Evaluation of Menopausal Syndrome Relief and Anti-Obesity Efficacy of the Korean Fermented Food Doenjang: A Randomized, Double-Blind Clinical Trial.

Foods that help improve menopausal syndrome are being studied worldwide. Doenjang is a traditional Korean fermented soybean food with potential health benefits for menopausal women. In this clinical trial using Doenjang, we aimed to compare the effectiveness of traditional Doenjang and commercial Doenjang in menopausal women. Furthermore, we compared whether Doenjang has a better effect if the number of beneficial microbes is higher. The analyses included the following groups: traditional Doenjang containing either a high dose (HDC; n = 18) or low dose (LDC; n = 18) of beneficial microbes and commercial Doenjang (CD; n = 20). The Kupperman index and hematological changes were examined before and after the use of Doenjang pills. The effects of Doenjang on obesity and body composition were studied before and after ingestion. Lastly, the microorganisms and short-chain fatty acid changes in the stool were compared. The Kupperman index decreased after Doenjang consumption in all three groups, with the greatest decrease in the LDC group. Only the groups that took traditional Doenjang pills exhibited reduced LDL cholesterol. No changes in obesity and inflammation-related indicators were observed. The number of Firmicutes, associated with obesity, decreased in the CD group but the numbers of Bacteroidetes increased in the HDC and CD groups. Thus, traditional Doenjang is more effective in alleviating menopausal syndrome than commercial Doenjang. Further research on the anti-obesity effect or changes in microbiomes and short-chain fatty acids in feces is needed.

Lactic acid bacteria-malted vinegar: fermentation characteristics and anti-hyperlipidemic effect.

In this study, the fermentation characteristics and functional properties of lactic acid bacteria-malted vinegar (LAB-MV) were investigated during the fermentation period. Changes in the components (organic acids, free sugars, free amino acids, ß-glucan, and gamma-aminobutyric acid (GABA)) of MV (BWAF0d, BWAF10d, BWAF20d) and LAB-MV (LBWAF0d, LBWAF10d, LBWAF20d) were analyzed according to the fermentation time. The amounts of ß-glucan and GABA in LBWAF20d were greater than those in BWAF20d (122.00 µg/mL, 83.06 µg/mL and 531.00 µg/mL, 181.31 µg/mL, respectively). The ACE1 and HMG-CoA reductase inhibitory activities of LBWAF20d were 98.16% (1/20 dilution factor, DF) and 91.01% (1/25 DF), respectively. The lipid accumulation ratio and total cholesterol levels in HepG2 cells treated with LBWAF20d (1/200 DF) were reduced by 45.85% and 54.48%, respectively, compared to those in the untreated group. These results suggest that LAB-MV, which comprises barley wine manufactured from LAB and yeast, may improve hepatic lipid metabolism.

Gochujang, a traditional Korean fermented food, protects through suppressed inflammatory pathways and histological structure disruption in dextran sodium sulfate (DSS)-induced colitis mice.

The mechanisms underlying chronic inflammatory diseases remain unclear. Therefore, researchers have explored the mechanisms underlying colitis using diverse materials. Recently, there has been an increasing interest in fermented products and bioconversion materials, their potential efficacy is being actively studied. Gochujang, a traditional Korean fermented product, is crafted by blending fermented Meju powder, gochu (Korean chili) powder, glutinous rice, and salt. In our study, we explored the effectiveness of Gochujang (500 mg/kg; Cheongju and Hongcheon, Korea) in dextran sulfate sodium (DSS)-induced colitis mice model. Gochujang was orally administered for 2 weeks, followed by the induction of colitis using 3% DSS in the previous week. During our investigation, Gochujang variants (TCG22-25, Cheongju and TCG22-48, Hongcheon) did not exhibit significant inhibition of weight reduction (p = 0.061) but notably (p = 0.001) suppressed the reduction in large intestine length in DSS-induced colitis mice. In the serum from colitis mice, TCG22-48 demonstrated reduced levels of the inflammatory cytokines interleukin (IL)-6 (p = 0.001) and tumor necrosis factor (TNF)-α (p = 0.001). Additionally, it inhibited the phosphorylation of Erk (p = 0.028), p38, and NF-κB (p = 0.001) the inflammatory mechanism. In our study, TCG22-25 demonstrated a reduction in the IL-6 level (p = 0.001) in serum and inhibited the phosphorylation of p38 and NF-κB (p = 0.001). Histological analysis revealed a significant (p = 0.001) reduction in the pathological score of the large intestine from TCG22-25 and TCG22-48. In conclusion, the intake of Gochujang demonstrates potent anti-inflammatory effects, mitigating colitis by preventing the large intestine length reduction of animals with colitis, lowering serum levels of TNF-α and IL-6 cytokines, and inhibiting histological disruption and inflammatory mechanism phosphorylation.

Evaluation of Body Changes and the Anti-Obesity Effect after Consumption of Korean Fermented Food, Cheonggukjang: Randomized, Double-Blind Clinical Trial.

Cheonggukjang is a traditional Korean fermented soybean food with potential health benefits. For this reason, Cheonggukjang is consumed in the form of pills in addition to being used as a food ingredient. There are few clinical studies that have evaluated changes in various health indicators through blood and stool tests before and after consumption of Cheonggukjang. In this study, symptoms and hematological changes were analyzed before and after the intake of traditional Cheonggukjang pills containing high-dose (n = 19) or low-dose (n = 20) beneficial bacteria and commercial Cheonggukjang pills (n = 20). Anti-obesity effects and body composition changes were determined before and after Cheonggukjang consumption. Lastly, the changes in microorganisms and short-chain fatty acids in the stool were compared. No changes in obesity and inflammation-related indicators were observed before and after Cheonggukjang consumption. The Firmicutes/Bacteroidetes ratio, associated with obesity, decreased in all three groups after Cheonggukjang consumption, but no statistical significance was indicated. Cheonggukjang contained various BAs, but they did not adversely affect symptoms and hematological changes in the participants. BAs generated during the manufacturing process of Cheonggukjang did not have any adverse effects in this randomized, double-blind clinical trial. Further research is needed in future concerning the anti-obesity effect or regarding changes in the microbiome and short-chain fatty acids in feces.

Improvement of Estrogen Deficiency Symptoms by the Intake of Long-Term Fermented Soybeans (Doenjang) Rich in Bacillus Species through Modulating Gut Microbiota in Estrogen-Deficient Rats.

Traditionally made doenjang (TMD) produced by the long-term fermentation of soybeans with salt may improve symptoms of estrogen deficiency. We aimed to evaluate the effects of four TMD types, containing low and high amounts of Bacillus species and biogenic amines (HBHA, HBLA, LBHA, and LBLA), on energy, glucose, and lipid metabolism, by altering the gut microbiota in estrogen-deficient ovariectomized (OVX) rats. Their mechanisms were also examined. The OVX rats were divided into the control, cooked soybean (CSB), HBHA, LBHA, HBLA, and LBLA groups. Sham-operated rats were the normal control group. Serum 17ß-estradiol concentrations were similar among all OVX groups. Tail skin temperatures, which are indicative of hot flashes, were higher in the control than the HBHA and HBLA groups and were similar to the normal control group. Weight gain and visceral fat mass were lower in the TMD and CSB intake groups but not as low as in the normal control group. Lean body mass showed a trend opposite to that of visceral fat in the respective groups. The hepatic triglyceride content decreased with the TMD intake compared to the control and CSB groups. mRNA expressions of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and carnitine palmitoyltransferase-1 in the TMD and CSB groups were as high as in the normal control group, and the PPAR-γ mRNA expression was more elevated in the HBLA group than in the normal control group. The morphology of the intestines improved in the TMD groups compared to the control, and the HBHA and HBLA groups showed an enhanced improvement compared to the CSB group. The HBHA, HBLA, and LBHA groups increased the α-diversity of the cecal microbiota compared to the control. Akkermenia and Lactobacillus were higher in the HBLA and LBLA groups compared to the control. The expression of the estrogen, forkhead box proteins of the class-O subgroup, and insulin-signaling pathways were lower in the control group, and HBHA and HBLA prevented their decrement. In conclusion, long-term treatment with TMD containing high amounts of Bacillus potentially improves estrogen deficiency symptoms more than unfermented soybeans.

Effects of Cheonggukjang (Fermented Soybean) on the Development of Colitis-Associated Colorectal Cancer in Mice.

Colorectal cancer (CRC) is the third most common type of cancer and is caused by multiple factors. Chronic inflammation, known to cause inflammatory bowel disease (IBD), is closely associated with CRC. Cheonggukjang (CJ), a traditional Korean fermented soybean, is a functional food with anti-inflammatory effects in the intestines, but its anti-cancer effects have not yet been explored. In this study, we investigated the cancer-protective effects of cheonggukjang in an azoxymethane/DSS (AOM/DSS)-induced colitis-associated colorectal cancer (CAC) mouse model. The CJ alleviated AOM/DSS-induced pathological symptoms such as colonic shortening, increased spleen weight, tumor formation, and histological changes. It also modulated pro-inflammatory and anti-inflammatory cytokine levels via the suppression of NF-κB and inflammatory mediator signaling pathways. Furthermore, the CJ improved intestinal integrity by regulating mucin-associated and tight junction proteins. In addition, it suppressed tumor growth by regulating apoptosis and proliferation. These results highlight the anti-tumor effects of CJ in an AOM/DSS-induced CAC mouse model.

Comparison of laxative effects of fermented soybeans (Cheonggukjang) containing toxins and biogenic amines against loperamide-induced constipation mouse model.

BACKGROUND/OBJECTIVES: Cheonggukjang is a traditional fermented soybean paste with significant health-promoting effects. On the other hand, there have been insufficient studies on the safety and efficacy of Cheonggukjang, which is produced using traditional methods containing toxins and biogenic amines (BAs). This study compared the laxative effect of Cheonggukjang, containing high or low levels of toxins and BAs (HTBC or LTBC) in a loperamide (Lop)-induced constipation mouse model. MATERIALS/METHODS: To induce constipation, Lop (5 mg/kg) was administered orally to ICR mice twice a day for 4 days, and the dose was increased to 8 mg/kg after a 3-day rest period. Cheonggukjang (500 mg/kg, HTBC, or LTBC respectively) was administered for four weeks before the Lop treatment. RESULTS: The number of stools, fecal weight, water contents, gastrointestinal transit, and histological alterations were recovered significantly in the HTBC or LTBC groups. HTBC and LTBC administration did not induce significant changes in body weight, dietary intake, and behavior. The opioid-receptor downstream signaling pathway in colon tissues was also evaluated. The c-Kit, stem cell kinase, and mitogen-activated protein kinases subfamilies, including extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinases, and p38, were all downregulated in the HTBC or LTBC-administered mice colon compared to the Lop group. CONCLUSION: These results show that Cheonggukjang, containing high levels of toxins and BAs, have a similar laxative effect in a mouse model of Lop-induced constipation.

Anti-Obesity Effects of Traditional and Commercial Kochujang in Overweight and Obese Adults: A Randomized Controlled Trial.

Kochujang shows anti-obesity effects in cell and animal models. Kochujang is traditionally prepared via slow fermentation or commercially using Aspergillus oryzae. We analyze the anti-obesity effects of two types of Kochujang in overweight and obese adults. The analyses included the following groups: traditional Kochujang containing either a high-dose (HTK; n = 19), or a low-dose of beneficial microbes (LTK; n = 18), and commercial Kochujang (CK; n = 17). Waist circumference decreased significantly in the HTK and CK groups. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels decreased in the HTK and LTK groups. Visceral fat is significantly reduced in the HTK group. The population of beneficial microorganisms in stool samples increased in all groups. Consumption of Kochujang reduces visceral fat content and improves the lipid profile, which can be enhanced by enrichment with beneficial microbes. These results suggest that Kochujang has the potential for application in obesity prevention.

Protective effect of traditional Korean fermented soybean foods (doenjang) on a dextran sulfate sodium-induced colitis mouse model.

Objective: The cause of ulcerative colitis (UC) is unknown, and the use of anti-inflammatory and immunosuppressive drugs with certain side effects is currently replacing treatment. Therefore, it is important to find new healthy foods or ingredients that exhibit potential protective and anti-inflammatory effects on UC. This study investigated the potential protective effect of doenjang on dextran sulfate sodium (DSS)-induced colitis in a mouse model. Materials and methods: Four doenjang samples (TCD21-51-1, TCD21-55-1, TMD21-16-1, and TFD21-1-1) were used. To examine the effects of the four doenjang samples on UC caused by DSS in a mouse model, the clinical symptoms of UC, such as body weight, disease activity index (DAI), and colon macroscopic damage index (CMDI) were analyzed. Moreover, immune-related blood cell counts, serum levels and protein expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and nitric oxide (NO) production were measured in DSS-induced UC in mice for analysis. Results: The four doenjang samples increased the colon length shortened by DSS, reduced DAI (diarrhea and hemoccult), CMDI (ulceration, inflammation, and hemorrhage) and the content of immune-related cells in the blood. Moreover, the levels of TNF-α, IL-6, and NO increased by DSS were decreased by doenjang, and tissue damage was significantly reduced. Conclusions: These findings confirmed that doenjang exerts protective effects against UC, suggesting its possible use in developing therapeutic strategies or functional products.

Protective Effects of Fermented Soybeans (Cheonggukjang) on Dextran Sodium Sulfate (DSS)-Induced Colitis in a Mouse Model.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease, and the incidence of IBD is increasing every year owing to changes in dietary structure. Although the exact pathogenesis of IBD is still unclear, recent evidence suggests that gut dysbiosis is closely associated with IBD pathogenesis. Cheonggukjang is a traditional Korean fermented soybean paste produced using traditional and industrial methods, and contains probiotics, which affect the gut microbiota composition. However, the protective effect of Cheonggukjang against IBD is unknown. In this study, we investigated the bacterial community structure of traditional and commercial Cheonggukjang samples, as well as the protective effect of Cheonggukjang on a dextran sulfate sodium (DSS)-induced colitis mouse model. Traditional and commercial Cheonggukjang were found to contain various type of useful probiotics in their bacterial community structure. Cheonggukjang reduced the progression of DSS-induced symptoms, such as body weight loss, colonic shortening, disease activity index, and histological changes. Further, Cheonggukjang improved the intestinal epithelial barrier integrity on DSS-induced colitis mice. In addition, Cheonggukjang suppressed the expression of proinflammatory cytokines and inflammatory mediators through the inactivation of NF-κB and MAPK signaling pathways. These results indicate that Cheonggukjang exerts protective effects against DSS-induced colitis, suggesting its possible application as a functional food for improving inflammatory diseases.

Biosorption of arsenite (As[III]) using Saccharomyces cerevisiae SRCM 501804 isolated from Korean turbid rice wine.

The potentiality of Saccharomyces cerevisiae SRCM 501804 to remove arsenite (As[III]) in an aqueous solution was investigated in this study. The S. cerevisiae SRCM 501804 was isolated from Korean turbid rice wine (Makgeolli). The S. cerevisiae SRCM 501804 was characterized by phylogenetic analysis, Fourier transform infrared (FT-IR) spectroscopy, visual minerals technologies (MINTEQ) model, and point of zero charge (pHpzc). The relationship between the factors (pH, biosorbent dosage, contact time, and concentration) and biosorption capacity was investigated. The S. cerevisiae SRCM 501804 was removed 31.1-90.1% of the As(III) depending on the initial biomass dosage within 1 h. Co-existing anions in aqueous solution showed a negative influence on the biosorption performance of As(III) in the order Cl- > NO3- > SO42- > CO32-. The results of isotherms and kinetics suggested the Langmuir (R2 > 0.95) and Pseudo-second order (R2 > 0.99) models fit well with the equilibrium experimental data. The maximum biosorption capacity (qm) of S. cerevisiae SRCM 501804 biomass for As(III) was found to be 113.9 mg/g from Langmuir isotherm. Based on the results, it can be concluded that the biomass of S. cerevisiae SRCM 501804 could be used as an effective bio-sorbent for As(III) biosorption in an aqueous solution.

Significance of LED lights in enhancing the production of vinegar using Acetobacter pasteurianus AP01.

Vinegar is a common food additive produced by acetic acid bacteria (AAB) during fermentation process. Low yield and long incubation time in conventional vinegar fermentation processes has inspired research in developing efficient fermentation techniques by the activation of AAB for acetic acid production. The present study intends to enhance vinegar production using acetic acid bacteria and light emitting diode (LED). A total of eight acetic acid bacteria were isolated from Korean traditional vinegar and assessed for vinegar production. Isolate AP01 exhibited maximum vinegar production and was identified as Acetobacter pasteurianus based on the 16S rRNA sequences. The optimum fermentation conditions for the isolate AP01 was incubation under static condition at 30 °C for 10 days with 6% initial ethanol concentration. Fermentation under red LED light exhibited maximum vinegar production (3.6%) compared to green (3.5%), blue (3.2%), white (2.2%), and non-LED lights (3.0%). Vinegar produced using red LED showed less toxicity to mouse macrophage cell line (RAW 264.7) and high inhibitory effects on nitric oxide and IL-6 production. The results confirmed that red LED light could be used to increase the yield and decrease incubation time in vinegar fermentation process.

Bacterial Community and Anti-Cerebrovascular Disease-Related Bacillus Species Isolated from Traditionally Made Kochujang from Different Provinces of Korea.

Traditionally made Kochujang (TMK) is a long-term fermented soybean and rice mixture with red pepper and salts. The ambient bacteria in rice straw and nutrient components of Kochujang influence the bacteria community. We aimed to investigate the bacterial composition and quality of TMK from different provinces of Korea: Chungcheung (CC), Jeolla (JL), Kyungsang (KS), and GeongGee plus Kangwon (GK) provinces, and Jeju island (JJ). Furthermore, Bacillus spp. isolated from TMK were studied to have anti-cerebrovascular disease activity and probiotic properties. Seventy-three TMK samples from different regions were collected to assess the biogenic amine contents, bacteria composition using next-generation methods, and bacterial functions using Picrust2. Bacillus spp. was isolated from the collected TMK, and their antioxidant, fibrinolytic, and angiotensin I conversion enzyme (ACE) inhibitory activities and probiotic properties were examined. KS TMK had lower sodium contents than the other TMK. There were no significant differences in histamine and tyramine contents among the TMK samples in different provinces. The predominant bacteria in TMK was Bacillus spp., but KS included much less Bacillus spp. and higher Enterococcus and Staphylococcus than the other TMK. Gene expression related to lipopolysaccharide biosynthesis was higher in KS TMK than the other TMK in Picrust2. The predominant Bacillus spp. isolated from TMK was B. subtilis and B. velezensis. B. subtilis SRCM117233, SRCM117245, and SRCM117253 had antioxidant activity, whereas B. subtilis had higher fibrinolytic activity than other Bacillus spp. Only B. velezensis SRCM117254, SRCM117311, SRCM117314, and SRCM117318 had over 10% ACE inhibitory activity. In conclusion, KS had less Bacillus related to lower sodium contents than the other TMK. The specific strains of B. subtilis and B. velezensis had antioxidant, fibrinolytic, and ACE inhibitory activity, and they can be used as a starter culture to produce better quality controlled Kochujang with anti-cerebrovascular disease activities.

Bacterial Distribution, Biogenic Amine Contents, and Functionalities of Traditionally Made Doenjang, a Long-Term Fermented Soybean Food, from Different Areas of Korea.

Since doenjang quality depends on the bacterial composition, which ambient bacteria in the environment and production conditions influence, a complete understanding of the bacteria community in traditionally madetraditionally made doenjang (TMD) from different regions is needed. We aimed to investigate the bacteria composition and quality of TMD in the following areas: Chonbuk (CB), Chonnam (CN), Kyungsang (KS), Kangwon (KW), Chungchung (CC) provinces, and Jeju island (JJ) of Korea. Twenty-nine TMD samples from different regions were used to assess biogenic amine contents, bacteria composition using next-generation methods, and metabolic functions of the bacteria using Picrust2. Bacillus spp. were isolated, and their antioxidant and fibrinolytic activities were determined. Most TMD contained high amounts of beneficial bacteria (Bacillus, Lactobacillus, Pediococcus and Weissella). However, some KS samples contained harmful bacteria (Cronobacter, Proteus and Acinetobacter) and less beneficial B. velezensis bacteria. There was no similarity among the regional groups, and each TMD showed a different bacteria composition. Shannon index, α-diversity index, was lower in TMD from JJ and CB than the other areas, but there was no ß-diversity among TMD from the six area groups. Picrust2 analysis revealed that the functional potential for arachidonic acid metabolism was lowest in JJ and CN, that for supporting insulin action was highest in KS and JJ, and that for carbohydrate digestion and absorption was lowest in CB and JJ among all groups (p < 0.05) according to the Kyoto Encyclopedia of Genes and Genomes Orthology. Histamine contents were lower in CN and CC, and tyramine contents did not differ significantly. B. velezensis, B. subtilis, B. licheniformis, B. siamensis, and B. amyloliquefaciens were isolated from TMD. None of the isolated Bacillus spp. contained the B. cereus gene. B. subtilis from CN had the highest fibrinolytic activity, and B. velezensis from CB had the highest antioxidant activity. In conclusion, TMD mainly contained various Bacillus spp., and the predominant one was B. velezensis, which had antioxidant and fibrinolytic activity regardless of the regional origin.

Bacillus amyloliquefaciens SCGB1 Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice Through Immune Regulation.

Probiotics, as living microorganisms, exert health benefits to the host by alleviating excess inflammation through modulating the immune system and establishing intestinal homeostasis. In this study, we evaluated the probiotic characteristics and inflammation alleviatory effects of Bacillus amyloliquefaciens isolated from traditional Korean fermented foods. The strains withstood the acidic environment of the digestive process, extended the lifespan of Caenorhabditis elegans, and enhanced pmk-1 expression. However, only B. amyloliquefaciens SCGB1 could attach to C. elegans in the intestines, which enhanced their survival upon exposure to Escherichia coli O157:H7. We also investigated the anti-inflammatory effect of SCGB1 using the RAW264.7 macrophage stimulated with lipopolysaccharide. The strain treatment enhanced anti-inflammatory cytokine interleukin (IL)-10 secretion and downregulated proinflammatory cytokine IL-6 expression in vitro. Next, we used a dextran sulfate sodium (DSS)-induced colitis mouse model to investigate whether SCGB1 can ameliorate gut inflammation in vivo. Compared to those in the DSS-induced mice, histological damage and IL-6 cytokine levels were significantly reduced in SCGB1-fed mice. These results suggest that B. amyloliquefaciens SCGB1 as potential probiotics may have health-promoting effects by reduction of inflammatory responses.

γ-PGA-Rich Chungkookjang, Short-Term Fermented Soybeans: Prevents Memory Impairment by Modulating Brain Insulin Sensitivity, Neuro-Inflammation, and the Gut-Microbiome-Brain Axis.

Fermented soybean paste is an indigenous food for use in cooking in East and Southeast Asia. Korea developed and used its traditional fermented foods two thousand years ago. Chungkookjang has unique characteristics such as short-term fermentation (24-72 h) without salt, and fermentation mostly with Bacilli. Traditionally fermented chungkookjang (TFC) is whole cooked soybeans that are fermented predominantly by Bacillus species. However, Bacillus species are different in the environment according to the regions and seasons due to the specific bacteria. Bacillus species differently contribute to the bioactive components of chungkookjang, resulting in different functionalities. In this review, we evaluated the production process of poly-γ-glutamic acid (γ-PGA)-rich chungkookjang fermented with specific Bacillus species and their effects on memory function through the modulation of brain insulin resistance, neuroinflammation, and the gut-microbiome-brain axis. Bacillus species were isolated from the TFC made in Sunchang, Korea, and they included Bacillus (B.) subtilis, B. licheniformis, and B. amyloliquefaciens. Chungkookjang contains isoflavone aglycans, peptides, dietary fiber, γ-PGA, and Bacillus species. Chungkookjangs made with B. licheniformis and B. amyloliquefaciens have higher contents of γ-PGA, and they are more effective for improving glucose metabolism and memory function. Chungkookjang has better efficacy for reducing inflammation and oxidative stress than other fermented soy foods. Insulin sensitivity is improved, not only in systemic organs such as the liver and adipose tissues, but also in the brain. Chungkookjang intake prevents and alleviates memory impairment induced by Alzheimer's disease and cerebral ischemia. This review suggests that the intake of chungkookjang (20-30 g/day) rich in γ-PGA acts as a synbiotic in humans and promotes memory function by suppressing brain insulin resistance and neuroinflammation and by modulating the gut-microbiome-brain axis.

Probiotic Lactobacillus fermentum strain JDFM216 improves cognitive behavior and modulates immune response with gut microbiota.

Increasing evidence indicates that alterations in gut microbiota are associated with mammalian development and physiology. The gut microbiota has been proposed as an essential player in metabolic diseases including brain health. This study aimed to determine the impact of probiotics on degenerative changes in the gut microbiota and cognitive behavior. Assessment of various behavioral and physiological functions was performed using Y-maze tests, wheel running tests, accelerated rotarod tests, balance beam tests, and forced swimming tests (FSTs), using adult mice after 50 weeks of administering living probiotic bacterium Lactobacillus fermentum strain JDFM216 or a vehicle. Immunomodulatory function was investigated using immune organs, immune cells and immune molecules in the mice, and gut microbiota was also evaluated in their feces. Notably, the L. fermentum JDFM216-treated group showed significantly better performance in the behavior tests (P < 0.05) as well as improved phagocytic activity of macrophages, enhanced sIgA production, and stimulated immune cells (P < 0.05). In aged mice, we observed decreases in species belonging to the Porphyromonadaceae family and the Lactobacillus genus when compared to young mice. While administering the supplementation of L. fermentum JDFM216 to aged mice did not shift the whole gut microbiota, the abundance of Lactobacillus species was significantly increased (P < 0.05). Our findings suggested that L. fermentum JDFM216 also provided beneficial effects on the regulation of immune responses, which has promising implications for functional foods. Taken together, L. fermentum JDFM216 could confer the benefit of improving health with enhanced cognition, physiological behavior, and immunity by modulating the gut microbiota.

Comparative Genomic and Functional Evaluations of Bacillus subtilis Newly Isolated from Korean Traditional Fermented Foods.

Many fermented foods are known to have beneficial effects on human and animal health, offering anti-aging and immunomodulatory benefits to host. Microorganisms contained in the fermented foods are known to provide metabolic products possibly improving host health. However, despite of a number of studies on the functional effects of the fermented foods, isolation and identification of the effective bacterial strains in the products are still in progress. The objective of this study was to isolate candidate functional strains in various Korean traditional fermented foods, including ganjang, gochujang, doenjang, and jeotgal, and evaluate their beneficial effects on the host, using Caenorhabditis elegans as a surrogate animal model. Among the 30 strains isolated, five Bacillus spp. were selected that increased the expression level of pmk-1, an innate immune gene of C. elegans. These strains extended the nematode lifespan and showed intestinal adhesion to the host. Based on the bioinformatic analyses of whole genome sequences and pangenomes, the five strains of Bacillus subtilis were genetically different from the strains found in East Asian countries and previously reported strains isolated from Korean fermented foods. Our findings suggest that the newly isolated B. subtilis strains can be a good candidate for probiotic with further in-depth investigation on health benefits and safety.

Pediococcus acidilactici intake decreases the clinical severity of atopic dermatitis along with increasing mucin production and improving the gut microbiome in Nc/Nga mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with intestinal microflora. Since specific probiotics may have better efficacy for AD, we determined the efficacy of Pediococcus acidilactici SRCM102024 (PA) for treating AD in HaCaT cells and NC/Nga mice and explored the mechanism of action. AD-like pathology was induced in HaCaT cells and the dorsal skin of Nc/Nga mice by local exposure to 2,4-dinitrochlorobenzene (DNCB). In AD-lesion induced mice, PA in low-, medium- and high-dosages (5 × 10E6, 5 × 10E7 and 5 × 10E8 CFU/kg bw, respectively) and dexamethasone (3 mg/kg bw, positive-control) were orally administered for 5 weeks. The clinical AD severity, serum immunoglobulin E (IgE) and TNF-α, gene expressions of interleukin (IL)-4, IL-13, and TNF-α and gut microflora were measured. PA treatment (100-300 CFU/mL) dose-dependently increased cell survival in DNCB-induced HACAT cells. PA reduced the relative mRNA expression of PAR-2, TNF-α, IL-4 and IL-13 in the cells. In dorsal skin of Nc/Nga mice applied with DNCB, PA dose-dependently attenuated erythema, hemorrhage, edema, excoriation, dryness and scratching behavior and PA-H improved the clinical symptoms similar to the positive-control. PA-M and PA-H treatment significantly prevented the disturbance of the dorsal skin tissues and decreased the inflammatory cellular infiltrate of mast cells, compared to the control. PA dose-dependently reduced serum IgE and TNF-α concentrations and the mRNA expression of TNF-α, IL-4, and IL-13 in dorsal skin. In gut microflora, relative counts of Lactobacillales, Butyricicoccus and Ruminococcus were decreased in the AD-control compared to the positive-control and the PA-M and PA-H prevented their decrease. However, the positive-control increased serum AST and ALT activities, indicating liver damage as an adverse effect. In conclusion, oral treatment of PA (human equivalent 1 × 10E9-1 × 10E10) relieved the AD symptoms by dose-dependently preventing over-activation of the immune response. Oral PA intake may be a safe and effective alternative therapy for AD.

A randomized, double-blind, placebo-controlled crossover clinical trial to evaluate the anti-diabetic effects of Allium hookeri extract in the subjects with prediabetes.

BACKGROUND: Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia. A. hookeri has been reported anti-inflammatory, anti-obesity, osteoblastic, anti-oxidant, and anti-diabetic effects in animal studies. We investigated the anti-diabetic effects of A. hookeri aqueous extract (AHE) in the Korean subjects. METHODS: Prediabetic subjects (100 ≤ fasting plasma glucose (FPG) < 126 mg/dL) who met the inclusion criteria were recruited for this study. The enrolled subjects (n = 30) were randomly divided into either an AHE (n = 15, 486 mg/day) or placebo (n = 15) group. Outcomes were measurements of FPG, glycemic response to an oral glucose tolerance test (OGTT), insulin, C-peptide, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol. The t-test was used to assess differences between the groups. A p-value < 0.05 was considered statistically significant. RESULTS: Eight weeks after AHE supplementation, HbA1c level was significantly decreased in the AHE group compared with the placebo group. No clinically significant changes in any safety parameter were observed. CONCLUSION: The findings suggest that AHE can be effective in reducing HbA1c, indicating it as an adjunctive tool for improving glycemic control. TRIAL REGISTRATION: The study protocol was retrospectively registered at www.clinicaltrials.gov ( NCT03330366 , October 30, 2017).