The role of Bifidobacterium in longevity and the future of probiotics.

This review explores the role and health impacts of probiotics, focusing specifically on Bifidobacterium spp. It highlights the functionalities that Bifidobacteria can provide, underscored by the historical evolution of definitions and technological advancements related to probiotics. By examining the association between Bifidobacteria and longevity, this review suggests new avenues for health enhancement. Highlighting case studies of centenarians, it presents examples related to human aging, illuminating the potential links to longevity through research on Bifidobacterium strains found in centenarians. This review not only emphasizes the importance of current research but also advocates for further investigation into the health benefits of Bifidobacteria, underlining the necessity for continuous study in the nutraceutical field.

Investigating human-derived lactic acid bacteria for alcohol resistance.

BACKGROUND: Excessive alcohol consumption has been consistently linked to serious adverse health effects, particularly affecting the liver. One natural defense against the detrimental impacts of alcohol is provided by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), which detoxify harmful alcohol metabolites. Recent studies have shown that certain probiotic strains, notably Lactobacillus spp., possess alcohol resistance and can produce these critical enzymes. Incorporating these probiotics into alcoholic beverages represents a pioneering approach that can potentially mitigate the negative health effects of alcohol while meeting evolving consumer preferences for functional and health-centric products. RESULTS: Five lactic acid bacteria (LAB) isolates were identified: Lactobacillus paracasei Alc1, Lacticaseibacillus rhamnosus AA, Pediococcus acidilactici Alc3, Lactobacillus paracasei Alc4, and Pediococcus acidilactici Alc5. Assessment of their alcohol tolerance, safety, adhesion ability, and immunomodulatory effects identified L. rhamnosus AA as the most promising alcohol-tolerant probiotic strain. This strain also showed high production of ADH and ALDH. Whole genome sequencing analysis revealed that the L. rhamnosus AA genome contained both the adh (encoding for ADH) and the adhE (encoding for ALDH) genes. CONCLUSIONS: L. rhamnosus AA, a novel probiotic candidate, showed notable alcohol resistance and the capability to produce enzymes essential for alcohol metabolism. This strain is a highly promising candidate for integration into commercial alcoholic beverages upon completion of comprehensive safety and functionality evaluations.

Altered gut microbiome plays an important role in AKI to CKD transition in aged mice.

Introduction: This study investigated the role of renal-intestinal crosstalk in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) in elderly individuals. Methods: Using young and aged mice, we induced bilateral ischemia-reperfusion injury (IRI) and compared intestinal and kidney inflammation over 28 days. To determine the role of the microbiome in gut-kidney crosstalk, we analyzed the microbiome of fecal samples of the young vs. aged mice and examined the effects of probiotic supplementation. Results: In the post-IRI recovery phase, prolonged intestinal and renal inflammation along with dysbiosis were evident in aged vs. younger mice that was associated with severe renal dysfunction and fibrosis progression in aged mice. Probiotic supplementation with Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI alleviated intestinal inflammation but not intestinal leakage, characterized by decreased inflammatory cytokine levels and decreased infiltration of macrophages, neutrophils, and Th17 cells. This was associated with improved M1-dominant renal inflammation and ultimately improved renal function and fibrosis, suggesting that renal-intestinal crosstalk in aged mice contributes to the transition from AKI to CKD. Discussion: Our study findings suggest that exacerbation of chronic inflammation through the gut-kidney axis might be an important mechanism in the transition from AKI to CKD in the elderly.

Faecalibacterium prausnitzii alleviates inflammatory arthritis and regulates IL-17 production, short chain fatty acids, and the intestinal microbial flora in experimental mouse model for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease that leads to joint destruction and functional disability due to the targeting of self-antigens present in the synovium, cartilage, and bone. RA is caused by a number of complex factors, including genetics, environment, dietary habits, and altered intestinal microbial flora. Microorganisms in the gut bind to nod-like receptors and Toll-like receptors to regulate the immune system and produce various metabolites, such as short-chain fatty acids (SCFAs) that interact directly with the host. Faecalibacterium prausnitzii is a representative bacterium that produces butyrate, a well-known immunomodulatory agent in the body, and this microbe exerts anti-inflammatory effects in autoimmune diseases. METHODS: In this study, F. prausnitzii was administered in a mouse model of RA, to investigate RA pathology and changes in the intestinal microbial flora. Using collagen-induced arthritic mice, which is a representative animal model of RA, we administered F. prausnitzii orally for 7 weeks. RESULTS: The arthritis score and joint tissue damage were decreased in the mice administered F. prausnitzii compared with the vehicle-treated group. In addition, administration of F. prausnitzii reduced the abundance of systemic immune cells that secrete the pro-inflammatory cytokine IL-17 and induced changes in SCFA concentrations and the intestinal microbial flora composition. It also resulted in decreased lactate and acetate concentrations, an increased butyrate concentration, and altered compositions of bacteria known to exacerbate or improve RA. CONCLUSION: These results suggest that F. prausnitzii exerts a therapeutic effect on RA by regulation of IL-17 producing cells. In addition, F. prausnitzii modify the microbial flora composition and short chain fatty acids in experimental RA mouse model.

Bifidobacterium longum BORI inhibits pain behavior and chondrocyte death, and attenuates osteoarthritis progression.

Osteoarthritis (OA), the most common form of arthritis, is characterized by pain and cartilage damage; it usually exhibits gradual development. However, the pathogenesis of OA remains unclear. This study was undertaken to improve the understanding and treatment of OA. OA was induced in 7-week-old Wistar rats by intra-articular injection of monosodium iodoacetate (MIA); subsequently, the rats underwent oral administration of Bifidobacterium longum BORI (B. BORI). The effects of B. BORI were examined in chondrocytes and an MIA-induced OA rat model. In the rats, B. BORI-mediated effects on pain severity, cartilage destruction, and inflammation were recorded. Additional effects on mRNA and cytokine secretion were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Paw withdrawal threshold, paw withdrawal latency, and weight-bearing assessments revealed that pain severity in MIA-induced OA rats was decreased after B. BORI treatment. Histopathology analyses and three-dimensional surface renderings of rat femurs from micro-computed tomography images revealed cartilage protection and cartilage loss inhibition effects in B. BORI-treated OA rats. Immunohistochemical analyses of inflammatory cytokines and catabolic markers (e.g., matrix metalloproteinases) showed that the expression levels of both were reduced in tissue from B. BORI-treated OA rats. Furthermore, B. BORI treatment decreased the expression levels of the inflammatory cytokine monocyte chemoattractant protein-1 and inflammatory gene factors (e.g., inflammatory cell death markers) in chondrocytes. The findings indicate that oral administration of B. BORI has therapeutic potential in terms of reducing pain, progression, and inflammation in OA.

Peptoniphilus gorbachii alleviates collagen-induced arthritis in mice by improving intestinal homeostasis and immune regulation.

Introduction: The intricate connection between gut microbiota and rheumatoid arthritis (RA) pathogenesis has gained prominence, although the specific microbial species contributing to RA development remain largely unknown. Recent studies have sought to comprehensively explore alterations in the human microbiome, focusing on identifying disease-related microbial species through blood analysis. Consequently, this study aimed to identify RA-associated microbial species using a serum microbial array system and to investigate the efficacy and underlying mechanisms of potential microbial species for RA treatment. Methods: Serum immunoglobulin M levels against 384 intestinal microbial species were assessed using a microbial microarray in patients with RA and healthy individuals. We investigated the therapeutic potential of the identified microbial candidate regarding arthritis development, immune responses, gut barrier function, and gut microbiome using a collagen-induced arthritis (CIA) mouse model. Results: Our findings revealed significant alterations in antibody levels against 36 microbial species in patients with RA compared to healthy individuals. Notably, the antibody levels against Peptoniphilus gorbachii (PG) were decreased in patients with RA and exhibited an inverse correlation with RA disease activity. In vitro experiments demonstrated that PG produced acetate and butyrate, while exhibiting anti-inflammatory properties. In CIA mice, PG administration suppressed arthritis symptoms, reduced the accumulation of inflammatory monocytes in the mesenteric lymph nodes, and downregulated gene expression of pro-inflammatory cytokines in the ileum. Additionally, PG supplementation restored intestinal barrier integrity and partially resolved gut microbial dysbiosis in CIA mice. The fecal microbiota in PG-treated mice corresponded to improved intestinal barrier integrity and reduced inflammatory responses. Conclusion: This study highlights the potential of serum-based detection of anti-microbial antibodies to identify microbial targets at the species level for RA treatment. Moreover, our findings suggest that PG, identified through the microbial microarray analysis, holds therapeutic potential for RA by restoring intestinal barrier integrity and suppressing the immunologic response associated with RA.

In vivo functional effects of Weissella confusa VP30 exopolysaccharides on loperamide-induced constipation in rats.

In this work, the in vivo functionalities of milk fermented with Weissella confusa VP30 (VP30-EPS) and purified exopolysaccharide (pEPS) from the milk fermented with Weissella confusa VP30 were evaluated for their effect on constipation using an experimental constipated rat model. Rats were randomly divided into four groups: (i) control group (PBS administered normal group), (ii) loperamide treated group (constipation group), (iii) constipation with loperamide plus VP30-EPS (1 g/kg), and (iv) constipation with loperamide plus pEPS (0.6 g/kg) groups. Loperamide treatment induced animal constipation and significantly reduced the frequency of defecation, intestinal transit ratio, and water content of feces. However, all four fecal parameters were improved in both the loperamide plus VP30-EPS and pEPS administered groups as compared to the loperamide group. These results suggest that the addition of VP30-EPS potentially improves the functional laxative effects of commercial products. This study suggests the possibility that VP30-EPS can be applied to fermented and/or functional foods to relieve constipation.

A decrease in functional microbiomes represented as Faecalibacterium affects immune homeostasis in long-term stable liver transplant patients.

ABBREVIATIONS: LT, liver transplantation; HCC, hepatocellular carcinoma; IS, immunosuppressants; DC, dendritic cells; Treg, regulatory T; Th17, T helper 17; AST, aspartate transaminase; ALT, alanine transaminase; OUT, operational taxonomic unit; LEfSe, linear discriminant analysis effect size; LDA, linear discriminant analysis; IL, interleukin; TGF, transforming growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; TNF-α, tumor necrosis factor-α; MIP-1α, macrophage inflammatory protein-1α; IP-10, interferon γ-induced protein; MCP-1, monocyte chemoattractant protein-1; ACR, acute cellular rejection; NF-κB, nuclear factor κB; PT INR, prothrombin time; QC, quality check; PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay.

A recombinant Bifidobacterium bifidum BGN4 strain expressing the streptococcal superoxide dismutase gene ameliorates inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a gastrointestinal disease characterized by diarrhea, rectal bleeding, abdominal pain, and weight loss. Recombinant probiotics producing specific proteins with IBD therapeutic potential are currently considered novel drug substitutes. In this study, a Bifidobacterium bifidum BGN4-SK strain was designed to produce the antioxidant enzymes streptococcal superoxide dismutase (SOD) and lactobacillus catalase (CAT), and a B. bifidum BGN4-pBESIL10 strain was proposed to generate an anti-inflammatory cytokine, human interleukin (IL)-10. In vitro and in vivo efficacy of these genetically modified Bifidobacterium strains were evaluated for colitis amelioration. RESULTS: In a lipopolysaccharide (LPS)-stimulated HT-29 cell model, tumor necrosis factor (TNF)-α and IL-8 production was significantly suppressed in the B. bifidum BGN4-SK treatment, followed by B. bifidum BGN4-pBESIL10 treatment, when compared to the LPS-treated control. Synergistic effects on TNF-α suppression were also observed. In a dextran sodium sulphate (DSS)-induced colitis mouse model, B. bifidum BGN4-SK treatment significantly enhanced levels of antioxidant enzymes SOD, glutathione peroxidase (GSH-Px) and CAT, compared to the DSS-only group. B. bifidum BGN4-SK significantly ameliorated the symptoms of DSS-induced colitis, increased the expression of tight junction genes (claudin and ZO-1), and decreased pro-inflammatory cytokines IL-6, IL-1ß and TNF-α. CONCLUSIONS: These findings suggest that B. bifidum BGN4-SK ameliorated DSS-induced colitis by generating antioxidant enzymes, maintaining the epithelial barrier, and decreasing the production of pro-inflammatory cytokines. Although B. bifidum BGN4-pBESIL10 exerted anti-inflammatory effects in vitro, the enhancement of IL-10 production and alleviation of colitis were very limited.

Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI promotes neuronal rejuvenation in aged mice.

An increasing number of studies have indicated that alterations in gut microbiota affect brain function, including cognition and memory ability, via the gut-brain axis. In this study, we aimed to determine the protective effect of Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) on age-related brain damage in mice. We found that administration of B. bifidum BGN4 and B. longum BORI effectively elevates brain-derived neurotrophic factor expression which was mediated by increased histone 3 lysine 9 trimethylation. Furthermore, administration of probiotic supplementation reversed the DNA damage and apoptotic response in aged mice and also improved the age-related cognitive and memory deficits of these mice. Taken together, the present study highlights the anti-aging effects of B. bifidum BGN4 and B. longum BORI in the aged brain and their beneficial effects for age-related brain disorders.

Antibacterial effect of cell-free supernatant fraction from Lactobacillus paracasei CH88 against Gardnerella vaginalis.

Bacterial vaginosis (BV) is the most common vaginal infection in reproductive women, which is characterized by depleted level of lactic acid bacteria and overgrowth of anaerobes such as Gardnerella vaginalis spp. Lactic acid bacteria have been known to be beneficial for amelioration of BV, since they produce antimicrobial substances against G. vaginalis spp. The objectives of this study were to characterize different fractions of cell-free supernatant of Lactobacillus paracasei CH88 (LCFS) and investigate antibacterial activity of the LCFS fractions against G. vaginalis in-vitro and in-vivo. Antibacterial activity of the LCFS was stable during thermal treatment up to 120 °C for 30 min and maintained at pH ranging from 3.0 to 13.0 except pH 5.0. Fraction below 3 kDa of the LCFS partially lost its antibacterial activity after treatment with proteolytic enzymes. Precipitated protein fraction below 3 kDa of the LCFS (< 3 kDa LCFSP) inhibited the growth and biofilm formation of G. vaginalis. Treatment of L. paracasei CH88 or the < 3 kDa LCFSP attenuated G. vaginalis-induced BV in mice by inhibiting the growth of G. vaginalis, reducing exfoliation of vaginal epithelial cells, and regulating immune response. These results suggest that L. paracasei CH88 may have potential in ameliorating G. vaginalis-induced BV.

Bifidobacterium bifidum BGN4 Paraprobiotic Supplementation Alleviates Experimental Colitis by Maintaining Gut Barrier and Suppressing Nuclear Factor Kappa B Activation Signaling Molecules.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are characterized by chronic gastrointestinal inflammation with continuous relapse-remission cycles. This study aimed to evaluate the protective effect of Bifidobacterium bifidum BGN4 as a probiotic or paraprobiotic against dextran sulfate sodium (DSS)-induced colitis in mice. Ten-week-old female BALB/c mice were randomly divided into five groups. The control (CON) and DSS groups received oral gavage of PBS, whereas the live B. bifidum (LIVE), heat-killed B. bifidum BGN4 (HEAT), and lysozyme-treated B. bifidum BGN4 (LYSOZYME) groups received live B. bifidum BGN4, heat-killed B. bifidum BGN4, and lysozyme-treated B. bifidum BGN4, respectively, for 10 days, followed by DSS supply to induce colitis. The paraprobiotic (HEAT and LYSOZYME) groups had less body weight loss and colon length shortening than the DSS or LIVE groups. The LYSOZYME group exhibited better preserved intestinal barrier integrity than the LIVE group by upregulating gap junction protein expression possibly through activating NOD-like receptor family pyrin domain containing 6/caspase-1/interleukin (IL)-18 signaling. The LYSOZYME group showed downregulated proinflammatory molecules, including p-inhibitor of kappa B proteins alpha (IκBα), cycloxygenase 2 (COX2), IL-1ß, and T-bet, whereas the expression of the regulatory T cell transcription factor, forkhead box P3 expression, was increased. The paraprobiotic groups showed distinct separation of microbiota distribution and improved inflammation-associated dysbiosis. These results suggest that B. bifidum BGN4 paraprobiotics, especially lysozyme-treated BGN4, have a preventive effect against DSS-induced colitis, impacting intestinal barrier integrity, inflammation, and dysbiosis.

The effect of probiotic supplementation on systemic inflammation in dialysis patients.

BACKGROUND: Emerging evidence suggests that intestinal dysbiosis contributes to systemic inflammation and cardiovascular diseases in dialysis patients. The purpose of this study was to evaluate the effects of probiotic supplementation on various inflammatory parameters in hemodialysis (HD) patients. METHODS: Twenty-two patients with maintenance HD were enrolled. These patients were treated twice a day with 2.0 ×1010 colony forming units of a combination of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 3 months. The microbiome and fecal short-chain fatty acids (SCFAs) were analyzed. The percentages of CD14+ CD16+ proinflammatory monocytes and CD4+ CD25+ regulatory T-cells (Tregs) before and after probiotic supplementation were determined by flow cytometry. Serum levels of calprotectin and cytokine responses upon lipopolysaccharide (LPS) challenge were compared before and after probiotic supplementation. RESULTS: Fecal SCFAs increased significantly after probiotic supplementation. Serum levels of calprotectin and interleukin 6 upon LPS stimulation significantly decreased. The anti-inflammatory effects of probiotics were associated with a significant increase in the percentage of CD4+ CD25+ Tregs (3.5% vs. 8.6%, p < 0.05) and also with a decrease of CD14+ CD16+ proinflammatory monocytes (310/ mm2 vs. 194/mm2 , p < 0.05). CONCLUSION: Probiotic supplementation reduced systemic inflammatory responses in HD patients and this effect was associated with an increase in Tregs and a decrease in proinflammatory monocytes. Hence, targeting intestinal dysbiosis might be a novel strategy for decreasing inflammation and cardiovascular risks in HD patients.

Butyl-fructooligosaccharides modulate gut microbiota in healthy mice and ameliorate ulcerative colitis in a DSS-induced model.

Butyl-fructooligosaccharides (B-FOSs) are newly synthesized prebiotics composed of short-chain FOS (GF2, 1-kestose; GF3, nystose; GF4, fructofuranosyl-nystose; GF5, 1-F-(1-b-D-fructofuranosyl)-2-nystose) bound with one or two butyric groups by ester bonds. Previous in vitro studies have shown that B-FOS treatment increases butyrate production and protects the growth of butyrate-producing bacteria during fermentation. The aim of this study was to further test B-FOS as a novel prebiotic compound by evaluating the effect of B-FOS on gut microbiota via 16S rRNA metagenomic analysis in an Institute of Cancer Research (ICR) mouse model and examining its anti-inflammatory efficacy in a mouse model of colitis induced by dextran sodium sulphate (DSS). In the healthy ICR mouse study, linear discriminant analysis effect size results revealed that Bifidobacterium was the representative phylotype in the B-FOS treatment compared to the control group. Furthermore, the cecal butyrate concentration of the B-FOS group was significantly higher than that of the control (P < 0.05). The high concentration of butyrate in the B-FOS treatment was probably associated with the high relative abundance of clusters of orthologous group (COG) 4770 (acetyl/propionyl-CoA carboxylase). In the DSS-induced infection study, B-FOS significantly ameliorated the symptoms of DSS-induced colitis, increased the mRNA expression of occludin, decreased tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL-8) in the colon tissues, and significantly increased cecal butyrate concentrations. These findings suggest that B-FOS ameliorated DSS-induced colitis by maintaining the epithelial barrier and reducing the secretion of inflammation related cytokines.

Lactobacillus acidophilus PIN7 paraprobiotic supplementation ameliorates DSS-induced colitis through anti-inflammatory and immune regulatory effects.

AIMS: This study aimed to evaluate the efficacy of paraprobiotics Lactobacillus acidophilus PIN7 supplementation against dextran sodium sulphate (DSS)-induced colitis in mice and to determine their mechanisms of the action. METHODS AND RESULTS: Ten-week-old female BALB/C mice were randomly divided into five groups. Each group was administered with PBS (control and DSS group), live PIN7 (LIVE group), heat-killed PIN7 (HEAT group) or lysozyme-treated PIN7 (LYSOZYME group) for 10 days followed by 2.5% DSS supply in drinking water for 5 days except for the control group. Colitis-associated DAI scores were significantly (p < 0.05) attenuated in HEAT and LYSOZYME group. The HEAT group exhibited significantly (p < 0.05) lower colonic tissue damage score compared to the DSS group. Furthermore, HEAT and LYSOZYME groups showed significantly (p < 0.05) higher colonic expressions of toll-like receptor (TLR) 6 and intestinal junction protein E-cadherin and occludin compared to the DSS group. LYSOZYME group showed significantly (p < 0.05) lower colonic expressions of Th2 cell-associated pro-inflammatory molecules, namely GATA3 and IL-4, and higher expression of anti-inflammatory NLRP6 and IL-18 compared to the DSS group. Also, HEAT group exhibited significantly (p < 0.05) lower colonic p-IκBα expression compared to the DSS group, while COX-2 expression was significantly (p < 0.05) suppressed by both paraprobiotics supplementation. Paraprobiotics significantly altered the composition of the intestinal microbiota. CONCLUSION: Paraprobiotic L. acidophilus PIN7 ameliorated DSS-induced colitis by regulating immune-modulatory TLR6 signalling and gut microbiota composition. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests paraprobiotic L. acidophilus PIN7 are superior candidates to prevent intestinal inflammation associated with dysregulated immune responses.

Lactobacillus salivarius HHuMin-U Activates Innate Immune Defense against Norovirus Infection through TBK1-IRF3 and NF-κB Signaling Pathways.

The composition of commensal bacteria plays a critical role in controlling immune responses in the intestine. Studies have shown that specific bacterial strains may have the capacity to enhance host immune defense against gastrointestinal viral infections. While norovirus is known to be the most common cause of gastroenteritis, leading to an estimated 200,000 deaths every year, identification of bacterial strains with protective effects against norovirus infection remains elusive. Here, we discovered Lactobacillus salivarius HHuMin-U (HHuMin-U) as a potent antiviral strain against norovirus infection. HHuMin-U significantly suppressed murine norovirus replication and lowered viral RNA titers in macrophages. The transcriptome sequencing (RNA sequencing) analysis revealed that HHuMin-U markedly enhanced the expression level of antiviral interferon-stimulated genes compared to mock treatment. HHuMin-U treatment dose-dependently induced type I interferons (IFN-α and IFN-ß) and tumor necrosis factor-α production in mouse and human macrophages, promoting antiviral innate responses against norovirus infection. Investigation on the molecular mechanism demonstrated that HHuMin-U can activate nuclear factor κB and TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 signaling pathways, leading to the phosphorylation of signal transducer and activator of transcription 1 and signal transducer and activator of transcription 2, the key mediators of interferon-stimulated genes. Finally, oral administration of HHuMin-U increased IFN-ß levels in the ileum of mice and altered the gut microbiome profile. These results suggest the species/strain-specific importance of gut microbial composition for antiviral immune responses and the potential use of HHuMin-U as a probiotic agent.

Probiotics partially attenuate the severity of acute kidney injury through an immunomodulatory effect.

BACKGROUND: A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. METHODS: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. RESULTS: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. CONCLUSION: Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.

Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels.

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.

Lysed and disrupted Bifidobacterium bifidum BGN4 cells promote anti-inflammatory activities in lipopolysaccharide-stimulated RAW 264.7 cells.

Bifidobacterium bifidum BGN4 has been shown to improve the immune system by regulating interleukin (IL)-6 in RAW 264.7 macrophage cells. In this study, the dead cells of B. bifidum BGN4 were produced by enzymatic and physical processing to enhance the inhibition properties of pro-inflammatory cytokines using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Notably, the secretion levels of cytokines such as interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α were decreased by the cell-wall disrupted extracts compared to heat-killed cells. The result suggests that the exposed interior-surface of B. bifidum BGN4 has a potential ability to regulate the immune-responses in the gastrointestinal tract due to major substances in inside-cell wall such as peptidoglycan and teichoic acids. In conclusion, the lysed and disrupted cells from the inside out of B. bifidum BGN4 have anti-inflammatory properties as paraprobiotic agents to control chronic inflammatory related-diseases.

Administration of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI Improves Cognitive and Memory Function in the Mouse Model of Alzheimer's Disease.

Recent evidence indicates that gut microbiota could interact with the central nervous system and affect brain function, including cognition and memory. In this study, we investigated whether Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) alleviated the pathological features in a mouse model of Alzheimer's disease (AD). Administration of B. bifidum BGN4 and B. longum BORI effectively suppressed amyloidosis and apoptotic processes and improved synaptic plasticity by ameliorating the neuroinflammatory response and BDNF expression. Moreover, behavioral tests indicated that B. bifidum BGN4 and B. longum BORI attenuated the cognitive and memory disability of AD mice. Taken together, the present study highlights the therapeutic potential of B. bifidum BGN4 and B. longum BORI for suppressing the pathological features of AD.