Consumption of salt leads to ameliorate symptoms of metabolic disorder and change of gut microbiota.

PURPOSE: Metabolic diseases caused by high-carbohydrate and/or high-salt diets are becoming major public health concerns. However, the effects of salt on high-carbohydrate diet-induced obesity are unclear. Accordingly, in this study, we investigated the effects of high-salt intake on high-carbohydrate diet-induced obesity. METHODS: We performed a 12-week study on gut microbiota and metabolic changes in high-rice diet (HRD) or HRD supplemented with high-salt (HRS)-fed C57BL/6 J mice by 16S rRNA analysis, glucose and insulin tolerance testing, gut barrier function, western blot and histological analysis. Moreover, the effects of salt on lipid metabolism were confirmed in vitro using 3T3-L1 cells. RESULTS: High salt intake decreased HRD-induced increases in body and white adipose tissue (WAT) weight. Alternatively, HRS did not reverse the observed increases in glucose intolerance and insulin resistance. Moreover, HRD caused changes in the gut microbiota, thereby impairing gut barrier function and increasing inflammation in the liver. HRS altered HRD-induced microbial composition, however, did not ameliorate gut barrier dysfunction or hepatic inflammation. HRS diets regulated the HRD-induced increase in peroxisome proliferator-activated receptor-γ (PPAR-γ) and lipid metabolism-related protein expression. Moreover, within WAT, HRS was found to reverse the observed decrease in adiponectin and increase in PPAR-γ expression induced by HRD. In vitro, high NaCl concentration also significantly reduced 3T3-L1 cell differentiation and modulated lipid metabolism without causing cytotoxicity. CONCLUSION: These results indicate that high salt intake ameliorates metabolic changes associated with a high-rice diet, including changes in fecal microbiota composition.

Prospective clinical evaluation of Momguard non-invasive prenatal test in 1011 Korean high-risk pregnant women.

Clinical performance of the Momguard non-invasive prenatal test (NIPT) was evaluated in a cohort of Korean pregnant women. The foetal trisomies 21, 18 and 13 (T21, T18 and T13) were screened by low-coverage massive parallel sequencing in the maternal blood. Among the 1011 confirmed samples, 32 cases (3.2%) had positive NIPT results. Of these positive cases, 20 cases of T21, all cases of T18 and two cases of T13 had concordant karyotype findings. Only one case out of the remaining 979 negative NIPT samples showed a false negative result. The overall sensitivity and specificity of Momguard to detect the three chromosomal aneuploidies were 96.8% and 99.8%, respectively. Momguard is a clinically useful tool for the detection of T21, T18 and T13 in singleton pregnancy. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.Impact StatementWhat is already known on this subject? The NIPT approach using massive parallel sequencing (MPS) showed high sensitivity and specificity in various clinical studies. These results are based on analysis systems using their own bioinformatics algorithms.What the results of this study add? When this NIPT technology was introduced in Korea, the first biological specimens collected in Korea were transported overseas for processing in overseas laboratories and analysed by other country's analysis methods. We needed our own NIPT algorithm and developed Momguard NIPT for the first time in Korea. This study attempted to evaluate this Momguard NIPT protocol prospectively in a large number of samples obtained from three Korean hospitals.What the implications are of these findings for clinical practice and/or further research? The overall sensitivity and specificity to identify T13, T18 and T21 were 96.8% and 99.8%, respectively. These accuracy values were comparable to that of other studies. From this study, we found that Momguard is a clinically useful tool for the detection of three chromosomal aneuploidies. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.

Immunomodulatory effects of polysaccharide fraction isolated from Fagopyrum esculentum on innate immune system.

The present study investigates the immunomodulatory activities of buckwheat polysaccharide fraction (BPF) from the seed of Fagopyrum esculentum on RAW 264.7 macrophage cell line and Cyclophosphamide-induced immunosuppressed conditions in mice models. The results of in vitro showed that treatment with 0.5-10 µg/mL of BPF can modulate immune responses. MTT assay and nitric oxide production and immune-related cytokine levels were conducted. Treatment with BPF at a dose of 10 µg/mL of BPF increased immune responses on macrophages. Moreover, natural killer (NK) cell cytotoxicity was conducted. The apoptosis of YAC-1 cells increased as the co-culture ratio between spleen cells and YAC-1 cells increased approximately 4- fold compared to the control group from 12.5:1 to 50.0:1. The in-vivo immunomodulatory effects of BPF were evaluated by cyclophosphamide-induced mice model. The immune response of BPF was determined against cyclophosphamide (100 mg/kg) immunosuppressed mice at doses of 50 mg/kg and 100 mg/kg of BPF as compared to control. The results of this study showed that BPF administration increased spleen and thymus indices as well as the leukocytes count in the blood of immunosuppressed mice. All of results suggested that BPF are potentially acts as immunomodulator for activation of immune responses.

Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer.

PURPOSE: This study was performed to evaluate the frequency of mutations in CHEK2, PALB2, MRE11, and RAD50 among Korean patients at high risk for hereditary breast cancer. METHODS: A total of 235 Korean patients with hereditary breast cancer who tested negative for BRCA1/2 mutation were enrolled to this study. Entire coding regions of CHEK2, PALB2, MRE11, and RAD50 were analyzed using massively parallel sequencing (MPS). Sequence variants detected by MPS were confirmed by Sanger sequencing. RESULTS: Six patients (2.5 %) were found to have pathogenic variants in CHEK2 (n = 1), PALB2 (n = 2), MRE11 (n = 1), and RAD50 (n = 2). Among the pathogenic variants, PALB2 c.2257C>T was previously reported in other studies, while CHEK2 c.1245dupC, PALB2 c.1048C>T, MRE11 c.1773_1774delAA, RAD50 c.1276C>T, and RAD50 c.3811_3813delGAA were newly identified in this study. A total of 15 missense variants were found in the four genes among 26 patients; 7 patients had a variant in CHEK2, 11 in PALB2, 2 in MRE11, and 6 in RAD50. When in silico analyses were performed to the 15 missense variants, six variants (CHEK2 c.686A>G, PALB2 c.1492G>T, PALB2 c.3054G>C, MRE11 c.140C>T, RAD50 c.1456C>T, and RAD50 c.3790C>T) were predicted to be deleterious. CONCLUSIONS: Pathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.

Regulation of MicroRNA-Mediated Developmental Changes by the SWR1 Chromatin Remodeling Complex.

The ATP-dependent SWR1 chromatin remodeling complex (SWR1-C) exchanges the histone H2A-H2B dimer with the H2A.Z-H2B dimer, producing variant nucleosomes. Arabidopsis thaliana SWR1-C contributes to the active transcription of many genes, but also to the repression of genes that respond to environmental and developmental stimuli. Unlike other higher eukaryotic H2A.Z deposition mutants (which are embryonically lethal), Arabidopsis SWR1-C component mutants, including arp6, survive and display a pleiotropic developmental phenotype. However, the molecular mechanisms of early flowering, leaf serration, and the production of extra petals in arp6 have not been completely elucidated. We report here that SWR1-C is required for miRNA-mediated developmental control via transcriptional regulation. In the mutants of the components of SWR1-C such as arp6, sef, and pie1, miR156 and miR164 levels are reduced at the transcriptional level, which results in the accumulation of target mRNAs and associated morphological changes. Sequencing of small RNA libraries confirmed that many miRNAs including miR156 decreased in arp6, though some miRNAs increased. The arp6 mutation suppresses the accumulation of not only unprocessed primary miRNAs, but also miRNA-regulated mRNAs in miRNA processing mutants, hyl1 and serrate, which suggests that arp6 has a transcriptional effect on both miRNAs and their targets. We consistently detected that the arp6 mutant exhibits increased nucleosome occupancy at the tested MIR gene promoters, indicating that SWR1-C contributes to transcriptional activation via nucleosome dynamics. Our findings suggest that SWR1-C contributes to the fine control of plant development by generating a balance between miRNAs and target mRNAs at the transcriptional level.

Deep Sequencing of the Medicago truncatula Root Transcriptome Reveals a Massive and Early Interaction between Nodulation Factor and Ethylene Signals.

The legume-rhizobium symbiosis is initiated through the activation of the Nodulation (Nod) factor-signaling cascade, leading to a rapid reprogramming of host cell developmental pathways. In this work, we combine transcriptome sequencing with molecular genetics and network analysis to quantify and categorize the transcriptional changes occurring in roots of Medicago truncatula from minutes to days after inoculation with Sinorhizobium medicae. To identify the nature of the inductive and regulatory cues, we employed mutants with absent or decreased Nod factor sensitivities (i.e. Nodulation factor perception and Lysine motif domain-containing receptor-like kinase3, respectively) and an ethylene (ET)-insensitive, Nod factor-hypersensitive mutant (sickle). This unique data set encompasses nine time points, allowing observation of the symbiotic regulation of diverse biological processes with high temporal resolution. Among the many outputs of the study is the early Nod factor-induced, ET-regulated expression of ET signaling and biosynthesis genes. Coupled with the observation of massive transcriptional derepression in the ET-insensitive background, these results suggest that Nod factor signaling activates ET production to attenuate its own signal. Promoter:ß-glucuronidase fusions report ET biosynthesis both in root hairs responding to rhizobium as well as in meristematic tissue during nodule organogenesis and growth, indicating that ET signaling functions at multiple developmental stages during symbiosis. In addition, we identified thousands of novel candidate genes undergoing Nod factor-dependent, ET-regulated expression. We leveraged the power of this large data set to model Nod factor- and ET-regulated signaling networks using MERLIN, a regulatory network inference algorithm. These analyses predict key nodes regulating the biological process impacted by Nod factor perception. We have made these results available to the research community through a searchable online resource.

Elucidating the triplicated ancestral genome structure of radish based on chromosome-level comparison with the Brassica genomes.

KEYMESSAGE: This study presents a chromosome-scale draft genome sequence of radish that is assembled into nine chromosomal pseudomolecules. A comprehensive comparative genome analysis with the Brassica genomes provides genomic evidences on the evolution of the mesohexaploid radish genome. Radish (Raphanus sativus L.) is an agronomically important root vegetable crop and its origin and phylogenetic position in the tribe Brassiceae is controversial. Here we present a comprehensive analysis of the radish genome based on the chromosome sequences of R. sativus cv. WK10039. The radish genome was sequenced and assembled into 426.2 Mb spanning >98 % of the gene space, of which 344.0 Mb were integrated into nine chromosome pseudomolecules. Approximately 36 % of the genome was repetitive sequences and 46,514 protein-coding genes were predicted and annotated. Comparative mapping of the tPCK-like ancestral genome revealed that the radish genome has intermediate characteristics between the Brassica A/C and B genomes in the triplicated segments, suggesting an internal origin from the genus Brassica. The evolutionary characteristics shared between radish and other Brassica species provided genomic evidences that the current form of nine chromosomes in radish was rearranged from the chromosomes of hexaploid progenitor. Overall, this study provides a chromosome-scale draft genome sequence of radish as well as novel insight into evolution of the mesohexaploid genomes in the tribe Brassiceae.

Construction of a reference genetic map of Raphanus sativus based on genotyping by whole-genome resequencing.

KEY MESSAGE: This manuscript provides a genetic map of Raphanus sativus that has been used as a reference genetic map for an ongoing genome sequencing project. The map was constructed based on genotyping by whole-genome resequencing of mapping parents and F 2 population. Raphanus sativus is an annual vegetable crop species of the Brassicaceae family and is one of the key plants in the seed industry, especially in East Asia. Assessment of the R. sativus genome provides fundamental resources for crop improvement as well as the study of crop genome structure and evolution. With the goal of anchoring genome sequence assemblies of R. sativus cv. WK10039 whose genome has been sequenced onto the chromosomes, we developed a reference genetic map based on genotyping of two parents (maternal WK10039 and paternal WK10024) and 93 individuals of the F2 mapping population by whole-genome resequencing. To develop high-confidence genetic markers, ~83 Gb of parental lines and ~591 Gb of mapping population data were generated as Illumina 100 bp paired-end reads. High stringent sequence analysis of the reads mapped to the 344 Mb of genome sequence scaffolds identified a total of 16,282 SNPs and 150 PCR-based markers. Using a subset of the markers, a high-density genetic map was constructed from the analysis of 2,637 markers spanning 1,538 cM with 1,000 unique framework loci. The genetic markers integrated 295 Mb of genome sequences to the cytogenetically defined chromosome arms. Comparative analysis of the chromosome-anchored sequences with Arabidopsis thaliana and Brassica rapa revealed that the R. sativus genome has evident triplicated sub-genome blocks and the structure of gene space is highly similar to that of B. rapa. The genetic map developed in this study will serve as fundamental genomic resources for the study of R. sativus.

Boseongazepines A-C, pyrrolobenzodiazepine derivatives from a Streptomyces sp. 11A057.

Three new pyrrolobenzodiazepine derivatives, boseongazepines A-C (1-3), were isolated from a culture broth of Streptomyces sp. 11A057, together with the known compound usabamycin B (4). The structures of 1-4 were determined through the analysis of spectroscopic data including extensive 1D-, 2D-NMR, and MS techniques. Cell growth inhibition effects of these compounds were evaluated against Jurkat, K-562, HL-60, and HepG2 cell lines.

Thyme Extract Alleviates High-Fat Diet-Induced Obesity and Gut Dysfunction.

Prolonged intake of a high-fat diet (HFD) disturbs the composition of gut microbiota, contributing to the development of metabolic diseases, notably obesity and increased intestinal permeability. Thyme (Thymus vulgaris L.), an aromatic plant, is known for its several therapeutic properties. In this study, we explored the potential of thyme extract (TLE) to mitigate HFD-induced metabolic derangements and improve the gut environment. Eight-week-old C57BL/6 mice were administered 50 or 100 mg/kg TLE for eight weeks. Administration of 100 mg/kg TLE resulted in decreased weight gain and body fat percentage, alongside the regulation of serum biomarkers linked to obesity induced by a HFD. Moreover, TLE enhanced intestinal barrier function by increasing the expression of tight junction proteins and ameliorated colon shortening. TLE also altered the levels of various metabolites. Especially, when compared with a HFD, it was confirmed that 2-hydroxypalmitic acid and 3-indoleacrylic acid returned to normal levels after TLE treatment. Additionally, we investigated the correlation between fecal metabolites and metabolic parameters; deoxycholic acid displayed a positive correlation with most parameters, except for colon length. In contrast, hypoxanthine was negatively correlated with most parameters. These results suggest a promising role for thyme in ameliorating obesity and related gut conditions associated with a HFD.

Anti-obesity effects of red pepper (Capsicum annuum L.) leaf extract on 3T3-L1 preadipocytes and high fat diet-fed mice.

Patients with obesity mostly have metabolic syndrome and this can lead to multiple health problems. In the present study, we evaluated the anti-obesity effect of water-soluble red pepper (Capsicum annuum L.) leaf extract (PLE) on 3T3-L1 adipocytes and high-fat diet (HFD)-fed mice. The adipocyte lipid content was determined using Oil Red O staining, which revealed that 100 µg mL-1 PLE markedly reduced fat accumulation without affecting the cell viability. PLE exhibited high prebiotic activity scores by modulating probiotic strains, contributing to host health improvement. In vivo investigation in HFD-fed mice revealed that PLE supplementation significantly decreased the HFD-induced increases in the body weight, amount of white adipose tissue, and serum triglyceride, total cholesterol, leptin, and insulin levels. Consistent with its effects on reduced lipid droplet formation in the liver, PLE supplementation suppressed the expression of lipid synthesis-related proteins including SREBP-1, FAS, and PPAR-γ in the liver and increased that of PGC-1α, CPT1, and adiponectin in epididymal WAT. PLE treatment improved intestinal barrier function and inflammation and reduced harmful intestinal enzyme activities in the feces. Collectively, these results indicate that PLE inhibits fat accumulation in HFD-fed mice via the suppression of adipogenesis and lipogenesis, suggesting its potential in preventing obesity.

Gellan gum prevents non-alcoholic fatty liver disease by modulating the gut microbiota and metabolites.

Gellan gum (GG) is an anionic polysaccharide used as an additive in the food industry. However, the effect of GG on gut microbiota regulation and nonalcoholic fatty liver disease (NAFLD) has not yet been investigated. In vitro fermentation experiments have demonstrated that GG promoted the growth of probiotic strains such as Lactiplantibacillus rhamnosus and Bifidobacterium bifidum, producing metabolites beneficial to gut health. In mice, GG reduced hepatic triglyceride content, serum biomarkers, and body fat mass and weight gain induced by a high fat diet. Additionally, GG regulated the gut microbiota including Desulfovibrionales, Deferribacterales, Bacteroidales, and Lactobacillales at the order level and also promoted short-chain fatty acid production. Moreover, GG improved the expression of proteins related to hepatic inflammation and lipid metabolism. Taken together, GG ameliorated NAFLD, possibly by acting on the gut-liver axis via improving the gut health, indicating its potential as a food supplement and/or prebiotic against NAFLD.

Identification and profiling of novel microRNAs in the Brassica rapa genome based on small RNA deep sequencing.

BACKGROUND: MicroRNAs (miRNAs) are one of the functional non-coding small RNAs involved in the epigenetic control of the plant genome. Although plants contain both evolutionary conserved miRNAs and species-specific miRNAs within their genomes, computational methods often only identify evolutionary conserved miRNAs. The recent sequencing of the Brassica rapa genome enables us to identify miRNAs and their putative target genes. In this study, we sought to provide a more comprehensive prediction of B. rapa miRNAs based on high throughput small RNA deep sequencing. RESULTS: We sequenced small RNAs from five types of tissue: seedlings, roots, petioles, leaves, and flowers. By analyzing 2.75 million unique reads that mapped to the B. rapa genome, we identified 216 novel and 196 conserved miRNAs that were predicted to target approximately 20% of the genome's protein coding genes. Quantitative analysis of miRNAs from the five types of tissue revealed that novel miRNAs were expressed in diverse tissues but their expression levels were lower than those of the conserved miRNAs. Comparative analysis of the miRNAs between the B. rapa and Arabidopsis thaliana genomes demonstrated that redundant copies of conserved miRNAs in the B. rapa genome may have been deleted after whole genome triplication. Novel miRNA members seemed to have spontaneously arisen from the B. rapa and A. thaliana genomes, suggesting the species-specific expansion of miRNAs. We have made this data publicly available in a miRNA database of B. rapa called BraMRs. The database allows the user to retrieve miRNA sequences, their expression profiles, and a description of their target genes from the five tissue types investigated here. CONCLUSIONS: This is the first report to identify novel miRNAs from Brassica crops using genome-wide high throughput techniques. The combination of computational methods and small RNA deep sequencing provides robust predictions of miRNAs in the genome. The finding of numerous novel miRNAs, many with few target genes and low expression levels, suggests the rapid evolution of miRNA genes. The development of a miRNA database, BraMRs, enables us to integrate miRNA identification, target prediction, and functional annotation of target genes. BraMRs will represent a valuable public resource with which to study the epigenetic control of B. rapa and other closely related Brassica species. The database is available at the following link: http://bramrs.rna.kr [1].

Auxin response factor gene family in Brassica rapa: genomic organization, divergence, expression, and evolution.

Completion of the sequencing of the Brassica rapa genome enabled us to undertake a genome-wide identification and functional study of the gene families related to the morphological diversity and agronomic traits of Brassica crops. In this study, we identified the auxin response factor (ARF) gene family, which is one of the key regulators of auxin-mediated plant growth and development in the B. rapa genome. A total of 31 ARF genes were identified in the genome. Phylogenetic and evolutionary analyses suggest that ARF genes fell into four major classes and were amplified in the B. rapa genome as a result of a recent whole genome triplication after speciation from Arabidopsis thaliana. Despite its recent hexaploid ancestry, B. rapa includes a relatively small number of ARF genes compared with the 23 members in A. thaliana, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative genomic and mRNA sequencing analyses demonstrated that 27 of the 31 BrARF genes were transcriptionally active, and their expression was affected by either auxin treatment or floral development stage, although 4 genes were inactive, suggesting that the generation and pseudogenization of ARF members are likely to be an ongoing process. This study will provide a fundamental basis for the modification and evolution of the gene family after a polyploidy event, as well as a functional study of ARF genes in a polyploidy crop species.

Bifidobacterium animalis ssp. lactis MG741 Reduces Body Weight and Ameliorates Nonalcoholic Fatty Liver Disease via Improving the Gut Permeability and Amelioration of Inflammatory Cytokines.

Diet-induced obesity is one of the major causes of the development of metabolic disorders such as insulin resistance and nonalcoholic fatty liver disease (NAFLD). Recently, specific probiotic strains have been found to improve the symptoms of NAFLD. We examined the effects of Bifidobacterium animalis ssp. lactis MG741 (MG741) on NAFLD and weight gain, using a mouse model of high-fat-diet (HFD)-induced obesity. HFD-fed mice were supplemented daily with MG741. After 12 weeks, MG741-administered mice exhibited reduced fat deposition, and serum metabolic alterations, including fasting hyperinsulinemia, were modulated. In addition, MG741 regulated Acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein 1 (SREBP-1), and carbohydrate-responsive element-binding protein (ChREBP) expression and lipid accumulation in the liver, thereby reducing the hepatic steatosis score. To determine whether the effects of MG741 were related to improvements in gut health, MG741 improved the HFD-induced deterioration in gut permeability by reducing toxic substances and inflammatory cytokine expression, and upregulating tight junctions. These results collectively demonstrate that the oral administration of MG741 could prevent NAFLD and obesity, thereby improving metabolic health.

A water soluble extract of radish greens ameliorates high fat diet-induced obesity in mice and inhibits adipogenesis in preadipocytes.

Radish (Raphanus sativus L.) is a rich source of nutrients and its greens have reported functionalities. This study aimed to investigate the effects of a water-soluble extract from radish greens (WERG) on adipogenesis in 3T3-L1 adipocytes and high-fat diet-induced obesity in model mice. We also quantified the phytochemical composition of WERG such as glucoraphenin and ferulic acid. These findings show that treatment with 100 µg mL-1 WERG reduced lipid accumulation in 3T3-L1 adipocytes, whereas in mice, the administration of 100 mg kg-1 WERG reduced weight gain and hepatic lipid accumulation and improved the levels of serum lipid biomarkers. Furthermore, WERG treatment improved intestinal permeability and suppressed the activities of harmful intestinal enzymes in feces, thus improving gut health. It also inhibited metabolic endotoxemia and inflammatory marker levels in serum. Moreover, WERG reduced the expression of lipid-metabolism-related proteins in the liver and white adipose tissue. Collectively, these results indicate that WERG may potentiate the anti-obesity effect by improving gut health and regulating lipid metabolism.

Dietary rhamnogalacturonan-â rich extracts of molokhia ameliorate high fat diet-induced obesity and gut dysbiosis.

Obesity is a global health issue associated with increased prevalence of disease and mortality. Molokhia (Corchorus olitorius L.) leaves, used as vegetables in Asia and Africa, comprise abundant water-soluble mucilage polysaccharides. The present study aimed to evaluate the effects of molokhia leaf polysaccharide fraction (MPF) on high-fat diet (HFD)-induced obesity and gut dysbiosis in mice. A significant decrease was observed in the body weight, adipocyte size, triglyceride serum, and low-density lipoprotein cholesterol levels, as well as in the expression of lipid synthesis-related proteins in mice treated with 4 mg/kg of MPF (MPF4). Moreover, the expression of the tight junction protein increased significantly; however, gut permeability and related inflammatory marker levels decreased in the MPF4 group. Furthermore, MPF ameliorated gut dysbiosis, whereas the MPF4 group presented a decreased Firmicutes to Bacteroidetes ratios and an increased abundance of Akkermansia during exposure to HFD. Our findings reveal that rhamnogalacturonan-Ⅰ rich MPF attenuates obesity in mice subjected to HFD by modulating the gut microbiota.

Morinda citrifolia Extract Prevents Alcoholic Fatty Liver Disease by Improving Gut Health.

Alcoholic liver disease (ALD) is a major chronic liver disease. Chronic alcohol consumption induces dysbiosis, disruption of gut barrier function, oxidative stress, inflammation, and changes in lipid metabolism, thereby leading to ALD. In this study, we investigated whether the commercial Morinda citrifolia extract Nonitri can ameliorate ALD symptoms through the gut-liver axis. We used mice chronically administered EtOH and found a marked increase in serum endotoxin levels and biomarkers of liver pathology. Moreover, the EtOH-treated group showed significantly altered gut microbial composition particularly that of Alistipes, Bacteroides, and Muribaculum and disrupted gut barrier function. However, Nonitri improved serum parameters, restored the microbial proportions, and regulated levels of zonula occludens1, occludin, and claudin1. Furthermore, Nonitri suppressed inflammation by inhibiting endotoxin-triggered toll-like receptor 4-signaling pathway and fat deposition by reducing lipogenesis through activating AMP-activated protein kinase in the liver. Furthermore, Pearson's correlation analysis showed that gut microbiota and ALD-related markers were correlated, and Nonitri regulated these bacteria. Taken together, our results indicate that the hepatoprotective effect of Nonitri reduces endotoxin levels by improving gut health, and inhibits fat deposition by regulating lipid metabolism.

Lactococcus lactis KF140 Reduces Dietary Absorption of Nε - (Carboxymethyl)lysine in Rats and Humans via ß-Galactosidase Activity.

Background and Aims: Excessive intake of advanced glycation end products (AGEs), which are formed in foods cooked at high temperatures for long periods of time, has negative health effects, such as inflammatory responses and oxidative stress. Nε-(Carboxymethyl)lysine (CML) is one of the major dietary AGEs. Given their generally recognized as safe status and probiotic functionalities, lactic acid bacteria may be ideal supplements for blocking intestinal absorption of food toxicants. However, the protective effects of lactic acid bacteria against dietary AGEs have not been fully elucidated. Materials and Methods: We investigated the effect of treatment with Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, on the levels and toxicokinetics of CML. The CML reduction efficacies of the Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, were conducted by in vitro test for reducing CML concentration of the casein-lactose reaction product (CLRP) and in vivo test for reducing serum CML level of LL-KF140 administered rats at 2.0 × 108 CFU/kg for14 days. In addition, 12 volunteers consuming LL-KF140 at 2.0 × 109 CFU/1.5 g for 26 days were determined blood CML concentration and compared with that before intake a Parmesan cheese. Results: Administration of LL-KF140 reduced serum CML levels and hepatic CML absorption in rats that were fed a CML-enriched product. In a human trial, the intake of LL-KF140 prevented increases in the serum levels of CML and alanine aminotransferase after consumption of a CML-rich cheese. LL-KF140 was determined to presence in feces through metagenome analysis. Furthermore, ß-galactosidase, one of the L. lactis-produced enzymes, inhibited the absorption of CML and reduced the levels of this AGE, which suggests an indirect inhibitory effect of LL-KF140. This study is the first to demonstrate that an L. lactis strain and its related enzyme contribute to the reduction of dietary absorption of CML.

Polysaccharide fraction from greens of Raphanus sativus alleviates high fat diet-induced obesity.

Radish (Raphanus sativus) greens are commonly used as a vegetable in Korea; however, their anti-obesity effect has not been reported yet. We prepared the polysaccharide fraction of radish greens (PRG) and assessed its anti-obesity activity in high fat diet (HFD)-induced obese C57BL/6J mice. Supplementation with 4 mg/kg PRG reduced weight gain and body fat percentage, and regulated serum biomarkers against HFD-induced obesity. Moreover, PRG treatment improved gut permeability by increasing tight junction protein expression and colon length shortening. HFD intake increased the proportion of Firmicutes and decreased the proportion of Bacteroidetes and Verrucomicrobia; however, PRG supplementation maintained gut microbial composition to normal diet condition. Moreover, PRG reduced HFD-induced increase of lipid metabolism-related protein expression, along with adipocyte size in white adipose tissue. These results indicated that PRG as a potential prebiotic, has anti-obesity properties by improving gut barrier function, modulating gut microbiota and regulating lipid metabolism.