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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 -
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 -
Cell Host & Microbe Nov 2018The gut microbiota can be altered by dietary interventions to prevent and treat various diseases. However, the mechanisms by which food products modulate commensals...
The gut microbiota can be altered by dietary interventions to prevent and treat various diseases. However, the mechanisms by which food products modulate commensals remain largely unknown. We demonstrate that plant-derived exosome-like nanoparticles (ELNs) are taken up by the gut microbiota and contain RNAs that alter microbiome composition and host physiology. Ginger ELNs (GELNs) are preferentially taken up by Lactobacillaceae in a GELN lipid-dependent manner and contain microRNAs that target various genes in Lactobacillus rhamnosus (LGG). Among these, GELN mdo-miR7267-3p-mediated targeting of the LGG monooxygenase ycnE yields increased indole-3-carboxaldehyde (I3A). GELN-RNAs or I3A, a ligand for aryl hydrocarbon receptor, are sufficient to induce production of IL-22, which is linked to barrier function improvement. These functions of GELN-RNAs can ameliorate mouse colitis via IL-22-dependent mechanisms. These findings reveal how plant products and their effects on the microbiome may be used to target specific host processes to alleviate disease.
Topics: Animals; Bacterial Proteins; Colitis; Disease Models, Animal; Disease Susceptibility; Exosome Multienzyme Ribonuclease Complex; Female; Food; Gastrointestinal Microbiome; Germ-Free Life; Host-Pathogen Interactions; Immunity, Mucosal; Indoles; Interleukins; Intestines; Lacticaseibacillus rhamnosus; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Plants; RNA, Ribosomal, 16S; Receptors, Aryl Hydrocarbon; Serine Endopeptidases; Tryptophan; Interleukin-22
PubMed: 30449315
DOI: 10.1016/j.chom.2018.10.001 -
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 -
Microbial Cell Factories Aug 2014Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of... (Review)
Review
Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of gastro-intestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms. However, not all intervention studies could show a clinical benefit and even for the same conditions, the results are not univocal. Clearly, the host phenotype governed by age, genetics and environmental factors such as the endogenous microbiota, plays a role in whether individuals are responders or non-responders. However, we believe that a detailed knowledge of the bacterial physiology and the LGG molecules that play a key role in its host-interaction capacity is crucial for a better understanding of its potential health benefits. Molecules that were yet identified as important factors governing host interactions include its adhesive pili or fimbriae, its lipoteichoic acid molecules, its major secreted proteins and its galactose-rich exopolysaccharides, as well as specific DNA motifs. Nevertheless, future studies are needed to correlate specific health effects to these molecular effectors in LGG, and also in other probiotic strains.
Topics: Anti-Infective Agents; Bacterial Adhesion; Fimbriae, Bacterial; Host-Pathogen Interactions; Humans; Intestines; Lacticaseibacillus rhamnosus; Lipopolysaccharides; Polysaccharides, Bacterial; Teichoic Acids
PubMed: 25186587
DOI: 10.1186/1475-2859-13-S1-S7 -
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 -
The ISME Journal Mar 2016Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with... (Clinical Trial)
Clinical Trial
Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut.
Topics: Animals; Bacteria; Butyrates; Caseins; Cattle; Feces; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Infant; Lacticaseibacillus rhamnosus; Male; Milk Hypersensitivity; Probiotics
PubMed: 26394008
DOI: 10.1038/ismej.2015.151 -
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 -
Journal of Translational Medicine Mar 2023Gut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the...
BACKGROUND
Gut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the efficacy of certain anti-cancer treatments. Among the most characterized probiotics, Lactobacillus rhamnosus GG (LGG) is currently utilized in clinics to alleviate diarrhea, mucositis or intestinal damage which might be associated with several triggers, including Clostridium difficile infections, inflammatory gut diseases, antibiotic consumption, chemotherapy or radiation therapy. Here, we investigate whether LGG cell-free supernatant (LGG-SN) might exert anti-proliferative activity toward colon cancer and metastatic melanoma cells. Moreover, we assess the potential adjuvant effect of LGG-SN in combination with anti-cancer drugs.
METHODS
LGG-SN alone or in combination with either 5-Fuorouracil and Irinotecan was used to treat human colon and human melanoma cancer cell lines. Dimethylimidazol-diphenyl tetrazolium bromide assay was employed to detect cellular viability. Trypan blue staining, anti-cleaved caspase-3 and anti-total versus anti-cleaved PARP western blots, and annexin V/propidium iodide flow cytometry analyses were used to assess cell death. Flow cytometry measurement of cellular DNA content (with propidium iodide staining) together with qPCR analysis of cyclins expression were used to assess cell cycle.
RESULTS
We demonstrate that LGG-SN is able to selectively reduce the viability of cancer cells in a concentration-dependent way. While LGG-SN does not exert any anti-proliferative activity on control fibroblasts. In cancer cells, the reduction in viability is not associated with apoptosis induction, but with a mitotic arrest in the G2/M phase of cell cycle. Additionally, LGG-SN sensitizes cancer cells to both 5-Fluorouracil and Irinotecan, thereby showing a positive synergistic action.
CONCLUSION
Overall, our results suggest that LGG-SN may contain one or more bioactive molecules with anti-cancer activity which sensitize cancer cells to chemotherapeutic drugs. Thus, LGG could be proposed as an ideal candidate for ground-breaking integrated approaches to be employed in oncology, to reduce chemotherapy-related side effects and overcome resistance or relapse issues, thus ameliorating the therapeutic response in cancer patients.
Topics: Humans; Lacticaseibacillus rhamnosus; Irinotecan; Propidium; Colon; Adjuvants, Immunologic; Melanoma; Probiotics
PubMed: 36918929
DOI: 10.1186/s12967-023-04036-3 -
EBioMedicine May 2023Probiotics have been increasingly proposed for enhancing immune checkpoint blockade (ICB) treatments against cancer. However, its causal relationship with...
BACKGROUND
Probiotics have been increasingly proposed for enhancing immune checkpoint blockade (ICB) treatments against cancer. However, its causal relationship with immunotherapeutic efficacy remains unclear, which promoted us to explore if and how probiotic Lacticaseibacillus rhamnosus Probio-M9 manipulates gut microbiome for expected outcomes.
METHODS
We evaluated the effects of Probio-M9 on the anti-PD-1 treatment against colorectal cancer in mice via a multi-omics approach. We defined the mechanisms of Probio-M9-mediated antitumor immunity by comprehensive analyses of metagenome and metabolites of commensal gut microbes as well as the immunologic factors and serum metabolome of the host.
FINDINGS
The results indicated that Probio-M9 intervention strengthened the anti-PD-1-based tumor inhibition. Both prophylactic and therapeutic administration of Probio-M9 showed conspicuous performance in controlling tumor growth with ICB treatment. The supplement of Probio-M9 modulated enhanced immunotherapy response through promoting beneficial microbes (e.g., Lactobacillus and Bifidobacterium animalis), producing beneficial metabolites including butyric acids in the gut, and accumulating blood-derived α-ketoglutaric acid, N-acetyl-l-glutamic acid and pyridoxine in particular, which promoted the infiltration and activation of cytotoxic T lymphocytes (CTLs) and suppressing the function of regulatory T cells (Tregs) in the tumor microenvironment (TME). Subsequently, we found that enhanced immunotherapeutic response was transmissible by transplanting either post-probiotic-treatment gut microbes or intestinal metabolites to new tumor-bearing mice.
INTERPRETATION
This study offered valuable insight into the causal role of Probio-M9 in correcting the defects in gut microbiota that compromised anti-PD-1 therapeutic efficacy, which can be used as an alternative synergetic agent with ICB for clinical cancer treatment.
FUNDING
This research was supported by Research Fund for the National Key R&D Program of China (2022YFD2100702), Inner Mongolia Science and Technology Major Projects (2021ZD0014), and China Agriculture Research System of MOF and MARA.
Topics: Animals; Mice; Dietary Supplements; Lacticaseibacillus; Lacticaseibacillus rhamnosus; Neoplasms; Probiotics; Tumor Microenvironment; Immune Checkpoint Inhibitors
PubMed: 37027929
DOI: 10.1016/j.ebiom.2023.104533