The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes—IL-17A, IRF4, RORC, IL-21, and IL-23R—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.

Background: To evaluate the immunomodulatory effect of Lactobacillus sakei in a mouse model of rheumatoid arthritis (RA) and in human immune cells. Methods: We evaluated whether L. sakei reduced the severity of collagen-induced arthritis (CIA) and modulated interleukin (IL)-17 and IL-10 levels, as well as whether it affected the differentiation of CD4 + T cells and regulatory B cells. We evaluated osteoclastogenesis after culturing bone marrow-derived mononuclear cells with L. sakei. Results: The differentiation of T helper 17 cells and the serum level of IL-17 were suppressed by L. sakei in both human peripheral blood mononuclear cells and mouse splenocytes. The serum level of IL-10 was significantly increased in the L. sakei -treated group, whereas the regulatory T cell population was unchanged. The population of regulatory B cells significantly increased the in L. sakei -treated group. Oral administration of L. sakei reduced the arthritis incidence and score in mice with CIA. Finally, osteoclastogenesis and the mRNA levels of osteoclast-related genes were suppressed in the L. sakei -treated group. Conclusion: L. sakei exerted an anti-inflammatory effect in an animal model of RA, regulated Th17 and regulatory B cell differentiation, and suppressed osteoclastogenesis. Our findings suggest that L. sakei has therapeutic potential for RA.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints and extra-articular manifestations. Recent studies have shown that microorganisms affect RA pathogenesis. However, few studies have examined the microbial distribution of early RA patients, particularly female patients. In the present study, we investigated the gut microbiome profile and microbial functions in early RA female patients, including preclinical and clinically apparent RA cases. Changes in microbiological diversity, composition, and function in each group were analyzed using quantitative insights into microbial ecology (QIIME) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The results revealed the dysbiosis due to decreased diversity in the early RA patients compared with healthy subjects. There were significant differences in the microbial distribution of various taxa from phylum to genus levels between healthy subjects and early RA patients. Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus Collinsella, was enriched in healthy subjects. Functional analysis based on clusters of orthologous groups revealed that the genes related to the biosynthesis of menaquinone, known to be derived from gram-positive bacteria, were enriched in healthy subjects, while iron transport-related genes were enriched in early RA patients. Genes related to the biosynthesis of lipopolysaccharide, the gram-negative bacterial endotoxin, were enriched in clinically apparent RA patients. The obvious differences in microbial diversity, taxa, and associated functions of the gut microbiota between healthy subjects and early RA patients highlight the involvement of the gut microbiome in the early stages of RA.

A total of 57 infants hospitalized with rotavirus disease were included in this study. The children were randomly divided into the study’s two treatment groups: three days of the oral administration of (i) a probiotics formula containing both Bifidobacterium longum BORI and Lactobacillus acidophilus AD031 (N = 28); or (ii) a placebo (probiotic-free skim milk, N = 29) and the standard therapy for diarrhea. There were no differences in age, sex, or blood characteristics between the two groups. When the 57 cases completed the protocol, the duration of the patients’ diarrhea was significantly shorter in the probiotics group (4.38 ± 1.29, N = 28) than the placebo group (5.61 ± 1.23, N = 29), with a p-value of 0.001. Symptoms such as duration of fever (p = 0.119), frequency of diarrhea (p = 0.119), and frequency of vomiting (p = 0.331) tended to be ameliorated by the probiotic treatment; however, differences were not statistically significant between the two groups. There were no serious, adverse events and no differences in the frequency of adverse events in both groups.

OBJECTIVES:This work aimed to compare some pharmacological properties of red ginseng extract (RG) and fermented red ginseng extract (FRG).METHODS:Antinociceptive activity was analysed using the acetic acid-induced abdominal constriction response. Anti-inflammatory activity was evaluated using acetic acid-induced vascular permeability and carrageenan-induced inflammation in the air pouch, and analysed through the measurement of nitrite content in the lipopolysaccharide (LPS)-stimulated macrophage cells. Anti-angiogenic activity was determined using the chick chorioallantoic membrane assay.KEY FINDINGS:In-vivo anti-inflammatory activity of FRG was stronger than that of RG in two animal models, vascular permeability and air-pouch models. In the vascular permeability model, the doses of RG and FRG required for half-maximal inhibition (IC50) were 181 and 59mg/kg, respectively. FRG exhibited significantly stronger antinociceptive activity than RG. In the acetic acid-induced abdominal constriction response, the IC50 values of RG and FRG were 153 and 27mg/kg, respectively. Although both RG and FRG were able to suppress production of nitric oxide in the LPS-stimulated RAW264.7 macrophage cells, the suppressive activity of FRG appeared to be stronger than that of RG. However, RG and FRG showed similar anti-angiogenic activity.CONCLUSIONS:FRG possesses enhanced anti-inflammatory and antinociceptive activity but similar anti-angiogenic activity than RG.

Bifidobacterium adolescentis Int57 (Int57) and Propionibacterium freudenreichii subsp. shermanii ATCC 13673 (ATCC 13673) were grown either in coculture or as pure cultures in different media, such as cow's milk, soybean milk, and modified MRS medium. The viable cell counts of bacteria, changes in pH, concentrations of organic acids, and contents of various sugars were analyzed during incubation up to 7days. In soy milk, the survival of cocultured Int57 was six times higher than the monocultured cells, and ATCC 13673 cocultured with Int57 consumed 69.4% of lactic acid produced by Int57 at the end of fermentation. In cow's milk, coculture with ATCC 13673 increased the growth of Int57 from 24h until 120h by approximately tenfold and did not affect the survival of Int57 cells. After 96h of fermentation of modified MRS, the survival of ATCC 13673 cells cocultured with Int57 increased by 3.2- to 7.4-folds as compared with ATCC 13673 monoculture, whereas the growth of Int57 cells was unaffected. The growth and metabolic patterns of two strains during coculture showed noticeable differences between food grade media and laboratory media. The consumption of stachyose in soy milk during coculture of Int57 with ATCC 13673 was increased by more than twice compared with Int57 monoculture, and completed within 24h. The combinational use of Bifidobacterium and Propionibacterium could be applied to the development of fermented milk or soy milk products.

Water extracts of eighteen herbal materials and genistein were used to investigate their effects on compound 48/80-induced histamine release in rat peritoneal mast cells (RPMCs). The inhibition effects of histamine release by the water extracts of Ulmus pumila Linne (UP), Lonicera japonica Thunberg (LJT), Angelica gigas Nakai (AGN), Cordyceps militaris (CM), Rehmannia glutinosa Liboschitz (RGL), Liriope platyphylla Wang et Tang (LPWT), Zizyphus jujuba var. inermis Rehder (ZJ) were evaluated by a dose-response assay. LPWT, ZJ, and genistein showed dose-dependent decrease in histamine release at the concentrations of 1 to 1,000 mg/mL, and the inhibition percentage reached up to 31.0, 35.9, and 46.2%, respectively. UP, LJT, AGN, CM, and RGL significantly decreased histamine release at 1 to 100 μg/mL. Among the various combinations, mixture of UP and genistein showed an enhanced inhibition on histamine release.

Garlic has been used for condiments and also for medicines to cure various diseases since ancient times. Many studies on the processing of garlic have been published, however, few of them were related with fermentation because of the antimicrobial action of the garlic. In this study, to conduct garlic fermentation, 4 lactic acid bacteria (LAB) strains with growth abilities in garlic medium were selected. Addition of various nitrogen, carbon, and mineral sources generally did not improve the growth of experimental strains during garlic fermentation except for Lactobacillus casei KFRI 704 by yeast extract and Lactococcus lactis subsp. cremoris ATCC 19257 by mineral sources. High performance liquid chromatography (HPLC) analysis of 32 phenolic compounds during fermentation showed that formononetin was decreased time dependently. The concentrations of volatile compounds and alliin did not change during fermentation. The results of this study would provide the basic understanding of garlic fermentation by selected strains of LAB.

Ginsenosides are responsible for the pharmacological and biological activities of ginseng. In this study, ginsenoside Rh1 and compound K were isolated and purified from fermented ginseng substrate and their anti-allergic effects were assessed in compound 48/80-induced anaphylactic shock model. The fermented ginseng substrate was extracted by methanol and ginsenoside Rh1 and compound K were efficiently purified by preparative high performance liquid chromatography (prep HPLC). Their quality and quantity were analyzed by liquid chromatography-mass spectrometer (LC-MS) and HPLC. Ginsenoside Rh1 showed better anti-allergic effects than compound K in compound 48/80-induced anaphylactic shock model, This study suggested that fermented ginseng extracts with enriched Rh1 may be utilized as a potential biomaterial of functional food for the alleviation of allergic symptoms.

We have constructed a constitutive high-level-expression vector for the genus Bifidobacterium and used it to express cholesterol oxidase from Streptomyces coelicola. The promoter region of the 16S rRNA gene was amplified by inverse PCR and used for the construction of pBES16PR. The optimal ribosome-binding site (RBS) for Bifidobacterium was incorporated in pBES16PR. In order to test the efficacy of this expression vector, we constructed pBES16PR-CHOL with the structural gene for cholesterol oxidase under the control of the 16S rRNA promoter, and used it to transform Bifidobacterium longum. The gene was successfully expressed and high level of cholesterol oxidase activity was obtained in B. longum. This is the first report of an expression vector for the genus Bifidobacterium using a 16S rRNA gene promoter and successful expression of cholesterol oxidase.