Silk-derived sericin/fibroin mixture drink fermented with plant-derived Lactococcus lactis BM32-1 improves constipation and related microbiota: a randomized, double-blind, and placebo-controlled clinical trial.

We previously showed through clinical trials that one plant-derived lactic acid bacteria (LAB) can improve constipation. We preliminarily found that the plant-derived LAB Lactococcus lactis BM32-1 can grow in a mixture of sericin and fibroin, which are extracted from silk and have been reported to help promote health. Thus, in the present study, we evaluated the favorable effect of a sericin/fibroin mixture (S/F-M), which was extracted from silk prepared from cocoons reared in an aseptic rearing system using an artificial diet, fermented with the BM32-1 strain through a clinical trial. The trial was conducted at Hiroshima University from June to October 2022 as a double-blind, placebo-controlled, randomized parallel-group comparative study with 50 eligible subjects (aged 23-71) who had an average defecation frequency of less than 5 times per week. The subjects were instructed to drink 100 mL of fermented S/F-M or placebo every day. After the 12 weeks of the clinical trial period, the average defecation frequency increased significantly-1.4 times higher than that at baseline in the test group-as compared with the placebo group. Furthermore, the fecal microbiota was also compared before and after treatment, revealing that intake of the fermented S/F-M significantly multiplied the relative abundance of the genera Enterococcus and Clostridium, which have been reported to contribute to the amelioration of constipation by improving the gut microbiota and producing butyric acid, respectively. In conclusion, the S/F-M fermented using the BM32-1 strain improves defecation frequency through alteration of the gut microbiota.

Transcriptional profiling of geniposide bioconversion into genipin during gardenia fructus extract fermentation by Lactobacillus (Lactiplantibacillus) plantarum SN13T.

Lactiplantibacillus plantarum SN13T is a probiotic plant-derived lactic acid bacterium that can grow in various medicinal plant extracts. In this study, we fermented an aqueous extract of gardenia fructus, the fruit of a medicinal plant, with SN13T, such that the bioactivity of the extract was potentiated after fermentation to suppress the release of inflammatory mediators, such as nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), as well as downregulate inflammatory genes in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. This increased antioxidant and anti-inflammatory activity was mediated through bioconversion of the iridoid glycoside geniposide to its aglycone genipin via the supposed hydrolytic action of ß-glucosidases harbored by SN13T. In the complete genome of SN13T, ten putative genes encoding ß-glucosidases of glycosyl hydrolase (GH) family 1 organized among eight gene operons were identified. Transcriptional profiling revealed that two 6-phospho-ß-glucosidase genes, pbg9 and SN13T_1925, located adjacently in the gene operon SN13T_1923, were transcribed significantly more than the remaining genes during fermentation of the gardenia extract. This suggests the role of these ß-glucosidases in bioconversion of geniposide to genipin and the subsequent enhanced bioactivity of the gardenia fructus extract after fermentation with SN13T.

Non-pathogenic Heyndrickxia coagulans (Bacillus coagulans) 29-2E inhibits the virulence of pathogenic Salmonella Typhimurium by quorum-sensing regulation.

Bacteria produce and release small signal molecules, autoinducers, as an indicator of their cell density. The system, called a quorum-sensing (QS) system, is used to control not only virulence factors but also antibiotic production, sporulation, competence, and biofilm formation in bacteria. Different from antibiotics, QS inhibitors are expected to specifically repress the virulence factors in pathogenic bacteria without inhibiting growth or bactericidal effects. Therefore, since QS inhibitors have little risk of antibiotic-resistant bacteria emergence, they have been proposed as promising anti-bacterial agents. In the present study, we aimed to find new QS inhibitors that prohibit the signaling cascade of autoinducer 3 (AI-3) recognized by a QseCB two-component system that regulates some virulence factors of pathogens, such as enterohemorrhagic Escherichia coli (EHEC) and Salmonella enterica subsp. enterica serovar Typhimurium. We have established the method for QS-inhibitor screening using a newly constructed plasmid pLES-AQSA. E. coli DH5α transformed with the pLES-AQSA can produce ß-galactosidase that converts 5-bromo-4-chloro-3-indolyl ß-d-galactopyranoside (X-gal) into blue pigment (5-bromo-4-chloro-indoxyl) under the control of the QseCB system. By screening, Heyndrickxia coagulans (formerly Bacillus coagulans) 29-2E was found to produce an exopolysaccharide (EPS)-like water-soluble polymer that prohibits QseCB-mediated ß-galactosidase production without antibacterial activities. Further, the simultaneous injection of the 29-2E strain significantly improves the survival rate of Salmonella Typhimurium-infected silkworm larvae (from 0% to 83.3%), suggesting that the substance may be a promising inhibitor against the virulence of pathogens without risk of the emergence of antibiotic-resistant bacteria.

Resting phase-administration of lemborexant ameliorates sleep and glucose tolerance in type 2 diabetic mice.

Sleep disorders are associated with increased risk of obesity and type 2 diabetes. Lemborexant, a dual orexin receptor antagonist (DORA), is clinically used to treat insomnia. However, the influence of lemborexant on sleep and glucose metabolism in type 2 diabetic state has remained unknown. In the present study, we investigated the effect of lemborexant in type 2 diabetic db/db mice exhibiting both sleep disruption and glucose intolerance. Single administration of lemborexant at the beginning of the light phase (i.e., resting phase) acutely increased total time spent in non-rapid eye movement (NREM) and REM sleep in db/db mice. Durations of NREM sleep-, REM sleep-, and wake-episodes were also increased by this administration. Daily resting-phase administration of lemborexant for 3-6 weeks improved glucose tolerance without changing body weight and glucose-stimulated insulin secretion in db/db mice. Similar improvement of glucose tolerance was caused by daily resting-phase administration of lemborexant in obese C57BL/6J mice fed high fat diet, whereas no such effect was observed in non-diabetic db/m+ mice. Diabetic db/db mice treated daily with lemborexant exhibited increased locomotor activity in the dark phase (i.e., awake phase), although they did not show any behavioral abnormality in the Y-maze, elevated plus maze, and forced swim tests. These results suggest that timely promotion of sleep by lemborexant improved the quality of wakefulness in association with increased physical activity during the awake phase, and these changes may underlie the amelioration of glucose metabolism under type 2 diabetic conditions.

Dendrobium officinale Extract Fermented with Lactobacillus plantarum GT-17F Enhances the Protection of UV-Mediated Photoaging.

Long-term and extensive exposure to UV irradiation can cause sunburn, photoaging, or skin cancer. Various studies have shown that Dendrobium officinale extract has a certain protective effect on skin-related diseases. Lactobacillus plantarum is a probiotic that has been reported to be used for co-fermentation with various plants to enhance the activity of extracts. This article discusses the effectiveness of fermentation of Dendrobium officinale extract with Lactobacillus plantarum GT-17F on protection against UV-mediated photoaging. The study found that fermented extract of Dendrobium officinale (FDO) has a stronger antioxidant effect, especially in free radical scavenging. Pretreatment with FDO enables human skin fibroblast (HSF) cells and reconstruction skin models (EpiSkin and T-Skin) to resist UV-mediated degradation of type I collagen and type III collagen, repair epidermal barrier function, and reduce the damage of barrier-related proteins, such as filaggrin (FLG) and loricrin (LOR). Those findings provide a basis for further studies to evaluate the effectiveness of fermented Dendrobium officinale in preventing UV-mediated damage and photoaging in humans.

Fermented Stevia Improves Alcohol Poisoning Symptoms Associated with Changes in Mouse Gut Microbiota.

We previously found that the continuous feeding of ethanol caused mice dysbiosis, in which the cecal microbiota were significantly altered, as compared with those in the non-feeding control group, especially in some bacterial genera involved in gut inflammation. In the present study, we have found that the fermented extract of stevia (Stevia rebaudiana) leaves with plant-derived lactic acid bacteria (LABs), Pediococcus pentosaceus LY45, improves the trimethylamine (TMA) productivity of cecal content, which can be used as an indicator of dysbiosis. The following animal experiment also shows that the LY45-fermented stevia extract represses the typical increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which decreased from 1106 to 210 IU/L (p < 0.05) and from 591 to 100 IU/L (p < 0.05), respectively, together with the simultaneously latent TMA productivity (from 1356 to 745 µM, p < 0.05) of cecal content in the ethanol-fed mice. The microbiota analyses have shown that the observed increased alterations in pro-inflammatory genera putative SMB53 (family Clostridiaceae) and Dorea are restored by the fermented stevia extract. Our result indicates that the preliminary bioconversion of herbal medicinal precursors by fermentation with safe microorganisms like LABs is expected to be a hopeful method of producing specific metabolites that may contribute to the reconstruction of gut microbiota.

Role of Phenolic Acid Metabolism in Enhancing Bioactivity of Mentha Extract Fermented with Plant-Derived Lactobacillus plantarum SN13T.

Plant-derived lactic acid bacteria are major fermentation organisms that can grow in medicinal herb extracts enriched with phytochemicals like glycosides, phenolic acids, flavonoids, and tannins. Fermentation with strain-specific Lactobacilli harboring metabolic enzymes can increase the bioactivity and bioavailability of medicinal herbs. Fermentation of extracts of Artemisia princeps and Paeonia lactiflora has been previously found to increase their bioactivities. Therefore, this study explores the possibility of increasing the bioactivity of Mentha arvensis (Mentha) extract against lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells by fermenting with plant-derived probiotic strains Lactobacillus (Lact.) plantarum SN13T and Pediococcus (Ped.) pentosaceus LP28. As a result, fermentation with SN13T significantly increased the bioactivity of Mentha extract as compared to unfermented or LP28-fermented extracts. This higher bioactivity was associated with the metabolism of rosmarinic acid (RA) and caffeic acid (CA), the major bioactive phenolic acids reported in Mentha, along with the production of the metabolite dihydrocaffeic acid (DHCA). DHCA was found to be a more potent LPS-induced nitric oxide (NO) inhibitor than its precursor phenolic acids. The metabolism of RA to DHCA via CA could be mediated by the enzymes cinnamoyl ester hydrolase and hydroxycinnamate reductases, encoded by the ceh gene and the hcrRABC gene operon, respectively, which were identified in the complete genome sequence of Lact. plantarum SN13T but were absent in Ped. pentosaceus LP28. The genes hcrA, hcrB, and hcrC were significantly and time-dependently overexpressed in Lact. plantarum SN13T when grown in the Mentha extract, suggesting the role of phenolic acid metabolism in enhancing its bioactivity.

Construction of a Temperature-Sensitive Shuttle Vector between Lactic Acid Bacteria and Escherichia coli and Its Application to a Tn10-Based Random Mutagenesis Tool in Lactic Acid Bacteria.

In the present study, we have obtained a temperature-sensitive replication mutant in the Escherichia (E.) coli-lactic acid bacterium (LAB) shuttle vector pLES003-b carrying erythromycin-resistance gene by error-prone PCR technique. Among 858 clones obtained in the construction of the random mutation libraries of pLES003-b in the ori and repA regions, three clones could grow normally at 28 °C but not at 42 °C. One of the clones was designated as pLES003-b TS1. The sequencing analysis of pLES003-b TS1 revealed that the plasmid has four substitution mutations (376G > A, 435A > T, 914C > A, and 1996T > A) and one insertional mutation (1806_1807insA). Among those mutations, substitution mutation 914C > A, which leads to a CGC-to-AGC codon change at position 44 of the RepA protein (arginine-to-serine substitution mutation: R44S in RepA), was predicted to be a cause of temperature sensitivity. Therefore, the C-to-A substitution was introduced into the repA gene in pLES003-b using a site-directed mutagenesis method, and the resultant plasmid was electroporated into a Lactobacillus (L.) plantarum cell. The resultant transformant cannot grow at 42 °C in the presence of erythromycin, which is used as a selective marker, indicating that the R44S point mutation in the RepA protein may be crucial for temperature sensitivity. Furthermore, we have developed a new plasmid as an efficient genetic engineering tool for random insertional mutagenesis in LABs using a combination of transposon Tn10 and the temperature-sensitive replication system in pLES003-b. The resultant plasmid vector, which was designated pLES-Tn10-TS1, would be useful for genetic analysis of the functional molecule in lactic acid bacterial strains.

A Prospective Study of Neoadjuvant Gemcitabine Plus Nab-paclitaxel in Patients with Borderline-resectable Pancreatic Cancer.

Objectives Neoadjuvant therapy followed by radical resection improves the borderline-resectable pancreatic cancer (BRPC) prognosis; however, the optimal therapeutic regimen remains unclear. Gemcitabine plus nab-paclitaxel (GnP) showed a high anti-tumor effect in primary lesions in a prospective study for metastatic disease. However, evidence concerning its feasibility is still lacking in patients with BRPC. We therefore evaluated the tolerability of neoadjuvant GnP (NAC-GnP) for BRPC. Methods This single-center prospective study evaluated 10 patients with BRPC who were treated with two cycles of NAC-GnP. The primary endpoint was feasibility for NAC-GnP. Treatment feasibility was defined as a successful outcome in at least eight patients. Results Ten patients who had BRPC in contact with the celiac artery (n=5), superior mesenteric artery (n=3), or hepatic artery (n=2) were enrolled. The median age was 75 (range, 40-82) years old. Grade 3 anorexia and grade 2 pneumonia occurred in one patient each, so treatment was feasible in eight patients. The median primary tumor reduction and response rates were 33% (range, 0-68%) and 60%, respectively. Six of eight patients who had abnormal CA19-9 levels at the time of enrolment showed a decrease in CA19-9 levels, with a median decrease of 72%. Five patients underwent radical resection, including R0 resection in four. Postoperative grade IIIa Clavien-Dindo complications occurred in one patient (upper gastrointestinal bleeding and pancreatic fistula). Conclusion Two-cycle NAC-GnP is a feasible treatment for patients with BRPC. Further studies on NAC-GnP in patients with BRPC are warranted.

Food odor perception promotes systemic lipid utilization.

Food cues during fasting elicit Pavlovian conditioning to adapt for anticipated food intake. However, whether the olfactory system is involved in metabolic adaptations remains elusive. Here we show that food-odor perception promotes lipid metabolism in male mice. During fasting, food-odor stimulation is sufficient to increase serum free fatty acids via adipose tissue lipolysis in an olfactory-memory-dependent manner, which is mediated by the central melanocortin and sympathetic nervous systems. Additionally, stimulation with a food odor prior to refeeding leads to enhanced whole-body lipid utilization, which is associated with increased sensitivity of the central agouti-related peptide system, reduced sympathetic activity and peripheral tissue-specific metabolic alterations, such as an increase in gastrointestinal lipid absorption and hepatic cholesterol turnover. Finally, we show that intermittent fasting coupled with food-odor stimulation improves glycemic control and prevents insulin resistance in diet-induced obese mice. Thus, olfactory regulation is required for maintaining metabolic homeostasis in environments with either an energy deficit or energy surplus, which could be considered as part of dietary interventions against metabolic disorders.

Plant-Derived Lactobacillus paracasei IJH-SONE68 Improves the Gut Microbiota Associated with Hepatic Disorders: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

Our previous clinical study has shown that the exopolysaccharide (EPS) produced by a plant-derived lactic acid bacterium, Lactobacillus paracasei IJH-SONE68, improves chronic allergy status in humans. In addition, an inhibition of visceral fat accumulation was observed following the intake of EPS during animal experimentation. In the present study, we have further evaluated the health-promoting effects of a spray-dried powder of pineapple juice that is fermented with the IJH-SONE68 strain. This was conducted in a double-blind, randomized, placebo-controlled, parallel-group clinical trial at Hiroshima University from May 2019 to July 2021. Eighty healthy volunteers at range of ages 23-70, with a body mass index between 25 and 29.99, were enrolled. After the 12 weeks of the experimental period were complete, although the average visceral fat area in both groups similarly decreased, there was no significant difference in the content of visceral fat area or in the obesity-related physical parameters in both groups. Further, we found that the serum liver function indices (AST and ALT) in the test group decreased within a statistically determined trend (p = 0.054). The fecal microflora analysis revealed, in the test group, a statistically significant increase in the relative abundance changes within Anaerostipes, which has been reported to help suppress hepatic inflammation.

3-Phenyllactic acid generated in medicinal plant extracts fermented with plant-derived lactic acid bacteria inhibits the biofilm synthesis of Aggregatibacter actinomycetemcomitans.

In the present study, the effect of PLA on a periodontic pathogen, Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), the biofilm, and virulence-related genes was investigated. We confirmed that two lactic acid bacteria (LAB) strains isolated from plant sources, Lactiplantibacillus plantarum MSC-C2 and Pediococcus pentosaceus K40, secrete PLA into the de Man, Rogosa & Sharpe (MRS) broth when supplemented with phenyl pyruvic acid (PPA) as a precursor to PLA. Moreover, PLA was generated in the fermentation broths of two medicinal plant extracts, Paeonia lactiflora Pall (PR) and Carthamus tinctorius (CT), when used by each LAB strain and each extract supplemented with PPA. We determined that the minimum inhibitory concentration (MIC) of PLA against A. actinomycetemcomitans was 20 mM. PLA significantly decreased biofilm formation and suppressed the transcription of pgA, ltxA, and cdtB genes, which encode the poly-N-acetylglucosamine (PGA) polysaccharide of biofilm matrix and exotoxins leukotoxin and cytolethal distending toxin (CDT), respectively. The PLA produced by the MSC-C2 and K40 strains was increased several times by the addition of PPA to the MRS broth. The anti-biofilm effect of the extracts from the fermentation broth was proportional to the increasing PLA concentration, while a cumulatively higher effect than that of PLA alone suggested a combinational effect of PLA and the other metabolites, such as lactic acid (LA). Among the two medicinal plants, PLA, produced after the addition of PPA, was higher in PR extract in case of both the LAB strains. PLA production by the MSC-C2 strain in the PR extract reached 4.8 ± 0.23 mM, which was obviously higher than that in the MRS broth (3.88 ± 0.12 mM) supplemented with 1 mg/ml PPA. The activity to inhibit biofilm formation in the fermented PR extract was clearly high. PLA formed in the fermented PR extract downregulated the dispersin B encoding the dspB gene together with pgA, ltxA, and cdtB. In conclusion, this study shows a promising activity of PLA against the A. actinomycetemcomitans biofilm and virulence genes. In addition, the combinational effect of PLA and the medicinal plant extract can be achieved by fermentation with a specific plant-derived LAB strain.

Hypothalamic orexin prevents non-alcoholic steatohepatitis and hepatocellular carcinoma in obesity.

Non-alcoholic steatohepatitis (NASH) occasionally occurs under obesity; however, factors modulating the natural history of fatty liver disease remain unknown. Since hypothalamic orexin that regulates physical activity and autonomic balance prevents obesity, we investigate its role in NASH development. Male orexin-deficient mice fed a high-fat diet (HFD) show severe obesity and progression of NASH with fibrosis in the liver. Hepatic fibrosis also develops in ovariectomized orexin-deficient females fed an HFD but not ovariectomized wild-type controls. Moreover, long-term HFD feeding causes hepatocellular carcinoma (HCC) in orexin-deficient mice. Intracerebroventricular injection of orexin A or pharmacogenetic activation of orexin neurons acutely activates hepatic mTOR-sXbp1 pathway to prevent endoplasmic reticulum (ER) stress, a NASH-causing factor. Daily supplementation of orexin A attenuates hepatic ER stress and inflammation in orexin-deficient mice fed an HFD, and autonomic ganglionic blocker suppresses the orexin actions. These results suggest that hypothalamic orexin is an essential factor for preventing NASH and associated HCC under obesity.

Risk factors associated with hypoglycemic events after total pancreatectomy: A nationwide multicenter prospective study in Japan.

BACKGROUND: The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy. METHODS: Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study. RESULTS: Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period. CONCLUSION: Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.

Fermentation in Pineapple Juice Significantly Enhances Ornithine and Citrulline Production in Lactococcus lactis MSC-3G Isolated from Sugarcane.

Lactic acid bacterial (LAB) fermentation of functional amino acids using fruit juices as a cultivation medium is not well-documented. In the present study, we successfully isolated a high ornithine- and citrulline-producing Lactococcus lactis strain, designated MSC-3G, from sugarcane and investigated the ornithine and citrulline production profile using various fruit juices as a cultivation medium. Among fruit juices, pineapple juice exhibited the highest potentiality to initiate ornithine production (56 mM), while the highest citrulline yield was obtained during lime juice cultivation (34.5 mM). Under the optimal cultivation condition, the highest yield of ornithine and citrulline in pineapple juice reached 98.9 ± 2.2 mM and 211.1 ± 35.7 mM, respectively, both of which were significantly higher than that in the well-known industrial strain of Corynebacterium (C.) glutamicum. Additionally, citrulline production was dependent on oxygen supplementation and increased twofold when grown aerobically. Whole genome sequencing showed that the MSC-3G genome possesses the arginine deiminase (ADI) gene cluster arcABD1C1C2TD2. The results of the ADI pathway enzyme activities of MSC-3G showed a significant increase in arginine deiminase activity, while ornithine carbamoyl transferase activity was decreased, which in turn indicates the high citrulline-accumulation ability of MSC-3G when cultivated in pineapple juice.

Biomedical applications of L-alanine produced by Pediococcus acidilactici BD16 (alaD+).

L-alanine possesses extensive physiological functionality and tremendous pharmacological significance, therefore could be considered as potential ingredient for food, pharmaceutical, and personal care products. However, therapeutic properties of L-alanine still need to be addressed in detail to further strengthen its utilization as a viable ingredient for developing natural therapeutics with minimum side effects. Thus, the present study was aimed to explore the anticipated therapeutic potential of L-alanine, produced microbially using a lactic acid bacterial strain Pediococcus acidilactici BD16 (alaD+) expressing L-alanine dehydrogenase enzyme. The anticipated therapeutic potential of L-alanine was assessed in terms of anti-proliferative, anti-bacterial, and anti-urolithiatic properties. Anti-bacterial assays revealed that L-alanine successfully inhibited growth and in vitro proliferation of important human pathogens including Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, Streptococcus mutans, and Vibrio cholerae in a concentration-dependent manner. Current investigation has also revealed its significant anti-proliferative potential against human lung adenocarcinoma (A549; IC50 7.32 µM) and mammary gland adenocarcinoma (MCF-7; IC50 8.81 µM) cells. The anti-urolithiatic potential of L-alanine was augmented over three different phases, viz., nucleation inhibition, aggregation inhibition, and oxalate depletion. Further, an in vitro cell culture-based kidney stone dissolution model using HEK293-T cells was also established to further strengthen its anti-urolithiatic potential. This is probably the first in vitro cell culture-based model which experimentally validates the immense therapeutic efficacy of L-alanine in treating urolithiasis disease. KEY POINTS: • Assessment of therapeutic potential of L-alanine produced by LAB. • L-alanine exhibited significant anti-proliferative and anti-bacterial activities. • L-alanine as potential anti-urolithiatic agent.

Incidence and risk factors of nonalcoholic fatty liver disease after total pancreatectomy: A first multicenter prospective study in Japan.

BACKGROUND/PURPOSE: In the present study we aimed to prospectively assess the current prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) after total pancreatectomy (TP). METHODS: Between August 2015 and December 2017, we prospectively collected data from 68 Japanese centers on 148 consecutive patients who underwent TP whose computed tomography (CT) attenuation values were evaluated for 12 months. We defined post-TP NAFLD as a liver parenchyma CT value of less than 40 Hounsfield units (HU). Data on perioperative variables were retrieved from all patients and evaluated using univariate and multivariate analyses to identify the perioperative risk factors of NAFLD. RESULTS: In this prospective cohort study, supplementation of pancreatic exocrine enzymes was provided to all 148 patients, and 97% of them were treated with high-titer pancrelipase (median dosage: 1800 mg) postoperatively. Indeed, 29 patients (19.6%) developed NAFLD within a year after TP. Multivariate analysis revealed that female sex (P = .002), higher body mass index (BMI) (P = .001), and postoperative diarrhea (P = .038) were independent risk factors for post-TP NAFLD. However, post-TP NAFLD ameliorated in 11 patients (37.9%) at 12 months after surgery. CONCLUSIONS: Among patients with risk factors such as female sex, higher BMI, and postoperative diarrhea, attention should be paid to the occurrence of NAFLD after TP.

Exopolysaccharide Produced by Plant-Derived Lactobacillus plantarum SN35N Exhibits Antiviral Activity.

A lactic acid bacterial strain, Lactobacillus plantarum SN35N, which has been isolated from the pear, secretes negatively charged acidic exopolysaccharide (EPS) to outside cells. We have previously found that the SN35N-derived acidic EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.35) promoting inflammation. The aim of this study is to find other health benefits of EPS. EPS has been found to exhibit an inhibitory effect against the influenza virus (Alphainfluenzavirus Influenza A virus) and feline calicivirus (Vesivirus Feline calicivirus), which is recognized as a model of norovirus. Although more studies on the structure-function relationship of EPSs are needed, SN35N-derived EPS is a promising lead for developing not only anti-inflammatory agents, but also antiviral substances.

Plant-Derived Lactobacillus paracasei IJH-SONE68 Improves Chronic Allergy Status: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

We have recently demonstrated that the exopolysaccharides (EPSs) produced by a plant-derived lactic acid bacterium, Lactobacillus paracasei IJH-SONE68, prevent and ameliorate allergic reaction on contact in dermatitis model mice. In the present study, we conducted a clinical trial using a capsule containing spray-dried powder from pineapple juice broth fermented with the LAB strain as an experimental diet. The clinical trial was conducted as a double-blind and placebo-controlled randomized comparative study from May 2019 to July 2021. Males and females between the ages of 21 and 70 who experience chronic allergies participated in the study. Sixty subjects were instructed to orally take a capsule containing the IJH-SONE68 powder or placebo, every day for 12 weeks. After the clinical trial was over, the scores based on subjects' self-assessment of allergic status were significantly improved in the intervention group, as compared with the placebo group. Some serum biochemicals associated with inflammation response were also significantly improved by intake of the experimental diet. In conclusion, the IJH-SONE68-derived EPS improves chronic allergy status in humans and is expected to decrease their inconvenience.