Probiotics induce intestinal IgA secretion in weanling mice potentially through promoting intestinal APRIL expression and modulating the gut microbiota composition.

Intestinal infections are strongly associated with infant mortality, and intestinal immunoglobulin A (IgA) is important to protect infants from intestinal infections after weaning. This study aims to screen probiotics that can promote the production of intestinal IgA after weaning and further explore their potential mechanisms of action. In this study, probiotics promoting intestinal IgA production were screened in weanling mouse models. The results showed that oral administration of Bifidobacterium bifidum (B. bifidum) FL228.1 and Bifidobacterium bifidum (B. bifidum) FL276.1 significantly enhanced IgA levels in the small intestine and upregulated the expression of a proliferation-inducing ligand (APRIL) and its upstream regulatory factor toll-like receptor 4 (TLR4). Furthermore, B. bifidum FL228.1 upregulated the relative abundance of Lactobacillus, while B. bifidum FL276.1 increased the relative abundance of Marvinbryantia and decreased Mucispirillum, further elevating intestinal IgA levels. In summary, B. bifidum FL228.1 and B. bifidum FL276.1 can induce IgA production in the intestinal tract of weanling mice by promoting intestinal APRIL expression and mediating changes in the gut microbiota, thus playing a significant role in enhancing local intestinal immunity in infants.

Effect of Fermented Milk Supplemented with Nisin or Plantaricin Q7 on Inflammatory Factors and Gut Microbiota in Mice.

Lactic-acid-bacteria-derived bacteriocins are used as food biological preservatives widely. Little information is available on the impact of bacteriocin intake with food on gut microbiota in vivo. In this study, the effects of fermented milk supplemented with nisin (FM-nisin) or plantaricin Q7 (FM-Q7) from Lactiplantibacillus plantarum Q7 on inflammatory factors and the gut microbiota of mice were investigated. The results showed that FM-nisin or FM-Q7 up-regulated IFN-γ and down-regulated IL-17 and IL-12 in serum significantly. FM-nisin down-regulated TNF-α and IL-10 while FM-Q7 up-regulated them. The results of 16S rRNA gene sequence analysis suggested that the gut microbiome in mice was changed by FM-nisin or FM-Q7. The Firmicutes/Bacteroides ratio was reduced significantly in both groups. It was observed that the volume of Akkermansia_Muciniphila was significantly reduced whereas those of Lachnospiraceae and Ruminococcaceae were increased. The total number of short-chain fatty acids (SCFAs) in the mouse feces of the FM-nisin group and FM-Q7 group was increased. The content of acetic acid was increased while the butyric acid content was decreased significantly. These findings indicated that FM-nisin or FM-Q7 could stimulate the inflammation response and alter gut microbiota and metabolic components in mice. Further in-depth study is needed to determine the impact of FM-nisin or FM-Q7 on the host's health.

Correction: Lactobacillus fermentum F40-4 ameliorates hyperuricemia by modulating the gut microbiota and alleviating inflammation in mice.

Correction for 'Lactobacillus fermentum F40-4 ameliorates hyperuricemia by modulating the gut microbiota and alleviating inflammation in mice' by Jiayuan Cao et al., Food Funct., 2023, 14, 3259-3268, https://doi.org/10.1039/D2FO03701G.

Oral Milk-Derived Extracellular Vesicles Inhibit Osteoclastogenesis and Ameliorate Bone Loss in Ovariectomized Mice by Improving Gut Microbiota.

Milk-derived extracellular vesicles can improve intestinal health and have antiosteoporosis potential. In this paper, we explored the effects of bovine raw milk-derived extracellular vesicles (mEVs) on ovariectomized (OVX) osteoporotic mice from the perspective of the gut-bone axis. mEVs could inhibit osteoclast differentiation and improve microarchitecture. The level of osteoporotic biomarkers in OVX mice was restored after the mEVs intervened. Compared with OVX mice, mEVs could enhance intestinal permeability, reduce endotoxin levels, and improve the expression of TNF-α, IL-17, and IL-10. 16S rDNA sequencing indicated that mEVs altered the composition of gut microbiota, specifically for Bacteroides associated with short-chain fatty acids (SCFAs). In-depth analysis of SCFAs demonstrated that mEVs could restore acetic acid, propionic acid, valeric acid, and isovaleric acid levels in OVX mice. Correlation analysis revealed that changed gut microbiota and SCFAs were significantly associated with gut inflammation and osteoporotic biomarkers. This study demonstrated that mEVs could inhibit osteoclast differentiation and improve osteoporosis by reshaping the gut microbiota, increasing SCFAs, and decreasing the level of pro-inflammatory cytokines and osteoclast differentiation-related factors in OVX mice. These findings provide evidence for the use of mEVs as a food supplement for osteoporosis.

Bifidobacterium improves oestrogen-deficiency-induced osteoporosis in mice by modulating intestinal immunity.

Osteoporosis has become one of the major diseases that threaten the health of middle-aged and elderly people, and with the growth of an ageing population, more and more people are affected by osteoporosis these days. In recent years, intestinal flora has been found to affect the host immune system, and an overactive immune system is closely related to bone resorption. Probiotics can effectively improve bone density and strength, reduce bone loss, and improve osteoporosis, but their mechanism of action and relationship with intestinal microbiota are still unclear. In this study, two strains of Bifidobacterium (Bifidobacterium bifidum FL228.1 and Bifidobacterium animalis subsp. Lactis F1-7) that can alleviate intestinal inflammation were screened based on previous experiments. Through the construction of an ovariectomized mouse model, the improvement of osteoporosis by Bifidobacterium was detected, and the influence of Bifidobacterium on intestinal immunity was explored. The results show that Bifidobacterium treatment significantly improved bone mineral density (BMD), bone volume/total volume ratio (BV/TV), and trabecular number (Tb·N), and effectively suppressed bone loss. Furthermore, Bifidobacterium treatment could inhibit the expression of inflammatory cytokines in the gut, alleviate gut inflammation, and thus suppress excessive osteoclast generation. Its mechanism of action includes factors that protect the mucosal barrier, including occludin, ZO-1, claudin-2, and MUC2, and the reduction of pro-inflammatory M1 macrophages. B. bifidum FL228.1 increased the abundance of beneficial bacteria in the colon, including Lactobacillus and Colidextribacter. B. animalis F1-7 increased the abundance of Bifidobacterium and decreased the abundance of Desulfovibrio and Ruminococcus in the colon. These research findings expand our understanding of the gut-bone axis and provide new guidance for the development of probiotic-based therapies for osteoporosis in the future.

Preparation and synbiotic interaction mechanism of microcapsules of Bifidobacterium animalis F1-7 and human milk oligosaccharides (HMO).

Probiotics such as Bifidobacterium spp. generally possess important physiological functions. However, maintaining probiotic viability is a challenge during processing, storage, and digestive transit period. Microencapsulation is widely considered to be an attractive approach. In this study, B. animalis F1-7 microcapsules and B. animalis F1-7-HMO microcapsules were successfully prepared by emulsification/internal gelation with high encapsulation efficiency (90.67 % and 92.16 %, respectively). The current study revealed that HMO-supplemented microcapsules exhibited more stable lyophilized forms and thermal stability. Additionally, a significant improvement in probiotic cell viability was observed in such microcapsules during simulated gastrointestinal (GI) fluids or storage. We also showed that the individual HMO mixtures 6'-SL remarkably promoted the growth and acetate yield of B. animalis F1-7 for 48 h (p < 0.05). The synbiotic combination of 6'-SL with B. animalis F1-7 enhanced SCFAs production in vitro fecal fermentation, decreasing several harmful intestinal bacteria such as Dorea, Escherichia-Shigella, and Streptococcus while enriching the probiotic A. muciniphila. This study provides strong support for HMO or 6'-SL combined with B. animalis F1-7 as an innovative dietary ingredient to bring health benefits. The potential of the synbiotic microcapsules with this combination merits further exploration for future use in the food industry.

Up-regulation of sortase-dependent pili in Bifidobacterium longum BBMN68 in response to bile stress enhances its adhesion to HT-29 cells.

Adhesion to gastrointestinal tract is crucial for bifidobacteria to exert their probiotic effects. Our previous work found that bile salts significantly enhance the adhesion ability of Bifidobacterium longum BBMN68 to HT-29 cells. In this study, trypsin-shaving and LC-MS/MS-based surface proteomics were employed to identify surface proteins involved in bile stress response. Among the 829 differentially expressed proteins, 56 up-regulated proteins with a fold change >1.5 were subjected to further analysis. Notably, the minor pilin subunit FimB was 4.98-fold up-regulated in response to bile stress. In silico analysis and RT-PCR confirmed that gene fimB, fimA and srtC were co-transcribed and contributed to the biosynthesis of sortase-dependent pili Pil1. Moreover, scanning electron microscopy and immunogold electron microscopy assays showed increased abundance and length of Pil1 on BBMN68 under bile stress. As the major pilin subunit FimA serves as adhesion component of Pil1, an inhibition assay using anti-FimA antibodies further confirmed the critical role of Pil1 in mediating the adhesion of BBMN68 to HT-29 cells under bile stress. Our findings suggest that the up-regulation of Pil1 in response to bile stress enhances the adhesion of BBMN68 to intestinal epithelial cells, highlighting a novel mechanism of gut persistence in B. longum strains.

Metabolites 13,14-Dihydro-15-keto-PGE2 Participates in Bifidobacterium animalis F1-7 to Alleviate Opioid-Induced Constipation by 5-HT Pathway.

SCOPE: People suffer from constipation caused by many factors, including constipation (Opioid-Induced Constipation, OIC) during analgesic treatment. Microorganisms may be a potent solution to this problem, but the mechanism is still unclear. METHODS AND RESULTS: Based on models in vivo and in vitro, the potential mechanism involving Bifidobacterium animalis F1-7 (B. animalis F1-7), screened in the previous studies, is explored through non-targeted metabonomics, electrophysiological experiment and molecular level docking. The results showed that B. animalis F1-7 effectively alleviates OIC and promotes the expression of chromogranin A (CGA) and 5-hydroxytryptamine (5-HT). The metabolite 13,14-dihydro-15-keto-PGE2 related to B. animalis F1-7 is found, which has a potential improvement effect on OIC at 20 mg kg BW-1 in vivo. At 30 ng mL-1 it effectively stimulates secretion of CGA/5-HT (408.95 ± 1.18 ng mL-1 ) by PC-12 cells and changes the membrane potential potassium ion current without affecting the sodium ion current in vitro. It upregulates the target of free fatty acid receptor-4 protein(FFAR4/ß-actin, 0.81 ± 0.02). CONCLUSION: The results demonstrate that metabolite 13,14-dihydro-15-keto-PGE2 participated in B. animalis F1-7 to alleviate OIC via the 5-HT pathway.

Effect of Extracelluar Vesicles Derived from Akkermansia muciniphila on Intestinal Barrier in Colitis Mice.

Inflammatory bowel disease (IBD) is a chronic and recurrent disease. It has been observed that the incidence and prevalence of IBD are increasing, which consequently raises the risk of developing colon cancer. Recently, the regulation of the intestinal barrier by probiotics has become an effective treatment for colitis. Akkermansia muciniphila-derived extracellular vesicles (Akk EVs) are nano-vesicles that contain multiple bioactive macromolecules with the potential to modulate the intestinal barrier. In this study, we used ultrafiltration in conjunction with high-speed centrifugation to extract Akk EVs. A lipopolysaccharide (LPS)-induced RAW264.7 cell model was established to assess the anti-inflammatory effects of Akk EVs. It was found that Akk EVs were able to be absorbed by RAW264.7 cells and significantly reduce the expression of nitric oxide (NO), TNF-α, and IL-1ß (p < 0.05). We explored the preventative effects on colitis and the regulating effects on the intestinal barrier using a mouse colitis model caused by dextran sulfate sodium (DSS). The findings demonstrated that Akk EVs effectively prevented colitis symptoms and reduced colonic tissue injury. Additionally, Akk EVs significantly enhanced the effectiveness of the intestinal barrier by elevating the expression of MUC2 (0.53 ± 0.07), improving mucus integrity, and reducing intestinal permeability (p < 0.05). Moreover, Akk EVs increased the proportion of the beneficial bacteria Firmicutes (33.01 ± 0.09%) and downregulated the proportion of the harmful bacteria Proteobacteria (0.32 ± 0.27%). These findings suggest that Akk EVs possess the ability to regulate immune responses, protect intestinal barriers, and modulate the gut microbiota. The research presents a potential intervention approach for Akk EVs to prevent colitis.

Bacteriocin-Producing Lactiplantibacillus plantarum YRL45 Enhances Intestinal Immunity and Regulates Gut Microbiota in Mice.

Bacteriocins production is one of important beneficial characteristics of probiotics, which has antibacterial property against intestinal pathogens and is helpful for regulating intestinal flora. To investigate the impact of bacteriocin-producing probiotics on gut microecology, bacteriocin-producing Lactiplantibacillus plantarum YRL45 was orally administered to mice. The results revealed that it promoted the release of cytokines and improved the phagocytic activity of peritoneal macrophages to activate the immune regulation system. L. plantarum YRL45 was conducive to maintaining the morphology of colon tissue without inflammation and increasing the ratio of villus height to crypt depth in the ileum. The gene expression levels of Muc2, ZO-1 and JAM-1 were significantly up-regulated in the ileum and colon, and the gene expression of Cramp presented an upward trend with L. plantarum YRL45 intervention. Moreover, L. plantarum YRL45 remarkably enhanced the levels of immunoglobulins sIgA, IgA and IgG in the intestine of mice. The 16S rRNA gene analysis suggested that L. plantarum YRL45 administration up-regulated the relative abundance of the beneficial bacteria Muribaculaceae and Akkermansia, down-regulated the abundance of the pathogenic bacteria Lachnoclostridium, and promoted the production of acetic acid, propionic acid and total short-chain fatty acids (SCFAs) in mice feces. Our findings indicated that L. plantarum YRL45 had the potential to be developed as a novel probiotic to regulate the intestinal barrier by altering gut microbiota to enhance intestinal immunity and ameliorate intestinal flora balance.

Protective Effects of Bacteriocin-Producing Lactiplantibacillus plantarum on Intestinal Barrier of Mice.

Bacteriocins are crucial metabolites of probiotics that display beneficial functions. The intestinal barrier is an important target on which probiotics exert their intestinal health activity. However, the impacts of bacteriocin-producing probiotics on the intestinal barrier are unclear. In this study, the effects of bacteriocin-producing Lactiplantibacillus plantarum Q7 and L. plantarum F3-2 on the intestinal barrier of mice were explored. It was shown that L. plantarum Q7 promoted the expression of mucin MUC2 to enhance the protection provided by the intestinal mucus layer. L. plantarum Q7 up-regulated the gene expression of intestinal tight junction proteins ZO-1 and JAM-1 significantly, and L. plantarum F3-2 up-regulated ZO-1 and Claudin-1 markedly, which exhibited tight junction intestinal barrier function. The two strains promoted the release of IgA and IgG at varying degrees. The antimicrobial peptide gene RegIIIγ was up-regulated markedly, and the gene expression of inflammatory cytokines appeared to exhibit an upward trend with L. plantarum Q7 treatment, so as to enhance intestinal immune regulation function. Furthermore, L. plantarum Q7 and L. plantarum F3-2 increased the abundance of the beneficial bacteria Muribaculaceae, inhibited the growth of the harmful bacteria Parabacteroides, and facilitated the synthesis of total short-chain fatty acids (SCFAs), which seemed to favor the prevention of metabolic diseases. Our results suggested that L. plantarum Q7 and L. plantarum F3-2 showed strain specificity in their protective effects on the intestinal chemical, physical, immunological and biological barriers of mice, which provided theoretical support for the selective utilization of bacteriocin-producing strains to regulate host health.

Lactobacillus paracasei subsp. paracasei X12 Strain Induces Apoptosis in HT-29 Cells through Activation of the Mitochondrial Pathway.

L. paracasei subsp. paracasei X12 was obtained from traditional cheese produced in northwestern China. In this study, we showed that whole peptidoglycan (WPG), extracted from L. paracasei subsp. paracasei X12, inhibited proliferation and induced apoptosis in HT-29 cells in a dose-dependent manner. In addition, WPG-induced apoptosis was associated with the loss of mitochondrial membrane potential (Ψm), the release of cytochrome c (Cyto-C) from mitochondrialto cytosolic spaces, activation of Caspase 3, and accumulation of intracellular reactive oxygen species (ROS). Finally, semi-quantitative RT-PCR showed that these events were accompanied by upregulation of proapoptotic genes (Bax or Bad) and downregulation of antiapoptotic genes (Bcl-xl). Taken together, our results demonstrated that WPG induced apoptosis in HT-29 cells through activation of the mitochondrial pathway. WPG exerted only minor toxicity upon noncancerous cells and therefore might be used as a natural agent in the treatment of cancer in future.

Lipidomics insight on differences between human MFGM and dietary-derived lipids.

Milk fat globule membrane (MFGM) contains lipids, which are essential for promoting infant brain development and improving cognition. In this study, the lipid differences between human MFGM and four dietary lipid sources (cow MFGM, soybean, krill, and yolk) were compared using the UHPLC-Q-Exactive MS-based lipidomics techniques. A total of 45 lipid classes and 5048 lipid species were detected. The analysis of phospholipid classes revealed that the lipid composition of human MFGM and cow MFGM was more similar than the other dietary-derived lipids. Additionally, the human MFGM lipid species were compared with cow MFGM, soybean, krill, and yolk, and 401, 416, 494, and 444 significantly different lipids were identified, respectively. Through lipid metabolic pathway analysis, differential lipids were mainly involved in the glycerophospholipid metabolic pathway. Overall, these results will provide a rationale for the future addition of lipids to infant formula to more closely approximate human MFGM lipid profiles.

Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis.

Milk-derived extracellular vesicles (mEVs) have been proposed as a potential nanomedicine for intestinal disorders; however, their impact on intestinal barrier integrity in gut inflammation and associated metabolic diseases has not been explored yet. Here, mEVs derived from bovine and human breast milk exert similar protective effects on epithelial tight junction functionality in vitro, survive harsh gastrointestinal conditions ex vivo, and reach the colon in vivo. Oral administration of mEVs restores gut barrier integrity at multiple levels, including mucus, epithelial, and immune barriers, and prevents endotoxin translocation into the liver in chemical-induced experimental colitis and diet-induced nonalcoholic steatohepatitis (NASH), thereby alleviating gut disorders, their associated liver inflammation, and NASH. Oral administration of mEVs has potential in the treatment of gut inflammation and gut-liver axis-associated metabolic diseases via protection of intestinal barrier integrity.

Lactobacillus fermentum F40-4 ameliorates hyperuricemia by modulating the gut microbiota and alleviating inflammation in mice.

Hyperuricemia (HUA) is a systemic disease characterized by a disorder of purine metabolism and an abnormal increase in the serum level of uric acid (UA). Probiotics can exert potential therapeutic benefits against some metabolic diseases by regulating the intestinal microbiota. Lactobacillus fermentum F40-4 with UA-lowering activity of 87.40% was screened using purine as the target in vitro. The UA-lowering activity of L. fermentum F40-4 was further explored in a mouse model of HUA in vivo. L. fermentum F40-4 could downregulate serum levels of UA, blood urea nitrogen, creatinine, and xanthine oxidase by 40.84%, 11.61%, 57.66%, and 41.79%, respectively. L. fermentum F40-4 restored organ damage, and adjusted enzyme activity and transporter expression to promote the metabolic level of UA. In addition, L. fermentum F40-4 could reshape the gut microbiota and suppress inflammation to ameliorate HUA. An increment in intestinal UA excretion was documented. These findings suggest that L. fermentum F40-4 might serve as a potential probiotic for the prevention and treatment of HUA.

Molecular Organization and Functional Analysis of a Novel Plasmid-Borne cps Gene Cluster from Lactiplantibacillus plantarum YC41.

Capsular polysaccharide (CPS) can tightly attach to bacterial surfaces and plays a critical role in protecting microorganisms from environmental stresses. However, the molecular and functional properties of some plasmid-borne cps gene clusters are poorly understood. In this study, comparative genomics of the draft genomes of 21 Lactiplantibacillus plantarum strains revealed that the specific gene cluster for CPS biosynthesis was observed only in the 8 strains with a ropy phenotype. Furthermore, the complete genomes showed that the specific gene cluster cpsYC41 was located on the novel plasmid pYC41 in L. plantarum YC41. In silico analysis confirmed that the cpsYC41 gene cluster contained the dTDP-rhamnose precursor biosynthesis operon, the repeating-unit biosynthesis operon, and the wzx gene. The insertional inactivation of the rmlA and cpsC genes abolished the ropy phenotype and reduced the CPS yields by 93.79% and 96.62%, respectively, in L. plantarum YC41 mutants. These results revealed that the cpsYC41 gene cluster was responsible for CPS biosynthesis. Moreover, the survival rates of the YC41-rmlA- and YC41-cpsC- mutants under acid, NaCl, and H2O2 stresses were decreased by 56.47 to 93.67% compared to that of the control strain. Furthermore, the specific cps gene cluster was also confirmed to play a vital role in CPS biosynthesis in L. plantarum MC2, PG1, and YD2. These findings enhance our understanding of the genetic organization and gene functions of plasmid-borne cps gene clusters in L. plantarum. IMPORTANCE Capsular polysaccharide is well known to protect bacteria against various environmental stresses. The gene cluster for CPS biosynthesis is typically organized in the chromosome in bacteria. It is worth noting that complete genome sequencing showed that a novel plasmid pYC41-borne cpsYC41 gene cluster was identified in L. plantarum YC41. The cpsYC41 gene cluster included the dTDP-rhamnose precursor biosynthesis operon, the repeating-unit biosynthesis operon, and the wzx gene, which was verified by the significantly decreased CPS yield and the absent ropy phenotype in the corresponding mutants. The cpsYC41 gene cluster plays an important role in bacterial survival under environmental stress, and the mutants had decreased fitness under stress conditions. The vital role of this specific cps gene cluster in CPS biosynthesis was also confirmed in other CPS-producing L. plantarum strains. These results advanced a better understanding of the molecular mechanisms of plasmid-borne cps gene clusters and the protective functionality of CPS.

Metagenomic insights into bacterial communities and functional genes associated with texture characteristics of Kazakh artisanal fermented milk Ayran in Xinjiang, China.

The complex microflora of traditional fermented milk is crucial to milk coagulation mainly through acid and protease production; however, it is still unclear which microbes and proteases significantly influence the texture of Ayran, a Kazakh artisanal fermented milk in Xinjiang, China. In this study, fifty-nine samples of Ayran were collected and investigated on texture properties. Finally, six Ayran samples with different texture features were screened out, and the taxonomic and functional attributes of their microbiota were characterized by metagenomics. The results showed that the hardness of the fermented milk in Yili Kazakh Autonomous Prefecture was significantly higher than that in other pasture areas. Lactobacillus and Lactococcus were the core genera that affected the coagulation quality of milk. Furthermore, we found that the proline iminopeptidase pip (EC 3.4.11.5) gene of Lactobacillus helveticus and Limosilactobacillus fermentum and the dipeptidase E pepE (EC 3.4.13.21) gene of Lactococcus lactis were most associated with the coagulation quality of fermented milk. Furthermore, positive correlations were observed among the hardness of fermented milk, the activity of the proteases, and the corresponding functional gene expressions.

Probiotics Alleviate Food Protein Allergy in Mice by Activating TLR4 Signaling Pathway.

SCOPE: Food allergy has become a world recognized public health problem due to its versatility and lack of efficacious methods for its treatment. Probiotics supplement is a potential way to prevent food allergy. METHODS AND RESULTS: In this study, potential strains are screen out by peripheral blood mononuclear cells (PBMCs), and their abilities of alleviating food allergy are examined using a mouse model induced by ovalbumin (OVA). The results show that six strains increase ratio of interferon-γ (IFN-γ)/interleukin (IL)-4 secreted by PBMCs with good abilities in intestinal adhesion and gastrointestinal tolerance. Oral administration of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) attenuates allergic responses in allergy mice, including allergic symptoms, mast cells aggregation and activity, serum OVA-special-immunoglobulins E (OVA-sIgE) production. KV9 and FN3 upregulate the production of IFN-γ/IL-4 in splenocytes, increase the genes and proteins expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (Myd88) and interferon regulatory factor (IRF)-1 in allergic mice spleen, and decrease the IRF-4. CONCLUSION: The study demonstrates that KV9 and FN3 possess anti-allergic activities via activation of TLR4 pathway and modulating the expression of IRF-1 and IRF-4 which leads to T helper type 1 (Th1)/T helper type 2 (Th2) cell immunology balance.

Oral Administration of Bovine Milk-Derived Extracellular Vesicles Attenuates Cartilage Degeneration via Modulating Gut Microbiota in DMM-Induced Mice.

Osteoarthritis (OA) is the most common joint disease primarily characterized by cartilage degeneration. Milk-derived extracellular vesicles (mEVs) were reported to inhibit catabolic and inflammatory processes in the cartilage of OA patients. However, the current therapies target the advanced symptoms of OA, and it is significant to develop a novel strategy to inhibit the processes driving OA pathology. In this study, we investigated the therapeutic potential of mEVs in alleviating OA in vivo. The results revealed that mEVs ameliorated cartilage degeneration by increasing hyaline cartilage thickness, decreasing histological Osteoarthritis Research Society International (OARSI) scores, enhancing matrix synthesis, and reducing the expression of cartilage destructive enzymes in the destabilization of medial meniscus (DMM) mice. In addition, the disturbed gut microbiota in DMM mice was partially improved upon treatment with mEVs. It was observed that the pro-inflammatory bacteria (Proteobacteria) were reduced and the potential beneficial bacteria (Firmicutes, Ruminococcaceae, Akkermansiaceae) were increased. mEVs could alleviate the progression of OA by restoring matrix homeostasis and reshaping the gut microbiota. These findings suggested that mEVs might be a potential therapeutic dietary supplement for the treatment of OA.

Bifidobacterium bifidum Ameliorates DSS-Induced Colitis in Mice by Regulating AHR/NRF2/NLRP3 Inflammasome Pathways through Indole-3-lactic Acid Production.

In this study, the effectors and mechanisms of Bifidobacterium bifidum FL-276.1 and B. bifidum FL-228.1 in alleviating dextran sulfate sodium (DSS)-induced colitis were investigated. Both FL-276.1 and FL-228.1 significantly alleviated DSS-induced colitis, whether they were supplemented from the beginning of the experiment (whole course intervention) or after the DSS induction started (partial intervention). Aryl hydrocarbon receptor (AHR) and the nuclear factor erythroid 2-related factor 2 (NRF2) pathways were activated in mice colons, while the NLR family pyrin domain containing 3 (NLRP3) was downregulated under the whole course intervention modes. Indole-3-lactic acid, an AHR ligand produced by FL-276.1 and FL-228.1, could regulate the AHR/NRF2/NLRP3 pathway in Caco-2 monolayers, thus upregulating the tight junction proteins and protecting the integrity of the epithelial barrier. These results are conducive to promoting clinical trials and product development of probiotics for alleviating colitis.