The Kynurenine Pathway Is Upregulated by Methyl-deficient Diet and Changes Are Averted by Probiotics

Scope Probiotics exert immunomodulatory effects and may influence tryptophan metabolism in the host. Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl-deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects. Methods and Results Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured. Results MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p < 0.05). In the MDD rats, the probiotics (vs vehicle) cause lower anthranilic acid and a trend towards lower kynurenic acid and picolinic acid. Compared to probiotics alone, probiotics + choline is associated with a reduced enrichment of the bacterial strains in cecum. The interventions have no effect on inflammatory markers. Conclusions Probiotics counterbalance the effect of MDD diet and downregulate downstream metabolites of the kynurenine pathway.publishedVersio

The Kynurenine Pathway Is Upregulated by Methyl-deficient Diet and Changes Are Averted by Probiotics

Scope Probiotics exert immunomodulatory effects and may influence tryptophan metabolism in the host. Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl‐deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects. Methods and Results Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured. Results MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3‐hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p < 0.05). In the MDD rats, the probiotics (vs vehicle) cause lower anthranilic acid and a trend towards lower kynurenic acid and picolinic acid. Compared to probiotics alone, probiotics + choline is associated with a reduced enrichment of the bacterial strains in cecum. The interventions have no effect on inflammatory markers. Conclusions Probiotics counterbalance the effect of MDD diet and downregulate downstream metabolites of the kynurenine pathway

The Magnitude of Global Marine Species Diversity

Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are ∼226,000 eukaryotic marine species described. More species were described in the past decade (∼20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are ∼170,000 synonyms, that 58,000–72,000 species are collected but not yet described, and that 482,000–741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7–1.0 million marine species. Past rates of description of new species indicate there may be 0.5 ± 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century

The effects of Bifidobacterium animalis ssp. lactis B94 on gastrointestinal wellness in adults with Prader–Willi syndrome: study protocol for a randomized controlled trial

Abstract Background Constipation is a frequent problem in adults with Prader–Willi syndrome. Certain probiotics have been shown to improve transit and gastrointestinal symptoms of adults with functional constipation. The aim of this study is to determine the effect of daily consumption of Bifidobacterium animalis ssp. lactis B94 (B. lactis B94) on stool frequency, stool form, and gastrointestinal symptoms in adults with Prader–Willi syndrome. Methods Adults with Prader–Willi syndrome (18–75 years old, n = 36) will be recruited and enrolled in a 20-week, randomized, double-blind, placebo-controlled, crossover study. Study subjects will be randomized to B. lactis B94 or placebo each for a 4-week period, preceded by a 4-week baseline and followed by 4-week washouts. Subjects will complete daily records of stool frequency and stool form (a proxy of transit time). Dietary intake data also will be collected. Stools, one in each period, will be collected for exploratory microbiota analyses. Discussion To our knowledge, this is the first randomized controlled trial evaluating the effectiveness of B. lactis in adults with Prader–Willi syndrome. The results of this study will provide evidence of efficacy for future clinical trials in patient populations with constipation. Trial registration ClinicalTrials.gov (NCT03277157). Registered on 08 September 2017

Anterior open bite correction by Le Fort 1 osteotomies with or without anterior segmentation: Which is more stable?

A retrospective cohort study was conducted to analyze the relapse rate of anterior open bite (AOB) correction comparing Le Fort I osteotomy with and without anterior segmentation. The risk factors that might contribute to relapse were also assessed. Lateral cephalograms obtained at six different times were analyzed. A total of 81 patients with AOB were recruited. Thirty-five patients underwent Le Fort I osteotomy without anterior segmentation and 46 patients underwent anterior segmentation. Le Fort I osteotomy with anterior segmentation resulted in significantly more AOB relapse when compared to that without anterior segmentation at 7 weeks postoperative (15.2% vs. 0%, P = 0.016). During the early postoperative period, factors that contributed to AOB relapse in Le Fort I osteotomy with anterior segmentation were AOB closure 4 mm and inferior positioning of the anterior segment >2 mm. Over the long term, AOB closure �4 mm and intraoral vertical ramus osteotomy as the only mandibular procedure were factors identified as causing more AOB relapse in those treated by Le Fort I osteotomy with anterior segmentation. In conclusion, Le Fort I osteotomy without anterior segmentation was found to be more stable in the surgical correction of AOB in the early and late postoperative periods

A Lacticaseibacillus rhamnosus secretome induces immunoregulatory transcriptional, functional and immunometabolic signatures in human THP-1 monocytes

Abstract Macrophage responses to activation are fluid and dynamic in their ability to respond appropriately to challenges, a role integral to host defence. While bacteria can influence macrophage differentiation and polarization into pro-inflammatory and alternatively activated phenotypes through direct interactions, many questions surround indirect communication mechanisms mediated through secretomes derived from gut bacteria, such as lactobacilli. We examined effects of secretome-mediated conditioning on THP-1 human monocytes, focusing on the ability of the Lacticaseibacillus rhamnosus R0011 secretome (LrS) to drive macrophage differentiation and polarization and prime immune responses to subsequent challenge with lipopolysaccharide (LPS). Genome-wide transcriptional profiling revealed increased M2-associated gene transcription in response to LrS conditioning in THP-1 cells. Cytokine and chemokine profiling confirmed these results, indicating increased M2-associated chemokine and cytokine production (IL-1Ra, IL-10). These cells had increased cell-surface marker expression of CD11b, CD86, and CX3CR1, coupled with reduced expression of the M1 macrophage-associated marker CD64. Mitochondrial substrate utilization assays indicated diminished reliance on glycolytic substrates, coupled with increased utilization of citric acid cycle intermediates, characteristics of functional M2 activity. LPS challenge of LrS-conditioned THP-1s revealed heightened responsiveness, indicative of innate immune priming. Resting stage THP-1 macrophages co-conditioned with LrS and retinoic acid also displayed an immunoregulatory phenotype with expression of CD83, CD11c and CD103 and production of regulatory cytokines. Secretome-mediated conditioning of macrophages into an immunoregulatory phenotype is an uncharacterized and potentially important route through which lactic acid bacteria and the gut microbiota may train and shape innate immunity at the gut-mucosal interface

Gene interaction network map (String 9.1) examining the functional links between genes in specific immune, cellular and compound signaling pathways taken from the Set Distiller analysis.

<p>Selected pathways included apoptosis, NF-κB, MAPK, Jak-STAT, immune response IFN-alpha/beta, toll-like receptor, IL-17 family, immune response IL-23, RIG-I-like receptor, cytokine-cytokine receptor interaction, NOD-like signaling, nitric oxide, superoxide and histamine.</p

Enrichment analysis using Set Distiller analysis from GeneDecks (version 3) showing descriptors/pathways and the number of genes modulated for virus, nervous and disorder related pathways.

<p>Enrichment analysis of pathways are statistically significant with a p-value <0.05 (Bonferroni corrected).</p