-
Frontiers in Endocrinology 2022Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the gut play essential roles in host immune regulation. However, few clinical results demonstrated probiotic would actually benefit in attenuating glycated hemoglobin (HbA1c) along with inflammatory cytokine levels of the T1DM patients and analyzed their gut microbiota profile at the same time. In this clinical trial, we evaluated the therapeutic efficacy of probiotics on HbA1c along with inflammatory cytokine levels of T1DM patients to determine an alternative administration mode for T1DM medication. The probiotics changed T1DM gut microbiota profile will be measured by next-generation sequencing (NGS).
RESEARCH DESIGN AND METHODS
A randomized, double-blind, placebo-controlled trial was performed at China Medical University Hospital. T1DM patients between 6 and 18 years of age were enrolled. 27 patients were administered regular insulin therapy plus capsules containing probiotic strains subsp. AP-32, MH-68, and subsp. CP-9 daily for 6 months, and 29 patients were administered insulin therapy without extra probiotic supplement as placebo group. The variations of fasting blood glucose and HbA1c in these patients were analyzed. In addition, serum levels of inflammatory cytokines and anti-inflammatory cytokine were assessed using enzyme-linked immunosorbent assay. Patients' stool microbiota were all subjects to NGS analysis.
RESULTS
NGS data showed elevated populations of and in the gut of patients with T1DM who were taking probiotics. Patients with T1DM who were administered probiotics showed significantly reduced fasting blood glucose levels compared with the before-intervention levels. The HbA1c levels of the patients also improved after administration of probiotics. The concentrations of IL-8, IL-17, MIP-1β, RANTES, and TNF-α were significantly reduced and were associated with an increased TGF-β1 expression after probiotic intervention. The persistence effect of glycemic control and immunomodulation were observed even 3 months after discontinuation of the probiotics.
CONCLUSIONS
Here, we found that conventional insulin therapy plus probiotics supplementation attenuated T1DM symptoms than receiving insulin treatment only. Probiotics supplementation with insulin treatment changed gut microbiota and revealed better outcome in stabilizing glycemic levels and reducing HbA1c levels in patients with T1DM through beneficial regulation of immune cytokines.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT03880760.
Topics: Bifidobacterium animalis; Blood Glucose; Cytokines; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Insulin; Ligilactobacillus salivarius; Probiotics
PubMed: 35299968
DOI: 10.3389/fendo.2022.754401 -
Food Microbiology Dec 2013Lactic acid bacteria (LAB) antimicrobial peptides typically exhibit antibacterial activity against food-borne pathogens, as well as spoilage bacteria. Therefore, they... (Review)
Review
Lactic acid bacteria (LAB) antimicrobial peptides typically exhibit antibacterial activity against food-borne pathogens, as well as spoilage bacteria. Therefore, they have attracted the greatest attention as tools for food biopreservation. In some countries LAB are already extensively used as probiotics in food processing and preservation. LAB derived bacteriocins have been utilized as oral, topical antibiotics or disinfectants. Lactobacillus salivarius is a promising probiotic candidate commonly isolated from human, porcine, and avian gastrointestinal tracts (GIT), many of which are producers of unmodified bacteriocins of sub-classes IIa, IIb and IId. It is a well-characterized bacteriocin producer and probiotic organism. Bacteriocins may facilitate the introduction of a producer into an established niche, directly inhibit the invasion of competing strains or pathogens, or modulate the composition of the microbiota and influence the host immune system. This review gives an up-to-date overview of all L. salivarius strains, isolated from different origins, known as bacteriocin producing and/or potential probiotic.
Topics: Animals; Anti-Bacterial Agents; Bacteriocins; Chickens; Gastrointestinal Tract; Humans; Lactobacillus; Probiotics
PubMed: 24010610
DOI: 10.1016/j.fm.2013.05.010 -
Journal of Applied Microbiology Jul 2017The goals of this review are to summarize the current knowledge on the application of Lactobacillus salivarius as a probiotic in animals and humans, and to address... (Review)
Review
The goals of this review are to summarize the current knowledge on the application of Lactobacillus salivarius as a probiotic in animals and humans, and to address safety concerns with its use on live hosts. Overall, several strains of L. salivarius are well established probiotics with multiple applications in animal health, particularly to reduce colonization by gastrointestinal pathogens, and to a lesser extent, as a production and quality aid. In humans, L. salivarius has been used to prevent and treat a variety of chronic diseases, including asthma, cancer, atopic dermatitis and halitosis, and to a much limited extent, to prevent or treat infections. Based on the results from primary research evidence, it seems that L. salivarius does not pose a health risk to animals or humans in the doses currently used for a variety of applications; however, there is a systematic lack of studies assuring the safety of many of the strains intended for clinical use. This review provides researchers in the field with up-to-date information regarding applications and safety of L. salivarius. Furthermore, it helps researchers identify knowledge gaps and potential opportunities for microbiological and clinical research.
PubMed: 28256040
DOI: 10.1111/jam.13438 -
Future Microbiology May 2010Lactobacillus salivarius has been frequently isolated from the mammalian digestive tract and has been studied as a candidate probiotic. Research to date has described... (Review)
Review
Lactobacillus salivarius has been frequently isolated from the mammalian digestive tract and has been studied as a candidate probiotic. Research to date has described the immunomodulatory properties of the species in cell-lines, mice, rats and humans for the alleviation of intestinal disease and the promotion of host well-being. The ability of L. salivarius to inhibit pathogens and tolerate host antimicrobial defenses demonstrates the adaptation of this species to the gastrointestinal niche. L. salivarius is the best characterized of 25 species in the L. salivarius clade of the genus Lactobacillus. Several other species of this clade are candidate probiotics; however, their probiotic potential has not yet been exploited. This review summarizes the research defining the probiotic nature of L. salivarius, by focusing in particular on L. salivarius UCC118 as a representative strain. The emergent research detailing the probiotic potential of other species in this phylogenetic clade will also be discussed.
Topics: Animals; Cell Line; Humans; Immunologic Factors; Lactobacillus; Mice; Probiotics; Rats
PubMed: 20441548
DOI: 10.2217/fmb.10.35 -
MSystems Dec 2022Currently, the regulation of on intestinal stem cells (ISCs) attracts broad attention, but their active ingredients and the underlying mechanism are worthy of further...
Currently, the regulation of on intestinal stem cells (ISCs) attracts broad attention, but their active ingredients and the underlying mechanism are worthy of further study. Previously, host intestinal commensal bacteria were verified to drive the differentiation of ISCs. In this study, the strong bacteriostatic activity of Lactobacillus salivarius and were illustrated, and the components (supernatant, precipitation) of or were further demonstrated to decrease the differentiation of ISCs . Interestingly, antibiotics feeding decreased ISCs differentiation as well. However, the administration of supernatant following antibiotics feeding was shown to promote ISCs differentiation dramatically when compared with the antibiotics feeding group, indicating that some active ingredients existed in its supernatant to promote ISCs activity. Strikingly, , the treatment of supernatant was further confirmed to promote the intestinal organoids' size, budding, and LGR5 expression. Next, the metabolomics analysis of supernatants suggested that succinate might be a crucial metabolite to promote ISCs activity. Further, the succinate treatment (1000 μM) and (50 mM) was confirmed to enhance the expression of LGR5 and PCNA. (a sodium/dicarboxylate cotransporter) was detected in the intestinal organoids and demonstrated to transport succinate into ISCs, as confirmed by the contact of FITC-succinate with ISCs nucleus. Subsequently, high mitochondrial membrane potential and reactive oxygen species levels appeared in the intestinal organoids upon succinate treatment. Collectively, the promotion of on ISCs activity is associated with succinate-induced mitochondrial energy metabolism. In our previous study, Lactobacillus salivarius and were demonstrated to regulate intestinal stem cell activity in hens, but their active ingredients and the underlying mechanism remain unclear. In this study, supernatant was shown to directly promote intestinal stem cell activity. Furthermore, the succinate (a critical metabolite of ) was screened out to promote intestinal stem cell activity. Moreover, the succinate was confirmed to enter intestinal stem cells and induce high mitochondrial energy metabolism, finally promoting intestinal stem cell activity. These findings will advance uncovering the mechanism by which regulate intestinal stem cell activity in chickens.
Topics: Animals; Female; Ligilactobacillus salivarius; Intestinal Mucosa; Succinic Acid; Chickens; Stem Cells; Anti-Bacterial Agents; Energy Metabolism
PubMed: 36413033
DOI: 10.1128/msystems.00903-22 -
Cells Dec 2022spp., as probiotics, have shown efficacy in alleviating nonalcoholic fatty liver disease (NAFLD). Here, we screened a new probiotic strain, SNK-6 ( SNK-6), which was...
spp., as probiotics, have shown efficacy in alleviating nonalcoholic fatty liver disease (NAFLD). Here, we screened a new probiotic strain, SNK-6 ( SNK-6), which was isolated from the ileum of healthy Xinyang black-feather laying hens in China. We investigated the beneficial activity of SNK-6 in a NAFLD model in laying hens and found that SNK-6 inhibited liver fat deposition and decreased serum triglyceride levels and activity of aspartate transaminase and alanine transaminase. MBOAT2 (membrane-bound O-acyltransferase domain containing 2) was directly targeted by miR-130a-5p, which was downregulated in the liver of NAFLD laying hens but reversed after SNK-6 treatment. Downregulation of MBOAT2, SNK-6 supplementation in vivo, and SNK-6 cell culture treatment in vitro suppressed the mRNA expression of genes involved in the PPAR/SREBP pathway. In addition, 250 metabolites were identified in the supernatants of SNK-6 culture media, and most of them participated in metabolic pathways, including amino acid, carbohydrate, and lipid metabolism. Targeted metabolomic analysis revealed that acetate, butyrate, and propionate were the most abundant short-chain fatty acids, while cholic acid, ursodeoxycholic acid, chenodeoxycholic acid, and tauroursodeoxycholic acid were the four most-enriched bile acids among SNK-6 metabolites. This may have contributed to the reparative effect of SNK-6 in the NAFLD chicken model. Our study suggested that SNK-6 alleviated liver damage partly via the miR-130a-5p/MBOAT2 signaling pathway.
Topics: Animals; Female; Non-alcoholic Fatty Liver Disease; Lipid Metabolism; Ligilactobacillus salivarius; Chickens; MicroRNAs
PubMed: 36552896
DOI: 10.3390/cells11244133 -
Journal of Cellular and Molecular... Mar 2018Streptococcus mutans contributes significantly to dental caries, which arises from homoeostasic imbalance between host and microbiota. We hypothesized that Lactobacillus...
Streptococcus mutans contributes significantly to dental caries, which arises from homoeostasic imbalance between host and microbiota. We hypothesized that Lactobacillus sp. inhibits growth, biofilm formation and gene expression of Streptococcus mutans. Antibacterial (agar diffusion method) and antibiofilm (crystal violet assay) characteristics of probiotic Lactobacillus sp. against Streptococcus mutans (ATCC 25175) were evaluated. We investigated whether Lactobacillus casei (ATCC 393), Lactobacillus reuteri (ATCC 23272), Lactobacillus plantarum (ATCC 14917) or Lactobacillus salivarius (ATCC 11741) inhibit expression of Streptococcus mutans genes involved in biofilm formation, quorum sensing or stress survival using quantitative real-time polymerase chain reaction (qPCR). Growth changes (OD600) in the presence of pH-neutralized, catalase-treated or trypsin-treated Lactobacillus sp. supernatants were assessed to identify roles of organic acids, peroxides and bacteriocin. Susceptibility testing indicated antibacterial (pH-dependent) and antibiofilm activities of Lactobacillus sp. against Streptococcus mutans. Scanning electron microscopy revealed reduction in microcolony formation and exopolysaccharide structural changes. Of the oral normal flora, L. salivarius exhibited the highest antibiofilm and peroxide-dependent antimicrobial activities. All biofilm-forming cells treated with Lactobacillus sp. supernatants showed reduced expression of genes involved in exopolysaccharide production, acid tolerance and quorum sensing. Thus, Lactobacillus sp. can inhibit tooth decay by limiting growth and virulence properties of Streptococcus mutans.
Topics: Antibiosis; Bacteriocins; Biofilms; Catalase; Culture Media; Humans; Hydrogen-Ion Concentration; Interferon-gamma; Interleukin-10; Lacticaseibacillus casei; Lactobacillus plantarum; Limosilactobacillus reuteri; Ligilactobacillus salivarius; Leukocytes, Mononuclear; Microbial Sensitivity Tests; Peroxides; Polysaccharides, Bacterial; Primary Cell Culture; Probiotics; Quorum Sensing; Streptococcus mutans; Trypsin
PubMed: 29316223
DOI: 10.1111/jcmm.13496 -
Applied Microbiology and Biotechnology Dec 2021Previously, we found that Lactobacillus salivarius, Lactobacillus agilis, and Lactobacillus aviarius were associated with excellent egg nutrition in native chicken....
Previously, we found that Lactobacillus salivarius, Lactobacillus agilis, and Lactobacillus aviarius were associated with excellent egg nutrition in native chicken. Next, the optimal Lactobacillus combination is worth studying. Here, a total of 120 HyLine hens (30 hens per group contained 3 replicate cells, 10 hens/cell) in the laying peak period were randomly divided into (1) control, (2) L. salivarius + L. agilis, (3) L. salivarius + L. aviarius, and (4) L. agilis + L. aviarius groups, fed with diet only or with corresponding Lactobacilli (10 colony-forming units/hen/day) for 30 days. As a result, L. salivarius + L. agilis feeding could (1) improve egg-laying rate, egg weight, and albumen's amino acid levels; (2) increase Lactobacillus abundance, decrease Escherichia coli abundance, upregulate the tryptophan metabolism pathway-related molecules, and downregulate the primary bile acid biosynthesis pathway-related molecules in intestinal contents; and (3) upregulate oxidative-phosphorylation pathway-related genes, reactive oxygen species levels, and mRNA abundance of Wnt3a, Dll1, Lgr5, CCDN1, and CDK2 in the crypt. Collectively, L. salivarius + L. agilis feeding in hens could improve intestinal microflora and metabolism profile, promote crypt's local energy metabolism and reactive oxygen species levels, and thus enhance Paneth cells and intestinal stem cells activity.Key points• Lactobacilli co-feeding could improve laying performance and egg nutrition.• Lactobacilli co-feeding could improve intestinal microflora and metabolism profile.• Lactobacilli co-feeding could enhance Paneth cells and intestinal stem cells activity.
Topics: Animals; Chickens; Female; Lactobacillus; Ligilactobacillus salivarius; Stem Cells
PubMed: 34708278
DOI: 10.1007/s00253-021-11606-2 -
Journal of Animal Science and... 2020Enterotoxigenic (ETEC) K88 commonly colonize in the small intestine and keep releasing enterotoxins to impair the intestinal barrier function and trigger inflammatory...
BACKGROUND
Enterotoxigenic (ETEC) K88 commonly colonize in the small intestine and keep releasing enterotoxins to impair the intestinal barrier function and trigger inflammatory reaction. Although () has been reported to enhance intestinal health, it remains to be seen whether there is a functional role of in intestinal inflammatory response in intestinal porcine epithelial cell line (IPEC-J2) when stimulated with ETEC K88. In the present study, IPEC-J2 cells were first treated with followed by the stimulation of ETEC K88 for distinct time period. ETEC K88 adherent status, pattern recognition receptors (PRRs) mRNA, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation, the release of pro-inflammation cytokines and cell integrity were examined.
RESULTS
Aside from an inhibited adhesion of ETEC K88 to IPEC-J2 cells, was capable of remarkably attenuating the expression levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-8, Toll-like receptor (TLR) 4, nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein (NLRP) 3 and NLRP6. This alternation was accompanied by a significantly decreased phosphorylation of p38 MAPK and p65 NF-κB during ETEC K88 infection with pretreatment. Western blot analysis revealed that increased the expression levels of zona occludens 1 (ZO-1) and occludin ( < 0.05) in ETEC K88-infected IPEC-J2 cells. Compared with ETEC K88-infected groups, the addition of as well as extra inhibitors for MAPKs and NF-κB to ETEC K88-infected IPEC-J2 cells had the capability to reduce pro-inflammatory cytokines.
CONCLUSIONS
Collectively, our results suggest that might reduce inflammation-related cytokines through attenuating phosphorylation of p38 MAPK and blocking the NF-κB signaling pathways. Besides, displayed a potency in the enhancement of IPEC-J2 cell integrity.
PubMed: 32774852
DOI: 10.1186/s40104-020-00488-5 -
Microorganisms Jul 2022The production performance and disease resistance of laying hens decrease obviously with age. This study aimed to investigate the effects of supplementary Lactobacillus...
The production performance and disease resistance of laying hens decrease obviously with age. This study aimed to investigate the effects of supplementary Lactobacillus salivarius (L. salivarius) SNK-6 on laying performance, the immune-related gene expression in cecal tonsil, and the cecal microbial composition of laying hens. Here, 384 Xinyang black commercial hens (55 weeks old) were randomly allocated to three groups under the same husbandry and dietary regimes: basal diet (Con), the low L. salivarius SNK-6 group (T1: 1.0 × 106 CFU/g), and the high L. salivarius SNK-6 group (T2: 1.0 × 107 CFU/g). The results showed that the feed intake and broken-egg rate in the T1 group were significantly higher than the Con group (p < 0.05). Meanwhile, expressions of intestinal mucosal immune-related genes were significantly upregulated. The 16S rRNA gene sequencing indicated that supplementary L. salivarius SNK-6 had no significant difference in α -diversity and only displayed a trend difference in the β-diversity of cecal microbiota (p = 0.07). LEfSe and random forest were further used to identify bacteria family Enterobacteriaceae, order RF39, genera Ochrobactrum, and Eubacterium as biomarkers between the Con and T1 groups. Genera Ochrobactrum, which had high relative abundance and nodal degree in the T1 and T2 groups, showed a significant positive correlation with the expression of TLR-6, IL-10, MHC-II, and CD40 in cecal tonsils and might play a critical role in activating the host intestinal mucosal immune responses. Overall, dietary supplementary L. salivarius SNK-6 can display an immunomodulatory function, possibly by regulating cecal microbial composition. However, the changes in immune responses may be at the expenditure of corresponding production performance, which needs to be weighed up in practical application.
PubMed: 35889188
DOI: 10.3390/microorganisms10071469