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Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation.

ABSTRACT: Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor's PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n?=?4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n?=?15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01?±?0.74 vs. 0.22?±?0.51; P?reg) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.

SUBMITTER: Hofeld BC

PROVIDER: S-EPMC7889883 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation.

Hofeld Benjamin C BC Puppala Venkata K VK Tyagi Sudhi S Ahn Kwang Woo KW Anger Amberly A Jia Shuang S Salzman Nita H NH Hessner Martin J MJ Widlansky Michael E ME

Scientific reports 20210217 1

Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy dono ...[more]

PMID: 33597583

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Project description:RationaleA strong association has emerged between the gut microbiome and atherosclerotic disease. Our recent data suggest Lactobacillus plantarum 299v (Lp299v) supplementation reduces infarct size in male rats. Limited human data are available on the impact of Lp299v on the vasculature.ObjectiveTo determine whether oral Lp299v supplementation improves vascular endothelial function and reduces systemic inflammation in humans with stable coronary artery disease (CAD).Methods and resultsTwenty men with stable CAD consumed a drink containing Lp299v (20 billion CFU) once daily for 6 weeks. After a 4-week washout, subjects were given an option of additionally participating in a 10-day study of oral liquid vancomycin (250 mg QID). Vascular endothelial function was measured by brachial artery flow-mediated dilation. Before and after Lp299v, plasma short-chain fatty acids, trimethylamine oxide, and adipokine levels were measured. Additional plasma samples underwent unbiased metabolomic analyses using liquid chromatography/mass spectroscopy. 16S rRNA sequencing was used to determine changes of the stool microbiome. Arterioles from patients with CAD were obtained, and endothelium-dependent vasodilation was measured by video microscopy after intraluminal incubation with plasma from Lp299v study subjects. Lp299v supplementation improved brachial flow-mediated dilation ( P=0.008) without significant changes in plasma cholesterol profiles, fasting glucose, or body mass index. Vancomycin did not impact flow-mediated dilation. Lp299v supplementation decreased circulating levels of IL (interleukin)-8 ( P=0.01), IL-12 ( P=0.02), and leptin ( P=0.0007) but did not significantly change plasma trimethylamine oxide concentrations ( P=0.27). Plasma propionate ( P=0.004) increased, whereas acetate levels decreased ( P=0.03). Post-Lp299v plasma improved endothelium-dependent vasodilation in resistance arteries from patients with CAD ( P=0.02).16S rRNA analysis showed the Lactobacillus genus was enriched in postprobiotic stool samples without other changes.ConclusionsLp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and trimethylamine oxide. Circulating gut-derived metabolites likely account for these improvements and merit further study.Clinical trial registrationURL: http://www.clinicaltrials.gov . Unique identifier: NCT01952834.

Project description:Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of the pancreatic β-cells. T1D pathogenesis has a strong genetic basis. However, in recent decades, the prevalence of high-risk HLA haplotypes among new diagnoses has declined, the age of onset has decreased, and T1D incidence has increased. These changes are consistent with increased environmental pressure and coincide with introduction of the Western diet, widespread antibiotic use and reduced breast feeding. These factors are thought to drive intestinal dysbiosis, increased gut permeability and systemic inflammation. Notably, our studies of T1D families and the BioBreeding (BB) rat have identified a peripheral inflammatory state associated with diabetes susceptibility that is consistent with microbial antigen exposure and pattern recognition receptor ligation. Lactiplantibacillus plantarum 299v (Lp299v), a probiotic strain, is reported to increase plasma and stool levels of anti-inflammatory short chain fatty acids (SCFA) and promote IL-10 signaling in colonic derived macrophages and T-cells. Here we investigated the effect of Lp299v supplement on T1D progression and inflammatory phenotypes in diabetes prone BB DRlyp/lyp rats. Rats were weaned at 21 days onto a normal cereal diet (ND) or a gluten-free hydrolyzed casein diet (HCD), with and without daily Lp299v supplementation. All DRlyp/lyp ND rats developed T1D by day 83 (mean time to onset of 62.8+/-7.9 days). DRlyp/lyp ND+Lp299v rats exhibited an insignificant delay in T1D onset (62.6+/-6.5 days), however 8% remained diabetes-free to day 130. Providing DRlyp/lyp rats HCD prevented T1D in 17% of rats (to age 130 days) and significantly delayed onset (mean time to onset 72.8+/-7.3 days, p<0.001). Providing DRlyp/lyp rats HCD+Lp299v prevented T1D in 25% of rats and more robustly delayed onset (mean time to onset 84.9 +/-14.3 days, p<0.001). While multiplex ELISA failed to detect significantly altered plasma cytokine/chemokine levels at 40 days of life, plasma induced transcription revealed greatest normalization of systemic inflammation in the HCD+Lp299v group. Plasma SCFA levels (propionate and butyrate, p<0.01) were elevated in the HCD+Lp299v group compared to the ND group. Global gene expression analysis of pancreatic islets was conducted at 40 days, prior to insulitis. Endoplasmic reticulum (ER) stress has been implicated in the formation of islet neoantigens that may underlie the initial loss of immune tolerance in T1D. Under one or both diets, Lp299v favorably modulated islet expression levels of pathways and transcripts related to inflammation and innate immunity (Cxcl9, Cxcl10), oxidative stress (Gsta1, Gsta4, Gstp1, Gstk1), as well as ER stress and unfolded protein response (Cirbp, Edem1, Hspa1a, Atf4). These ongoing studies add to a growing understanding that inherited susceptibility can be modulated by diet and microbiota.

Project description:BACKGROUND:Probiotic microorganisms favorably alter the intestinal microflora balance, promote intestinal integrity and mobility, inhibit the growth of harmful bacteria and increase resistance to infection. Probiotics are increasingly used in nutraceuticals, functional foods or in microbial interference treatment. However, the effectiveness of probiotic organism is considered to be population-specific due to variation in gut microflora, food habits and specific host-microbial interactions. Most of the probiotic strains available in the market are of western or European origin, and a strong need for exploring new indigenous probiotic organisms is felt. METHODS AND FINDINGS:An indigenous isolate Lp9 identified as Lactobacillus plantarum by molecular-typing methods was studied extensively for its functional and probiotic attributes, viz., acid and bile salt tolerance, cell surface hydrophobicity, autoaggregation and Caco-2 cell-binding as well as antibacterial and antioxidative activities. Lp9 isolate could survive 2 h incubation at pH 1.5-2.0 and toxicity of 1.5-2.0% oxgall bile. Lp9 could deconjugate major bile salts like glycocholate and deoxytaurocholate, indicating its potential to cause hypocholesterolemia. The isolate exhibited cell-surface hydrophobicity of approximately 37% and autoaggregation of approximately 31%. Presence of putative probiotic marker genes like mucus-binding protein (mub), fibronectin-binding protein (fbp) and bile salt hydrolase (bsh) were confirmed by PCR. Presence of these genes suggested the possibility of specific interaction and colonization potential of Lp9 isolate in the gut, which was also suggested by a good adhesion ratio of 7.4+/-1.3% with Caco-2 cell line. The isolate demonstrated higher free radical scavenging activity than standard probiotics L. johnsonii LA1 and L. acidophilus LA7. Lp9 also exhibited antibacterial activity against E. coli, L. monocytogenes, S. typhi, S. aureus and B. cereus. CONCLUSION:The indigenous Lactobacillus plantarum Lp9 exhibited high resistance against low pH and bile and possessed antibacterial, antioxidative and cholesterol lowering properties with a potential for exploitation in the development of indigenous functional food or nutraceuticals.

Dataset Information

Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation.

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Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation.

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