Lactiplantibacillus plantarum 299v supplementation modulates ß-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats.

The increasing incidence of Type 1 diabetes has coincided with the emergence of the low-fiber, high-gluten Western diet and other environmental factors linked to dysbiosis. Since Lactiplantibacillus plantarum 299 v (Lp299v) supplementation improves gut barrier function and reduces systemic inflammation, we studied its effects in spontaneously diabetic DRlyp/lyp rats provided a normal cereal diet (ND) or a gluten-free hydrolyzed casein diet (HCD). All rats provided ND developed diabetes (62.5±7.7 days); combining ND with Lp299v did not improve survival. Diabetes was delayed by HCD (72.2±9.4 days, p = .01) and further delayed by HCD+Lp299v (84.9±14.3 days, p < .001). HCD+Lp299v pups exhibited increased plasma propionate and butyrate levels, which correlated with enriched fecal Bifidobacteriaceae and Clostridiales taxa. Islet transcriptomic and histologic analyses at 40-days of age revealed that rats fed HCD expressed an autophagy profile, while those provided HCD+Lp299v expressed ER-associated protein degradation (ERAD) and antioxidative defense pathways, including Nrf2. Exposing insulinoma cells to propionate and butyrate promoted the antioxidative defense response but did not recapitulate the HCD+Lp299v islet ERAD transcriptomic profile. Here, both diet and microbiota influenced diabetes susceptibility. Moreover, Lp299v supplement modulated antioxidative defense and ER stress responses in ß-cells, potentially offering a new therapeutic direction to thwart diabetes progression and preserve insulin secretion.

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

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 < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1ß, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (Treg) 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.

A randomized placebo-controlled comparison of 2 prebiotic/probiotic combinations in preterm infants: impact on weight gain, intestinal microbiota, and fecal short-chain fatty acids.

OBJECTIVE: To compare the effect of 2 prebiotic/probiotic products on weight gain, stool microbiota, and stool short-chain fatty acid (SCFA) content of premature infants. PATIENTS AND METHODS: This randomized, blinded, placebo-controlled trial included 90 premature infants treated with either a dietary supplement containing 2 lactobacillus species plus fructooligosaccharides (CUL, Culturelle, ConAgra, Omaha, NE), a supplement containing several species of lactobacilli and bifidobacteria plus fructooligosaccharides (PBP, ProBioPlus DDS, UAS Laboratories, Eden Prairie, MN), or placebo (a dilute preparation of Pregestamil formula) twice daily for 28 days or until discharge if earlier. The primary outcome was weight gain. Secondary outcomes were stool bacterial analysis by culture and 16S rDNA quantitative polymerase chain reaction and stool SCFA content measured by high performance liquid chromatography. RESULTS: Both prebiotic/probiotic combinations contained more bacterial species than noted on the label. No significant effect on infant growth of either prebiotic/probiotic supplement was observed. By cultures, 64% of infants receiving PBP became colonized with bifidobacteria, compared with 18% of infants receiving CUL and 27% of infants receiving placebo (chi-square, P = 0.064). No differences were noted between groups in colonization rates for lactobacilli, Gram-negative enteric bacteria, or staphylococci. By 16S rDNA polymerase chain reaction analysis, the bifidobacteria content in the stools of the infants receiving PBP was higher than in the infants receiving CUL or placebo (Kruskal-Wallis, P = 0.011). No significant differences in stool SCFA content were detected between groups. No adverse reactions were noted. CONCLUSIONS: Infants receiving PBP were more likely to become colonized with bifidobacteria. No significant differences in weight gain or stool SCFA content were detected.