baseline there was a significant decrease in triglyceride and total cholesterol levels of the both intervention groups compared to the placebo group. Regarding the glycemic biomarkers. both intervention groups significantly alter the HOMA-IR values compared to the placebo group (p < 0.05). When homocysteine values were evaluated. a statistically significant decrease was observed only in the group using the combined strain (p < 0.05). Results demonstrated that regular and strain-specific use of probiotics have effective and favorable consequences on plasma lipids and glycemic biomarkers. Conclusion: probiotics containing Lactobacillus or Bifidobacterium could be effective in hypercholesterolemic patients, reducing serum lipids as well as homocysteine and glycaemia. Publisher: Objetivo: el objetivo de este estudio aleatorizado controlado con placebo fue investigar el efecto de los probióticos principalmente en los lípidos plasmáticos, los niveles de homocisteína, los biomarcadores glucémicos y el marcador inflamatorio en personas con hiperlipidemia, en comparación con un placebo. Métodos: se realizó un estudio doble ciego aleatoria controlado con placebo con un total de 51 hombres y mujeres a quienes

The aim of this study was to obtain insight into the composition and function of the deviant gut microbiome throughout infancy in children born moderately and late preterm and their response to microbiome modulation. We characterized the longitudinal development of the gut microbiome from birth to the age of 12 months by metagenomic sequencing in 43 moderate and late preterm children participating in a randomized, controlled trial (ClinicalTrials.gov/no.NCT00167700) assessing the impact of a probiotic (Lactobacillus rhamnosus GG, ATCC 53,103, currently Lacticaseibacillus rhamnosus GG) and a prebiotic (galacto-oligosaccharide and polydextrose mixture, 1:1) intervention as compared to a placebo administered from 3 to 60 days of life. In addition, 9 full-term, vaginally delivered, breast-fed infants, who remained healthy long-term were included as references. Significant differences in taxonomy, but not in functional potential, were found when comparing the gut microbiome composition of preterm and full-term infants during the first month of life. However, the gut microbiome of preterm infants resembled that of full-term infants by 6 months age. Probiotic and prebiotic treatments were found to mitigate the shift in the microbiome of preterm infants by accelerating Bifidobacteria-dominated gut microbiome in beta diversity analysis. This study provides intriguing information regarding the establishment of the gut microbiome in children born moderately and late preterm, representing the majority of children born preterm. Specific pro- and prebiotics may reverse the proinflammatory gut microbiome composition during the vulnerable period, when the microbiome is low in resilience and susceptible to environmental exposure and simultaneously promotes immunological and metabolic maturation.

INTRODUCTION: We investigated the effect of daily oral Lactobacillus rhamnosus GG (LGG) in reducing liver injury/severity and drinking in patients with alcohol use disorder and moderately severe alcohol-associated hepatitis. METHODS: Forty-six male and female individuals with alcohol use disorder and moderate alcohol-associated hepatitis (12 ≤ model for end-stage liver disease score < 20, aged 21-67 years) received either LGG (n = 24) or placebo (n = 22). Data were collected/assessed at baseline and at 1, 3, and 6 months. RESULTS: LGG treatment was associated with a significant reduction in liver injury after 1 month. Six months of LGG treatment reduced heavy drinking levels to social or abstinence levels. DISCUSSION: LGG treatment was associated with an improvement in both liver injury and drinking.

BACKGROUND: Preterm children with their aberrant gut microbiota and susceptibility to infections and inflammation constitute a considerable target group for probiotic therapy to generate the age-appropriate healthy microbiota. METHODS: 68 preterm neonates were randomized into five intervention groups: Beginning from the median age of 3 days, 13 children received Lactobacillus rhamnosus GG (LGG) directly orally, and 17 via the lactating mother. 14 children received LGG with Bifidobacterium lactis Bb-12 (Bb12) orally, and 10 via the lactating mother. 14 children received placebo. The children's faecal microbiota was assessed at the age of 7 days by 16S rRNA gene sequencing. RESULTS: The gut microbiota compositions of the children directly receiving the probiotic combination (LGG + Bb12) were significantly different from those of the children receiving the other intervention modes or placebo (p = 0.0012; PERMANOVA), the distinction being due to an increase in the relative abundance of Bifidobacterium animalis (P < 0.00010; ANCOM-BC), and the order Lactobacillales (P = 0.020; ANCOM-BC). CONCLUSION: The connection between aberrant primary gut microbiota and a heightened risk of infectious and non-communicable diseases invites effective microbiota modulation. We show that the direct, early, and brief probiotic intervention of LGG + Bb12 109 CFU each, is sufficient to modulate the gut microbiota of the preterm neonate. IMPACT: Preterm children have a higher risk of several health problems partly due to their aberrant gut microbiota. More research is needed to find a safe probiotic intervention to modify the gut microbiota of preterm children. The maternal administration route via breast milk might be safer for the newborn. In our study, the early and direct administration of the probiotic combination Lactobacillus rhamnosus GG with Bifidobacterium lactis Bb-12 increased the proportion of bifidobacteria in the preterm children's gut at the age of 7 days, but the maternal administration route was not as effective. © 2023. The Author(s).

PURPOSE: Recent studies indicate that dysbiosis of gut microbiota and low-grade inflammation are important pathogenic determinants of type two diabetes mellitus (T2DM). The aim of this study is to investigate the effects of Lactobacillus GG on glycemic control, lipid profile, inflammatory parameters, and some gene expression levels in individuals with T2DM. METHODS: In a randomized, placebo-controlled trial, 34 women, aged 30-60 years with T2DM consumed daily probiotics or placebo for 8 weeks. The probiotic group consumed 10 × 109 Cfu/day Lactobacillus rhamnosus GG ATCC 53,103 (LGG), approved by the TR Ministry of Food, Agriculture, and Livestock. Anthropometric measurements, food diary, fasting blood, and fecal samples were taken at baseline and post-treatment. RESULTS: Fasting blood glucose was significantly decreased in probiotic (p = 0.049) and placebo (p = 0.028), but there was no difference between the groups. In the probiotic group, no significant difference was observed in HbA1c, fructosamine, lipid profile, and inflammatory variables compared to baseline. In this group, with LGG supplementation, mucin 2 and 3A (MUC2 and MUC3A) gene expressions increased more than ninefolds (p = 0.046 and p = 0.008, respectively) at post-treatment. Meanwhile, there was no significant change in any of the gene expressions in the placebo group. There was no significant difference in energy, protein, dietary fiber, and cholesterol intakes between placebo and probiotic groups during the study. However, daily fat intake (p = 0.003), body weight (p = 0.014), and body fat (p = 0.015) in the probiotic group were significantly decreased. CONCLUSION: In this study, the effects of a single probiotic strain were investigated for 8 weeks. At the end of the study, although there was no finding that clearly reflected on the glycemic parameters of T2DM, its beneficial effects on the expression of mucin genes, which are responsible for weight loss and protection of intestinal barrier functions, cannot be denied. Further studies are needed to reveal the importance of these findings. CLINICAL TRIAL REGISTRATION: ID: NCT05066152, October 4, 2021 retrospectively registered in ClinicalTrials.

INTRODUCTION: Clostridioides difficile infection (CDI) is a serious complication of critical illness. The objective of the study was to determine its incidence, prevalence, timing, severity, predictors, and outcomes. METHODS: We performed a prospective nested cohort study of CDI within a randomized trial comparing Lactobacillus rhamnosus GG to placebo. We adjudicated cases of CDI using standardized definitions, assessed timing (pre-ICU, in ICU, post-ICU) and severity. We analyzed risk factors and outcomes. RESULTS: Of 2650 patients, 86 were diagnosed with CDI during 90,833 hospital-days (0.95/1000 hospital-days); CDI prevalence was 3.2%. CDI incidence varied in timing; 0.3% patients had CDI pre-ICU, 2.2% in the ICU; an 0.8% developed CDI post-ICU. Relapse or recurrence of CDI was documented in 9.3% patients. Infections were mild/moderate in severity. Complications included septic shock (26.7%), organ failure (16.3%), and toxic megacolon requiring colectomy (1.2%). No risk factors for CDI were identified. CDI was not associated with hospital mortality. The duration of hospital stay was longer for those who had CDI compared those who did not, CONCLUSION: CDI was uncommon, severity was mild to moderate and not associated with mortality however CDI was associated with a longer hospital stay. Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.

AIM: Melatonin seems to have a positive impact on the brain-gut axis and many direct and indirect effects on the gastrointestinal tract. This trial aimed at assessing the efficacy of melatonin combined with Lactobacillus Rhamnosus GG given in the treatment of paediatric patients with functional abdominal pain disorders. METHODS: Forty-two patients aged 4-18 years old who fulfilled the Rome IV Diagnostic Criteria for functional abdominal pain disorders were enrolled. Melatonin 3 or 5 mg in combination with Lactobacillus Rhamnosus GG (group 1, n = 22) or a placebo in combination with Lactobacillus Rhamnosus GG (control group, n = 20) were taken in the evening for a period of 4 weeks. The study duration was 12 weeks. The primary study endpoint was represented by clinical improvement at week 12 - defined as at least a 50% reduction in mean abdominal pain index (API) from baseline to week 12. RESULTS: The mean API was reduced by more than 50% between T0 and T2 in the group of children treated with melatonin. However, the difference in the distributions of the variations of the scores between the two groups was not significant between T0 and T2 (P = 0.082), while it was significant between T0 and T1 (P = 0.001). Similar results were obtained by analysing the API variables 'weekly frequency of pain' (item 1) and 'perceived intensity of pain' (item 4) individually. CONCLUSIONS: This is the first study to investigate the role of the combination of melatonin and Lactobacillus Rhamnosus GG in the treatment of children with functional abdominal pain disorders. Melatonin combined with Lactobacillus Rhamnosus GG can be considered a therapeutic option for these conditions in children. © 2023 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

The role of early probiotic supplementation in infants for the prevention of respiratory viral illnesses is unclear. We examined the association of Lactobacillus rhamnosus GG (LGG) supplementation during the first 6 months of life with the frequency and severity of viral illnesses during the first 24 months of life. We conducted a secondary analysis of data from the randomized controlled Trial of Infant Probiotic Supplementation (n = 184). Parents reported the number of respiratory viral illnesses, and a composite severity score was created based on symptoms. A negative binomial regression model and a mixed-effects linear regression model assessed for differences in the number of episodes and severity of episodes between treatment groups, respectively. There was no significant difference in the incidence rate of viral illness episodes or symptom severity between treatment groups. Daily supplementation with LGG in early infancy does not decrease the number or severity of viral illnesses during the first 2 years of life.

PURPOSE: We sought to compare the cost-effectiveness of probiotics and usual care with usual care without probiotics in mechanically ventilated, intensive care unit patients alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT). METHODS: We conducted a health economic evaluation alongside the PROSPECT randomized control trial (October 2013-March 2019). We adopted a public healthcare payer's perspective. Forty-four intensive care units in three countries (Canada/USA/Saudi Arabia) with adult critically ill, mechanically ventilated patients (N = 2,650) were included. Interventions were probiotics (Lactobacillus rhamnosus GG) vs placebo administered enterally twice daily. We collected healthcare resource use and estimated unit costs in 2019 United States dollars (USD) over a time horizon from randomization to hospital discharge/death. We calculated incremental cost-effectiveness ratios (ICERs) comparing probiotics vs usual care. The primary outcome was incremental cost per ventilator-associated pneumonia (VAP) event averted; secondary outcomes were costs per Clostridioides difficile-associated diarrhea (CDAD), antibiotic-associated diarrhea (AAD), and mortality averted. Uncertainty was investigated using nonparametric bootstrapping and sensitivity analyses. RESULTS: Mean (standard deviation [SD]) cost per patient was USD 66,914 (91,098) for patients randomized to probiotics, with a median [interquartile range (IQR)] of USD 42,947 [22,239 to 76,205]. By comparison, for those not receiving probiotics, mean (SD) cost per patient was USD 62,701 (78,676) (median [IQR], USD 41,102 [23,170 to 75,140]; incremental cost, USD 4,213; 95% confidence interval [CI], -2,269 to 10,708). Incremental cost-effectiveness ratios for VAP or AAD events averted, probiotics were dominated by usual care (more expensive, with similar effectiveness). The ICERs were USD 1,473,400 per CDAD event averted (95% CI, undefined) and USD 396,764 per death averted (95% CI, undefined). Cost-effectiveness acceptability curves reveal that probiotics were not cost-effective across wide ranges of plausible willingness-to-pay thresholds. Sensitivity analyses did n

Imidazole-chalcone compounds are recognised for their broad-spectrum antimicrobial properties. Probiotic-friendly, selective new-generation antimicrobials prove to be more efficient in combating gastrointestinal system pathogens. The aim of this study is to identify imidazole-chalcone derivatives that probiotics tolerate and evaluate their in vitro synergistic antimicrobial effects on pathogens. In this study, fifteen previously identified imidazole-chalcone derivatives were analyzed for their in vitro antimicrobial properties against gastrointestinal microorganisms. Initially, the antimicrobial activity of pathogens was measured using the agar well diffusion method, while the susceptibility of probiotics was determined by microdilution. The chosen imidazole-chalcone derivatives were assessed for synergistic effects using the checkerboard method. Four imidazole-chalcone derivatives to which probiotic bacteria were tolerant exhibited antibacterial and antifungal activity against the human pathogens tested. To our knowledge, this study is the first to reveal the fractional inhibitory concentration (FIC) of combinations of imidazole-chalcone derivatives. Indeed, the minimum inhibitory concentrations (MIC) for morpholinyl- (ZDO-3f) and 4-ethylpiperazinyl- (ZDO-3 m) imidazole-chalcones were notably low when tested against E. coli and B. subtilis, with values of 31.25 μg/mL and 125 μg/mL, respectively. The combination of morpholinyl- and 4-ethylpiperazinyl derivatives demonstrated an indifferent effect against E. coli, but an additive effect was observed for B. subtilis. Additionally, it was observed that imidazole-chalcone derivatives did not exhibit any inhibitory effects on probiotic organisms like Lactobacillus fermentum (CECT-5716), Lactobacillus rhamnosus (GG), and Lactobacillus casei (RSSK-591). This study demonstrates that imidazole-chalcone derivatives that are well tolerated by probiotics can potentially exert a synergistic effect against gastrointestinal system pathogens. © 2024. The Author(s).

BACKGROUND: Bacterial genomes span a significant portion of diversity, reflecting their adaptation strategies; these strategies include nucleotide usage biases that affect chromosome configuration. Here, we explore an immuno-synergistic oligodeoxynucleotide (iSN-ODN, named iSN34), derived from Lactobacillus rhamnosus GG (LGG) genomic sequences, that exhibits a synergistic effect on immune response to CpG-induced immune activation. METHODS: The sequence of iSN34 was designed based on the genomic sequences of LGG. Pathogen-free mice were purchased from Japan SLC and maintained under temperature- and light-controlled conditions. We tested the effects of iSN34 exposure in vitro and in vivo by assessing effects on mRNA expression, protein levels, and cell type in murine splenocytes. RESULTS: We demonstrate that iSN34 has a significant stimulatory effect when administered in combination with CpG ODN, yielding enhanced interleukin (IL)-6 expression and production. IL-6 is a pleotropic cytokine that has been shown to prevent epithelial apoptosis during prolonged inflammation. CONCLUSIONS: Our results are the first report of a bacterial-DNA-derived ODN that exhibits immune synergistic activity. The potent over-expression of IL-6 in response to treatment with the combination of CpG ODN and iSN34 suggests a new approach to immune therapy. This finding may lead to novel clinical strategies for the prevention or treatment of dysfunctions of the innate and adaptive immune systems.

Vitamin K (VK), an essential nutrient associated with the clotting cascade, has also been demonstrated to have anticancer properties in various cancer cells including colon cancer cells. Also probiotics have gained interest as potential anticancer agents. Among them, Lactobacillus rhamnosus GG (L.GG) has been shown to inhibit cell proliferation and polyamine biosynthesis as well as to induce apoptosis in different human gastrointestinal cancer cells. Nevertheless, the exact mechanisms involved in these actions are not completely elucidated. Therefore, the aims of the present study were to evaluate in three differently graded human colon cancer cells (namely Caco-2, HT-29 and SW480) the effects of increasing VK1 concentrations, administered alone or in combination with viable L.GG, on the cell proliferation evaluated by MTT test, apoptosis investigated by Bax/Bcl-2 ratio and the percentage of the apoptotic cells, and the cell cycle evaluated by MUSE cell analyzer. Both VK1 and L.GG administered alone up to 72 h, caused inhibition of proliferation, induction of apoptosis and the cell cycle arrest in all the tested colon cancer cells. When VK1 and L.GG were co-administered, the addition of increasing VK1 concentrations potentiated the probiotic antiproliferative effect in a dose-dependent manner, being also related to the individual features of each cell line. The effect was more evident in Caco-2 and HT-29 cells compared to the less differentiated SW480. The enhanced antiproliferative efficacy due to co-administration of L.GG and VK1 could represent a suitable option in a functional food strategy for cancer growth inhibition and chemoprevention.

Background: Food allergies are increasingly recognized as a global health concern, influenced by early-life nutrition and the gut microbiome. This systematic review examined randomized controlled trials from 2005 to 2025 assessing the effects of probiotics, prebiotics, and synbiotics in preventing food allergies. Methods: Fourteen studies involving 5685 participants, including pregnant women, infants, and children with or without diagnosed food allergies, were analyzed. While several interventions demonstrated modulation of gut microbiota and immune responses, most trials reported no statistically significant reduction in IgE-mediated food allergy compared with placebo. Results: Some evidence suggested benefits from early exposure to allergenic foods and specific probiotic strains, such as Lactobacillus rhamnosus GG, particularly in cow's milk allergy. However, heterogeneity in study designs, strains, dosages, and diagnostic criteria limited generalizability. Conclusions: Overall, microbiome-targeted nutritional interventions show biological plausibility but inconsistent clinical efficacy. Future large-scale, standardized, and mechanistic studies integrating microbiome, genetic, and environmental data are warranted to define optimal strategies for allergy prevention.

BACKGROUND: Children with attention deficit hyperactivity disorder (ADHD) may benefit from probiotics and prebiotics, but the effects are unclear. To determine whether probiotics and prebiotics affect children with ADHD, a systematic review was conducted. METHODS: The present systematic review analyzed cohort studies and randomized controlled trials that examined whether prebiotics and probiotics are associated with ADHD. Seven randomized controlled trials and two cohort studies met our inclusion criteria. RESULTS: Research on Lactobacillus rhamnosus GG (LGG) probiotic supplementation showed that children with ADHD had better emotional, physical, social, and school functioning, and a higher health-related quality of life compared to the placebo group. The studies also showed that Synbiotic 2000 reduces markers of intestinal and vascular inflammation in children with ADHD, in part through increasing SCFA levels. CONCLUSION: The use of probiotics and prebiotics as adjuvants therapy in patients with ADHD is beneficial. Further studies with longer duration, including more participants and a variety of age groups, and using various evaluation techniques such as in vivo observation are required to examine the effects of prebiotics and probiotics on ADHD. © 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.

Cardiovascular diseases (CVDs) represent the leading cause of death in individuals worldwide. Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) can be metabolized from phosphatidylcholine, choline, and l-carnitine and may play an important role in CVD etiology. Thus, this systematic review aimed to evaluate the effect of probiotics to mitigate TMAO concentrations by gut microbiota modulation. A systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol from databases: PubMed, Web of Sciences, CENTRAL, and Scopus. Controlled intervention studies published until January 3, 2022, with a population at cardiovascular risk were included. The risk of bias was assessed by RoB 2.0 and SYRCLE's for humans and animals' studies, respectively. The search in the database returned 5389 studies, of which 8 matched all criteria to final qualitative analysis. Four studies were controlled trials with humans (total population = 115) and 4 were animal model studies. The body of evidence on the use of probiotics to reduce TMAO concentrations shows that only a few strains have this beneficial effect. This review can conclude that Lactobacillus rhamnosus GG were the most efficient strains in reducing the plasma TMAO level in both humans and animals. In addition, it is worth mentioning the promising character of Lactobacillus plantarum ZDY04, Lactobacillus amylovorus LAM 1345, Lactiplantibacillus plantarum LP1145, and Enterobacter aerogenes ZDY01 for having had the same effect in animals. Published by Elsevier Inc.

OBJECTIVE: To assess the efficacy and safety of different modalities of bladder instillation in patients with neurogenic bladder practicing intermittent catheterization. METHODS: A systematic review of the literature were conducted using two databases: Medline via PubMed and Scopus. Articles evaluating bladder instillation in patients with neurogenic bladder, who are practicing intermittent catheterization, were collected and assessed for the efficacy and safety of the studied agent by two different reviewers. RESULTS: Among the 1896 studies, eight involving 346 patients with neurogenic bladder, were included in this systematic review according to the PRISMA protocols. Gentamicin, Hyaluronic acid, and Lactobacillus rhamnosus was found to decrease the incidence of urinary tract infections, the former reduced multidrug-resistant organisms. Kanamycin-colistin, showed a drop in the mean incidence of bacteriuria in males only. Trisdine, the only studied antiseptic, significantly reduced bacteriuria. Neomycin, however, showed no efficacy in term of bacteriuria. Regarding safety, when evaluated, no major adverse events were reported with any of the studied modalities. CONCLUSION: Bladder instillations of either antibiotics, antiseptics, hyaluronic acid, or Lactobacillus rhamnosus GG are efficient and safe in patients having neurogenic bladder, with recurrent urinary tract infections and practicing clean intermittent catheterization, with gentamicin being the most recommended product among the different studied agents.

BACKGROUND: Antibiotic-associated diarrhoea (AAD) is the most common intestinal side effect of an antibiotic therapy. Various probiotics or probiotic combinations are often used preventively while taking antibiotics for the prevention of AAD. METHOD: This review is based on a systematic literature research in MEDLINE and EMBASE. 7 probiotics are presented with regard to their effectiveness and evidence in the prevention of AAD. Only preparations classified by the World Gastroenerology Organization (WGO) with evidence levels 1-3 for the prevention of AAD were taken into account. 37 clinical studies, including 33 RCTs, were evaluated. RESULTS: Saccharomyces (S.) boulardii CNCM I-745 is the most extensively studied probiotic regarding the prevention of AAD. It has shown evidence-based efficacy in all patient groups (outpatients and hospitalized children and adults). Lactobacillus rhamnosus GG also has a good evidence regarding the prevention of AAD in children and outpatient adults. The other probiotics and probiotic combinations evaluated in the present study only show efficacy in hospitalized patients or only show very limited evidence regarding their efficacy in the prevention of AAD due to the underlying study design or the small number of patients. CONCLUSION: The effect of probiotics is strain-specific, no general statement can be made about the efficacy of probiotics in the prevention of AAD. In principle, it is advisable to select a probiotic with an evidence-based effect such as S. boulardii CNCM I-745 or Lactobacillus rhamnosus GG to prevent AAD. Publisher: Hintergrund: Die Antibiotika-assoziierte Diarrhö (AAD) stellt die häufigste intestinale Nebenwirkung einer Antibiotikatherapie dar. Verschiedene Probiotika oder Probiotikakombinationen werden oft während der Antibiotikaeinnahme präventiv angewendet, um der Entstehung einer AAD vorzubeugen.Methode: Die Übersichtsarbeit basiert auf einer systematischen Literaturrecherche in MEDLINE und EMBASE. Es werden 7 Probiotika hinsichtlich ihrer Wirksamkeit und Evidenz bei der Prävention der AAD dargestellt. Nur Präparate, die von der World Gastroenerology Organisation (WGO) mit Evidenzlevel 1-3 zur Prävention der