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Archivos Argentinos de Pediatria Feb 2022Preterm birth, C-sections, antibiotics, and limited breastfeeding contribute to the increase in noncommunicable diseases. Our objective was to perform a descriptive... (Review)
Review
Preterm birth, C-sections, antibiotics, and limited breastfeeding contribute to the increase in noncommunicable diseases. Our objective was to perform a descriptive review of probiotic use in pediatrics, focused on Lactobacillus rhamnosus GG. Certain probiotics have demonstrated to be effective in acute diarrhea and antibiotic-associated diarrhea. L. rhamnosus GG and Saccharomyces boulardii may shorten their duration and symptoms. L. reuteri DSM 17938 and L. rhamnosus GG were effective to manage infant colic. The use of this strain in infant formulas for cow's milk protein allergy may promote an earlier tolerance acquisition. In relation to the prevention of atopic dermatitis, the administration of L. rhamnosus GG during pregnancy reduced its development in the infant. The use of probiotics as adjuvants is a possibility to consider in current pediatric practice.
Topics: Animals; Cattle; Child; Female; Humans; Infant, Newborn; Lacticaseibacillus rhamnosus; Milk Hypersensitivity; Pediatrics; Premature Birth; Probiotics
PubMed: 35068121
DOI: 10.5546/aap.2022.eng.e1 -
Microorganisms Mar 2023Lactobacilli are widely found in nature, are commensal microbes in humans, and are commonly used as probiotics. Concerns about probiotic safety have arisen due to... (Review)
Review
Lactobacilli are widely found in nature, are commensal microbes in humans, and are commonly used as probiotics. Concerns about probiotic safety have arisen due to reports of bacteremia and other -associated infections. We reviewed the literature for articles on the pathogenicity of spp. bacteremia and reports of probiotics in these patients. Our aim is to review these articles and update the present knowledge on the epidemiology of spp. bacteremia and determine the role of probiotics in bacteremia. bacteremia is infrequent but has a higher risk of mortality and risk factors, including severe underlying diseases, immune system suppression, admission to intensive care units, and use of central venous catheters. A variety of species may cause bacteremia and may or may not be associated with probiotic exposure. To determine if oral probiotics are the source of these infections, the blood isolates and the oral probiotic strain(s) must be compared by sensitive identification methods. The prevalence of bacteremia is infrequent but is more common in patients taking probiotics compared to those not taking probiotics. Three probiotics ( GG, , and ) were directly linked with blood isolates from bacteremia patients using molecular identification assays.
PubMed: 37110319
DOI: 10.3390/microorganisms11040896 -
Gut Microbes 2023With increasing knowledge about the gut - bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being...
BACKGROUND
With increasing knowledge about the gut - bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of GG (LGG) on ovariectomized (OVX) model rats and the immunological and microecological mechanisms involved.
RESULTS
We found a protective effect of LGG treatment in OVX rats through changes in bone microarchitecture, bone biomechanics, and CTX-I, PINP, Ca, and RANKL expression levels. LGG was more advantageous in promoting osteogenesis, which may be responsible for the alleviation of osteoporosis. Th17 cells were imbalanced with Treg cells in mediastinal lymph nodes and bone marrow, with RORγt and FOXP3 expression following a similar trend. TNF-α and IL-17 expression in colon and bone marrow increased, while TGF-β and IL-10 expression decreased; however, LGG treatment modulated these changes and improved the Th17/Treg balance significantly. Regarding the intestinal barrier, we found that LGG treatment ameliorated estrogen deficiency-induced inflammation and mucosal damage and increased the expression of GLP-2 R and tight junction proteins. Importantly, 16S rRNA sequencing showed a significant increase in the Firmicutes/Bacteroidetes ratio during estrogen deficiency. Dominant intestinal flora showed significant differences in composition; LGG treatment regulated the various genera that were imbalanced in OVX, along with modifying those that did not change significantly in other groups with respect to the intestinal barrier, inflammation development, and bile acid metabolism.
CONCLUSIONS
Overall, LGG ameliorated estrogen deficiency-induced osteoporosis by regulating the gut microbiome and intestinal barrier and stimulating Th17/Treg balance in gut and bone.
Topics: Rats; Animals; Gastrointestinal Microbiome; Lacticaseibacillus rhamnosus; T-Lymphocytes, Regulatory; Th17 Cells; RNA, Ribosomal, 16S; Osteoporosis; Estrogens; Inflammation; Probiotics
PubMed: 36941563
DOI: 10.1080/19490976.2023.2190304 -
The American Journal of Gastroenterology Jul 2021It is unclear whether the alleged efficacy of probiotics in childhood acute gastroenteritis depends on the duration and severity of symptoms before treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
It is unclear whether the alleged efficacy of probiotics in childhood acute gastroenteritis depends on the duration and severity of symptoms before treatment.
METHODS
Preplanned secondary analysis of 2 randomized placebo-controlled trials in children 3-48 months of age was conducted in 16 emergency departments in North America evaluating the efficacy of 2 probiotic products (Lactobacillus rhamnosus GG and a combination probiotic: L. rhamnosus and L. helveticus). Participants were categorized in severity groups according to the duration (<24, 24-<72, and ≥72 hours) and the frequency of diarrhea episodes in the 24 hours (≤3, 4-5, and ≥6) before presentation. We used regression models to assess the interaction between pretreatment diarrhea severity groups and treatment arm (probiotic or placebo) in the presence of moderate-to-severe gastroenteritis (Modified Vesikari Scale score ≥9). Secondary outcomes included diarrhea frequency and duration, unscheduled healthcare provider visits, and hospitalization.
RESULTS
A total of 1,770 children were included, and 882 (50%) received a probiotic. The development of moderate-to-severe gastroenteritis symptoms after the initiation of treatment did not differ between groups (probiotic-18.4% [162/882] vs placebo-18.3% [162/888]; risk ratio 1.00; 95% confidence interval 0.87, 1.16; P = 0.95). There was no evidence of interaction between baseline severity and treatment (P = 0.61) for the primary or any of the secondary outcomes: diarrhea duration (P = 0.88), maximum diarrheal episodes in a 24-hour period (P = 0.87), unscheduled healthcare visits (P = 0.21), and hospitalization (P = 0.87).
DISCUSSION
In children 3-48 months with acute gastroenteritis, the lack of effect of probiotics is not explained by the duration of symptoms or frequency of diarrheal episodes before presentation.
Topics: Child, Preschool; Diarrhea; Female; Gastroenteritis; Humans; Infant; Lactobacillus helveticus; Lacticaseibacillus rhamnosus; Male; Probiotics; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 34183579
DOI: 10.14309/ajg.0000000000001295 -
Gut Mar 2022Our goals were to evaluate the antitumour efficacy of GG (LGG) in combination with immune checkpoint blockade (ICB) immunotherapies on tumour growth and to investigate...
OBJECTIVE
Our goals were to evaluate the antitumour efficacy of GG (LGG) in combination with immune checkpoint blockade (ICB) immunotherapies on tumour growth and to investigate the underlying mechanisms.
DESIGN
We used murine models of colorectal cancer and melanoma to evaluate whether oral administration of LGG improves the efficacy of ICB therapies. We performed the whole genome shotgun metagenome sequencing of intestinal contents and RNA sequencing of dendritic cells (DCs). In a series of in vitro and in vivo experiments, we further defined the immunological and molecular mechanisms of LGG-mediated antitumour immunity.
RESULTS
We demonstrate that oral administration of live LGG augmented the antitumour activity of anti-programmed cell death 1 (PD-1) immunotherapy by increasing tumour-infiltrating DCs and T cells. Moreover, the combination treatment shifted the gut microbial community towards enrichment in and , that are known to increase DC activation and CD8tumour recruitment. Mechanistically, treatment with live LGG alone or in combination with anti-PD-1 antibody triggered type I interferon (IFN) production in DCs, enhancing the cross-priming of antitumour CD8 T cells. In DCs, cyclic GMP-AMP synthase (cGAS)/stimulator of IFN genes (STING) was required for IFN-β induction in response to LGG, as evidenced by the significant decrease in IFN-β levels in cGAS or STING-deficient DCs. LGG induces IFN-β production via the cGAS/STING/TANK binding kinase 1/interferon regulatory factor 7 axis in DCs.
CONCLUSION
Our findings have offered valuable insight into the molecular mechanisms of live LGG-mediated antitumour immunity and establish an empirical basis for developing oral administration of live LGG as a combination agent with ICB for cancer therapies.
Topics: Administration, Oral; Animals; Colorectal Neoplasms; Disease Models, Animal; Immune Checkpoint Inhibitors; Interferon Type I; Lacticaseibacillus rhamnosus; Melanoma; Mice; Probiotics
PubMed: 33685966
DOI: 10.1136/gutjnl-2020-323426 -
Nutrients Apr 2021Probiotics seem to have promising effects in the prevention and treatment of allergic conditions including atopic dermatitis (AD) and food allergy. The purpose of this... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effectiveness of Probiotic and Strains in Children with Atopic Dermatitis and Cow's Milk Protein Allergy: A Multicenter, Randomized, Double Blind, Placebo Controlled Study.
Probiotics seem to have promising effects in the prevention and treatment of allergic conditions including atopic dermatitis (AD) and food allergy. The purpose of this multicenter randomized placebo-controlled trial was to evaluate the effectiveness of a probiotic preparation comprising ŁOCK 0900, ŁOCK 0908, and ŁOCK 0918 in children under 2 years of age with AD and a cow's milk protein (CMP) allergy. The study enrolled 151 children, who-apart from being treated with a CMP elimination diet-were randomized to receive the probiotic preparation at a daily dose of 10 bacteria or a placebo for three months, with a subsequent nine-month follow-up. The primary outcomes included changes in AD symptom severity assessed with the scoring AD (SCORAD) index and in the proportion of children with symptom improvement (a SCORAD score decreased by at least 30% in comparison with that at baseline). After the three-month intervention, both the probiotic and placebo groups showed a significant ( < 0.0001) decrease in SCORAD scores, which was maintained nine months later. The percentage of children who showed improvement was significantly higher in the probiotic than in the placebo group (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.13-5.8; = 0.012) after three months. Probiotics induced SCORAD improvement mainly in allergen sensitized patients (OR 6.03; 95% CI 1.85-19.67, = 0.001), but this positive effect was not observed after nine months. The results showed that the mixture of probiotic ŁOCK strains offers benefits for children with AD and CMP allergy. Further research is necessary to assess the effect of probiotic supplementation on the development of immune tolerance (NCT04738565).
Topics: Allergens; Animals; Cattle; Dermatitis, Atopic; Double-Blind Method; Humans; Infant; Lacticaseibacillus casei; Lacticaseibacillus rhamnosus; Milk Hypersensitivity; Probiotics
PubMed: 33916192
DOI: 10.3390/nu13041169 -
Hepatology (Baltimore, Md.) Jun 2020Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis...
BACKGROUND AND AIMS
Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic Lactobacillus rhamnosus GG (LGG) on hepatic BA synthesis, liver injury, and fibrosis in bile duct ligation (BDL) and multidrug resistance protein 2 knockout (Mdr2 ) mice.
APPROACH AND RESULTS
Global and intestine-specific farnesoid X receptor (FXR) inhibitors were used to dissect the role of FXR. LGG treatment significantly attenuated liver inflammation, injury, and fibrosis with a significant reduction of hepatic BAs in BDL mice. Hepatic concentration of taurine-β-muricholic acid (T-βMCA), an FXR antagonist, was markedly increased in BDL mice and reduced in LGG-treated mice, while chenodeoxycholic acid, an FXR agonist, was decreased in BDL mice and normalized in LGG-treated mice. LGG treatment significantly increased the expression of serum and ileum fibroblast growth factor 15 (FGF-15) and subsequently reduced hepatic cholesterol 7α-hydroxylase and BA synthesis in BDL and Mdr2 mice. At the molecular level, these changes were reversed by global and intestine-specific FXR inhibitors in BDL mice. In addition, LGG treatment altered gut microbiota, which was associated with increased BA deconjugation and increased fecal and urine BA excretion in both BDL and Mdr2 mice. In vitro studies showed that LGG suppressed the inhibitory effect of T-βMCA on FXR and FGF-19 expression in Caco-2 cells.
CONCLUSION
LGG supplementation decreases hepatic BA by increasing intestinal FXR-FGF-15 signaling pathway-mediated suppression of BA de novo synthesis and enhances BA excretion, which prevents excessive BA-induced liver injury and fibrosis in mice.
Topics: ATP Binding Cassette Transporter, Subfamily B; Animals; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Fibroblast Growth Factors; Gastrointestinal Microbiome; Humans; Intestines; Lacticaseibacillus rhamnosus; Liver Cirrhosis; Mice; Mice, Knockout; Probiotics; Receptors, Cytoplasmic and Nuclear; Signal Transduction; ATP-Binding Cassette Sub-Family B Member 4
PubMed: 31571251
DOI: 10.1002/hep.30975 -
Nutrients Sep 2021Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease. Probiotics have a potential beneficial effect on the prevention of UC onset and relapse in...
Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease. Probiotics have a potential beneficial effect on the prevention of UC onset and relapse in clinical trials. GG ( GG) have shown clinical benefits on UC patients, however, the precise mechanisms are unknown. The aim of this study is to explore the effect of extracellular vesicles released from GG (LGG-EVs) on dextran sulfate sodium (DSS)-induced colitis and propose the underlying mechanism of LGG-EVs for protecting against colitis. The results showed that LGG-EVs could prevent colonic tissue damage and shortening of the colon ( < 0.01), and ameliorate intestinal inflammation by inhibiting TLR4-NF-κB-NLRP3 axis activation. Consistently, the pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-2) were suppressed effectively upon LGG-EVs treatment ( < 0.05). The 16S rRNA sequencing showed that LGG-EVs administration could reshape the gut microbiota in DSS-induced colitis mice, which further alters the metabolism pathways of gut microbiota. These findings propose a novel perspective of GG in attenuating inflammation mediated by extracellular vesicles and offer consideration for developing oral gavage of LGG-EVs for colitis therapies.
Topics: Animals; Biodiversity; Colitis; Cytokines; Dextran Sulfate; Extracellular Vesicles; Fatty Acids; Gastrointestinal Microbiome; Gene Expression Regulation; Inflammation; Lacticaseibacillus rhamnosus; Male; Mice, Inbred C57BL; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Organ Specificity; Principal Component Analysis; Mice
PubMed: 34684320
DOI: 10.3390/nu13103319 -
JAMA Sep 2021Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported.
OBJECTIVE
To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU).
DESIGN, SETTING, AND PARTICIPANTS
Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020).
INTERVENTIONS
Enteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU.
MAIN OUTCOMES AND MEASURES
The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality.
RESULTS
Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P < .001).
CONCLUSIONS AND RELEVANCE
Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02462590.
Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Diarrhea; Female; Humans; Intensive Care Units; Lacticaseibacillus rhamnosus; Male; Middle Aged; Pneumonia, Ventilator-Associated; Probiotics; Respiration, Artificial; Treatment Failure
PubMed: 34546300
DOI: 10.1001/jama.2021.13355 -
Cell Metabolism May 2020Many studies have suggested a role for gut-resident microbes (the "gut microbiome") in modulating host health; however, the mechanisms by which they impact systemic...
Many studies have suggested a role for gut-resident microbes (the "gut microbiome") in modulating host health; however, the mechanisms by which they impact systemic physiology remain largely unknown. In this study, metabolomic and transcriptional profiling of germ-free and conventionalized mouse liver revealed an upregulation of the Nrf2 antioxidant and xenobiotic response in microbiome-replete animals. Using a Drosophila-based screening assay, we identified members of the genus Lactobacillus capable of stimulating Nrf2. Indeed, the human commensal Lactobacillus rhamnosus GG (LGG) potently activated Nrf2 in the Drosophila liver analog and the murine liver. This activation was sufficient to protect against two models of oxidative liver injury, acetaminophen overdose and acute ethanol toxicity. Characterization of the portal circulation of LGG-treated mice by tandem mass spectrometry identified a small molecule activator of Nrf2, 5-methoxyindoleacetic acid, produced by LGG. Taken together, these data demonstrate a mechanism by which intestinal microbes modulate hepatic susceptibility to oxidative injury.
Topics: Animals; Drosophila; Gastrointestinal Microbiome; Hep G2 Cells; Humans; Lacticaseibacillus rhamnosus; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-E2-Related Factor 2; Oxidation-Reduction; Tumor Cells, Cultured
PubMed: 32213347
DOI: 10.1016/j.cmet.2020.03.006