Chondroitin sulfate-based universal nanoparticle delivers angiogenic inhibitor and paclitaxel to exhibit a combination of chemotherapy and anti-angiogenic therapy.

Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors.

Diversity Analysis of Intestinal Bifidobacteria in the Hohhot Population.

(1) Background: Bifidobacterium plays a pivotal role within the gut microbiota, significantly affecting host health through its abundance and composition in the intestine. Factors such as age, gender, and living environment exert considerable influence on the gut microbiota, yet scant attention has been directed towards understanding the specific effects of these factors on the Bifidobacterium population. Therefore, this study focused on 98 adult fecal samples to conduct absolute and relative quantitative analyses of bifidobacteria. (2) Methods: Using droplet digital PCR and the PacBio Sequel II sequencing platform, this study sought to determine the influence of various factors, including living environment, age, and BMI, on the absolute content and biodiversity of intestinal bifidobacteria. (3) Results: Quantitative results indicated that the bifidobacteria content in the intestinal tract ranged from 106 to 109 CFU/g. Notably, the number of bifidobacteria in the intestinal tract of the school population surpassed that of the off-campus population significantly (p = 0.003). Additionally, the group of young people exhibited a significantly higher count of bifidobacteria than the middle-aged and elderly groups (p = 0.041). The normal-weight group displayed a significantly higher bifidobacteria count than the obese group (p = 0.027). Further analysis of the relative abundance of bifidobacteria under different influencing factors revealed that the living environment emerged as the primary factor affecting the intestinal bifidobacteria structure (p = 0.046, R2 = 2.411). Moreover, the diversity of bifidobacteria in the intestinal tract of college students surpassed that in the out-of-school population (p = 0.034). This was characterized by a notable increase in 11 strains, including B. longum, B. bifidum, and B. pseudolongum, in the intestinal tract of college students, forming a more intricate intestinal bifidobacteria interaction network. (4) Conclusions: In summary, this study elucidated the principal factors affecting intestinal bifidobacteria and delineated their characteristics of intestinal bifidobacteria in diverse populations. By enriching the theory surrounding gut microbiota and health, this study provides essential data support for further investigations into the intricate dynamics of the gut microbiota.

Therapeutic Effect of Proteinase-Activated Receptor-1 Antagonist on Colitis-Associated Carcinogenesis.

BACKGROUND & AIMS: Inflammatory bowel disease is associated with carcinogenesis, which limits the prognosis of the patients. The local expression of proteinases and proteinase-activated receptor 1 (PAR1) increases in inflammatory bowel disease. The present study investigated the therapeutic effects of PAR1 antagonism on colitis-associated carcinogenesis. METHODS: A colitis-associated carcinogenesis model was prepared in mice by treatment with azoxymethane (AOM) and dextran sulfate sodium (DSS). PAR1 antagonist E5555 was administered in long- and short-term protocol, starting on the day of AOM injection and 1 week after completing AOM/DSS treatment, respectively. The fecal samples were collected for metagenome analysis of gut microbiota. The intestinal myofibroblasts of the Crohn's disease patients were used to elucidate underlying cellular mechanisms. Caco-2 cells were used to investigate a possible source of PAR1 agonist proteinases. RESULTS: AOM/DSS model showed weight loss, diarrhea, tumor development, inflammation, fibrosis, and increased production of inflammatory cytokines. The ß-diversity, but not α-diversity, of microbiota significantly differed between AOM/DSS and control mice. E5555 alleviated these pathological changes and altered the microbiota ß-diversity in AOM/DSS mice. The thrombin expression was up-regulated in tumor and non-tumor areas, whereas PAR1 mRNA expression was higher in tumor areas compared with non-tumor areas. E5555 inhibited thrombin-triggered elevation of cytosolic Ca2+ concentration and ERK1/2 phosphorylation, as well as IL6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in intestinal myofibroblasts. Caco-2 cell-conditioned medium contained immunoreactive thrombin, which cleaved the recombinant protein containing the extracellular domain of PAR1 at the thrombin cleavage site. CONCLUSIONS: PAR1 antagonism is proposed to be a novel therapeutic strategy for treatment of inflammatory bowel disease and its associated carcinogenesis.

Long-Term Tracking of the Effects of Colostrum-Derived Lacticaseibacillus rhamnosus Probio-M9 on Gut Microbiota in Mice with Colitis-Associated Tumorigenesis.

Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the probiotic Probio-M9 on CAC-model mice, tracking the microbiota. Feces were obtained at four time points for evaluation of gut microbiota. The effect of Probio-M9 on tight junction protein expression was evaluated in co-cultured Caco-2 cells. Probio-M9 treatment decreased the number of tumors as well as stool consistency score, spleen weight, inflammatory score, and macrophage expression in the CAC model. Probio-M9 accelerated the recovery of the structure, composition, and function of the intestinal microbiota destroyed by azoxymethane (AOM)/dextran sulfate sodium (DSS) by regulating key bacteria (including Lactobacillus murinus, Muribaculaceae bacterium DSM 103720, Muribaculum intestinale, and Lachnospiraceae bacterium A4) and pathways from immediately after administration until the end of the experiment. Probio-M9 co-culture protected against lipopolysaccharide-induced impairment of tight junctions in Caco-2 cells. This study provides valuable insight into the role of Probio-M9 in correcting gut microbiota defects associated with inflammatory bowel disease carcinogenesis and may have clinical application in the treatment of inflammatory carcinogenesis.

Chondroitin sulfate-modified antiangiogenic peptide conjugate induces cell apoptosis via the mitochondria-mediated pathway to perform antitumor activity.

Tumor growth and metastasis heavily rely on angiogenesis, crucial for solid tumor development. Inhibiting angiogenesis associated with tumors emerges as a potent therapeutic approach. Our previous work synthesized the chondroitin sulfate-modified antiangiogenic peptide CS-ES2-AF (CS-EA), which exhibited better antiangiogenic activity, longer half-life, and more robust targeting. In this work, we further evaluated the stability in vitro, cellular uptake mechanism, cell apoptosis mechanism, antitumor activity in vivo, and safety of CS-EA. The stability of CS-EA was consistently superior to that of EA at different temperatures and in different pH ranges. Furthermore, CS-EA mainly entered EAhy926 cells through the clathrin-mediated endocytosis pathway. CS-EA inhibited endothelial cell proliferation, and induced cell apoptosis through downregulating the Bcl-2, reducing mitochondria membrane potential, upregulating cytochrome c, Caspase 3, and reactive oxygen species levels. CS-EA showed better antitumor activity in the B16 xenografted tumor model, with a tumor inhibition rate 1.92 times higher than EA. Simultaneously, it was observed that CS-EA did not cause any harmful effects on the vital organs of the mice. These findings indicate that CS-EA holds significant promise for the treatment of tumors.

Isolation, purification, and antiosteoporosis activity of donkey bone collagen from discarded bone and its antioxidant peptides.

Oxidative stress plays a crucial role in the development of osteoporosis. In this study, it was observed that donkey bone collagen (DC) at a concentration of 500 µg/mL scavenged 17.89 % of 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals, indicating its antioxidant properties. Additionally, when an oxidative damage osteoblast model was created using H2O2, 100 µg/mL DC demonstrated the ability to enhance cell survival by 27.31 %. Furthermore, 50 µg/mL DC increased the intracellular differentiation marker alkaline phosphatase (ALP) level by 62.65 %. Additionally, the study revealed that DC significantly increased the expression of osteoporosis-related factors in serum and effectively restored the abnormal structure of spongy bone in mice osteoporosis model. Peptides (GGWFL, ANLGPA, and GWFK) isolated from DC through gastrointestinal digestion and subsequent enzymatic purification in vitro demonstrated the ability to safeguard osteoblasts from H2O2-induced damage by reducing intracellular reactive oxygen species (ROS). This protection resulted in enhanced cell survival and promoted osteoblast differentiation. This investigation underscores that DC can shield oxidative damage osteoblast model from oxidative stress, ameliorate osteoporosis, and enhance bone density in mice osteoporosis model. These findings suggest various DC applications in the food and medicine industries.

Dietary supplementation with Lactiplantibacillus plantarum P-8 improves the growth performance and gut microbiota of weaned piglets.

Weaning is a stressful event in the pig life cycle. We hypothesized that probiotics could be potential alternatives to antibiotics for promoting growth and ameliorating stress in weaning piglets via gut microbiota modulation and, thus, investigated the beneficial effects of dietary probiotic supplementation in weaning pigs. Ninety weaning piglets (Landrace × large white, 45 males and 45 females, 25 days of age) were randomized into three dietary treatments (30 piglets/treatment, divided into five replicates/treatment, i.e., six piglets/replicate) in this 28-day trial: control (C group, basal diet); probiotic [lactic acid bacteria (LAB) group, basal diet plus Lactiplantibacillus plantarum P-8]; and antibiotic (A group; basal diet plus chlortetracycline). The piglets' growth performance [average daily gain, average daily feed intake (ADFI), and feed conversion ratio (FCR)], immune and antioxidant markers, ileal mucosal morphology, and ileal and colonic microbiomes were compared among treatment groups. Compared to the C and A groups, probiotic supplementation significantly decreased the ADFI, FCR, and ileal mucosal crypt depth while increasing the villus height-to-crypt depth ratio, hepatic glutathione peroxidase and catalase activities, and serum levels of interleukin-2. Both probiotic and antibiotic treatments modulated the piglets' gut microbiomes, with more L. plantarum in the LAB group and more Eubacterium rectale and Limosilactobacillus reuteri in the A group. Probiotic supplementation significantly increased the relative abundance of genes encoding the acetylene, galactose, and stachyose degradation pathways, potentially enhancing nutrient absorption, energy acquisition, and growth performance. Probiotics are effective alternatives to antibiotics for promoting the health of piglets, possibly via gut microbiome modulation.IMPORTANCEWeaning impacts piglet health, performance, and mortality. Antibiotic treatment during weaning can mitigate the negative effects on growth. However, antibiotic use in livestock production contributes to the emergence of antibiotic resistance, which is a threat to global public health. This comprehensive study describes the gut microbial composition and growth performance of weaned piglets after dietary supplementation with Lactiplantibacillus plantarum P-8 or antibiotics. L. plantarum P-8 ameliorated stress and improved antioxidant capacity and growth performance in weaned piglets, accompanied by gut microbiota improvement. L. plantarum P-8 is an effective substitute for antibiotics to promote the health of weaned piglets while avoiding the global concern of drug resistance.

Aberrantly High FBXO31 Impairs Oocyte Quality in Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI), which is defined as loss of ovarian function that occurs before the age of 40, causes menstrual disturbances, infertility, and diverse health problems in females. Despite the limited understanding of the molecular basis underlying POI pathology, we had previously demonstrated that the cooperation of miR-106a and FBXO31 plays a pivotal role in diminished ovarian reserve (DOR), with FBXO31 serving as a putative target of miR-106a. In this study, we found that FBXO31 is aberrantly expressed in granulosa cells of POI patients, leading to accumulated reactive oxygen species (ROS) and cell apoptosis via the p53/ROS pathway. Furthermore, our results demonstrated that high levels of FBXO31 in mouse ovaries impair oocyte quality. Our study revealed that FBXO31 may serve as a novel indicator and play a significant role in the etiology of POI.

Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics.

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity. Tumour delivery and treatment outcomes are superior in old versus young mice, probably due to an age-related decline in the ability of hepatic phagocytes to take up and remove nanoparticles. Transcriptomic- and protein-level analysis at the single-cell and bulk levels reveals an age-associated decrease in the numbers of hepatic macrophages that express the scavenger receptor MARCO in mice, non-human primates and humans. Therapeutic blockade of MARCO is shown to decrease the phagocytic uptake of nanoparticles and improve the antitumour effect of clinically approved cancer nanotherapeutics in young but not aged mice. Together, these results reveal an age-associated disparity in the phagocytic clearance of nanotherapeutics that affects their antitumour response, thus providing a strong rationale for an age-appropriate approach to cancer nanomedicine.

Semidiscrete optical vortex droplets in quasi-phase-matched photonic crystals.

What we believe is a new scheme for producing semidiscrete self-trapped vortices ("swirling photon droplets") in photonic crystals with competing quadratic (χ(2)) and self-defocusing cubic (χ(3)) nonlinearities is proposed. The photonic crystal is designed with a striped structure, in the form of spatially periodic modulation of the χ(2) susceptibility, which is imposed by the quasi-phase-matching technique. Unlike previous realizations of semidiscrete optical modes in composite media, built as combinations of continuous and arrayed discrete waveguides, the semidiscrete vortex "droplets" are produced here in the fully continuous medium. This work reveals that the system supports two types of semidiscrete vortex droplets, viz., onsite- and intersite-centered ones, which feature, respectively, odd and even numbers of stripes, N. Stability areas for the states with different values of N are identified in the system's parameter space. Some stability areas overlap with each other, giving rise to the multistability of states with different N. The coexisting states are mutually degenerate, featuring equal values of the Hamiltonian and propagation constant. An experimental scheme to realize the droplets is outlined, suggesting new possibilities for the long-distance transmission of nontrivial vortex beams in nonlinear media.

CD44 targeting nanodrug based on chondroitin sulfate for melanoma therapy by inducing mitochondrial apoptosis pathways.

Neovascularization is crucial to the occurrence and progression of tumors, and the development of antiangiogenic drugs has essential theoretical value and clinical significance. However, antiangiogenesis therapy alone cannot meet the needs of tumor therapy. Meanwhile, polysaccharides are ideal drug carriers with promising applications in drug modification and delivery. In this research, we developed a novel redox and acid sensitive nanodrug (CDDP-CS-Cys-EA, CCEA) composed of chondroitin sulfate (CS), antiangiogenic peptide (endostatin2-alft1, EA) and chemotherapeutic drug (cisplatin, CDDP). CCEA exhibited redox and acid responsiveness, better blood hemocompatibility (hemolysis rate < 5 %), the ability to target tumors (CD44-mediated endocytosis), and strong antiangiogenesis and antitumor characteristics in vitro. Moreover, CCEA showed excellent antitumor activity and low toxicity in B16 xenograft mice. It also has been confirmed that CCEA induced tumor cell apoptosis through promoting the expression of Bax, suppressing the expression of Bcl-2, decreasing mitochondrial membrane potential, releasing cytochrome C (Cyto C), and enhancing the activities of Caspase 9 and Caspase 3. The results of this paper provided a theoretical basis and insight for the development of antitumor drugs.

Vaginal Infections during Pregnancy Increase Breast Milk Microbiome Alpha Diversity and Alter Taxonomic Composition.

We previously reported that breast milk from women with (W) or without (WO) vaginal yeast infection during pregnancy differs in its immunological and antimicrobial properties, especially against pathogenic vaginal Candida sp.. Here, we investigated the differences in microbiota profiles of breast milk from these groups. Seventy-two breast milk samples were collected from lactating mothers (W, n=37; WO, n=35). The DNA of bacteria was extracted from each breast milk sample for microbiota profiling by 16S rRNA gene sequencing. Breast milk from the W-group exhibited higher alpha diversity than that from the WO-group across different taxonomic levels of class (P=0.015), order (P=0.011), family (P=0.020), and genus (P=0.030). Compositional differences between groups as determined via beta diversity showed marginal differences at taxonomic levels of phylum (P=0.087), family (P=0.064), and genus (P=0.067). The W-group showed higher abundances of families Moraxellaceae (P=0.010) and Xanthomonadaceae (P=0.008), and their genera Acinetobacter (P=0.015), Enhydrobacter (P=0.015), and Stenotrophomonas (P=0.007). Meanwhile, the WO-group showed higher abundances of genus Staphylococcus (P=0.046) and species Streptococcus infantis (P=0.025). This study shows that, although breast milk composition is affected by vaginal infection during pregnancy, this may not pose a threat to infant growth and development.

Vortex Solitons in Quasi-Phase-Matched Photonic Crystals.

We report solutions for stable compound solitons in a three-dimensional quasi-phase-matched photonic crystal with the quadratic (χ^{(2)}) nonlinearity. The photonic crystal is introduced with a checkerboard structure, which can be realized by means of the available technology. The solitons are built as four-peak vortex modes of two types, rhombuses and squares (intersite- and onsite-centered self-trapped states, respectively). Their stability areas are identified in the system's parametric space (rhombuses occupy an essentially broader stability domain), while all bright vortex solitons are subject to strong azimuthal instability in uniform χ^{(2)} media. Possibilities for experimental realization of the solitons are outlined.

Review: Application of chitosan and its derivatives in medical materials.

Chitin is a natural polymeric polysaccharide extracted from marine crustaceans, and chitosan is obtained by removing part of the acetyl group (usually more than 60 %) in chitin's structure. Chitosan has attracted wide attention from researchers worldwide due to its good biodegradability, biocompatibility, hypoallergenic and biological activities (antibacterial, immune and antitumor activities). However, research has shown that chitosan does not melt or dissolve in water, alkaline solutions and general organic solvents, which greatly limits its application range. Therefore, researchers have carried out extensive and in-depth chemical modification of chitosan and prepared a variety of chitosan derivatives, which have expanded the application field of chitosan. Among them, the most extensive research has been conducted in the pharmaceutical field. This paper summarizes the application of chitosan and chitosan derivatives in medical materials over the past five years.

Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits.

Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.

Glycol-Split Heparin-Linked Prodrug Nanoparticles Target the Mitochondrion Apparatus for Cancer Metastasis Treatment.

The progression and metastasis of solid tumors rely strongly on neovascularization. However, angiogenesis inhibitors alone cannot meet the needs of tumor therapy. This study prepared a new drug conjugate (PTX-GSHP-CYS-ES2, PGCE) by combining polysaccharides (heparin without anticoagulant activity, GSHP), chemotherapeutic drugs (paclitaxel, PTX), and antiangiogenic drugs (ES2). Furthermore, a tumor-targeted prodrug nanoparticle delivery system is established. The nanoparticles appear to accumulate in the mitochondrial of tumor cells and achieve ES2 and PTX release under high glutathione and acidic environment. It has been confirmed that PGCE inhibited the expression of multiple metastasis-related proteins by targeting the tumor cell mitochondrial apparatus and disrupting their structure. Furthermore, PGCE nanoparticles inhibit migration, invasion, and angiogenesis in B16F10 tumor-bearing mice and suppress tumor growth and metastasis in vitro. Further in vitro and in vivo experiments show that PGCE has strong antitumor growth and metastatic effects and exhibits efficient anti-angiogenesis properties. This multi-targeted nanoparticle system potentially enhances the antitumor and anti-metastatic effects of combination chemotherapy and antiangiogenic drugs.

A high-quality genome compendium of the human gut microbiome of Inner Mongolians.

Metagenome-based resources have revealed the diversity and function of the human gut microbiome, but further understanding is limited by insufficient genome quality and a lack of samples from typically understudied populations. Here we used hybrid long-read PromethION and short-read HiSeq sequencing to characterize the faecal microbiota of 60 Inner Mongolian individuals (n = 180 samples over three time points) who were part of a probiotic yogurt intervention trial. We present the Inner Mongolian Gut Genome catalogue, comprising 802 closed and 5,927 high-quality metagenome-assembled genomes. This approach achieved high genome continuity and substantially increased the resolution of genomic elements, including ribosomal RNA operons, metabolic gene clusters, prophages and insertion sequences. Particularly, we report the ribosomal RNA operon copy numbers for uncultured species, over 12,000 previously undescribed gut prophages and the distribution of insertion sequence elements across gut bacteria. Overall, these data provide a high-quality, large-scale resource for studying the human gut microbiota.

Spraying compound probiotics improves growth performance and immunity and modulates gut microbiota and blood metabolites of suckling piglets.

One factor that shapes the establishment of early neonatal intestinal microbiota is environmental microbial exposure, and probiotic application has been shown to promote health and growth of piglets. Thus, this study hypothesized that environmental probiotic application in early days of life would be beneficial to newborn piglets. This study aimed to investigate the effect of spraying a compound probiotic fermented liquid (CPFL) into the living environment of piglets on their early growth performance and immunity. This work included 68 piglets, which were randomized into probiotic and control groups. Blood and fecal samples were collected at 0, 3, 7, 14, and 21 days of age. Spraying CPFL significantly reshaped the microbiota composition of the delivery room environment, increased piglets' daily weight gain and weaning weight (P<0.001), and modulated piglets' serum cytokine levels (increases in IgA, IgG, and IL-10; decrease in IFN-γ; P<0.05 in each case) in piglets. Additionally, spraying CPFL during early days of life modified piglets' gut microbiota structure and diversity, increased the abundance of some potentially beneficial bacteria (such as Bacteroides uniformis, Butyricimonas virosa, Parabacteroides distasonis, and Phascolarctobacterium succinatutens) and decreased the abundance of Escherichia coli (P<0.05). Interestingly, CPFL application also significantly enhanced the gut microbial bioactive potential and levels of several serum metabolites involved in the metabolism of vitamins (B2, B3, B6, and E), medium/long-chain fatty acids (caproic, tetradecanoic, and peptadecanoic acids), and dicarboxylic acids (azelaic and sebacic acids). Our study demonstrated that spraying CPFL significantly could improve piglets' growth performance and immunity, and the beneficial effects are associated with changes in the gut microbiota and host metabolism. Our study has provided novel data for future development of probiotic-based health-promoting strategies and expanded our knowledge of probiotic application in animal husbandry.

Bifidobacterium lactis Probio-M8 improves bone metabolism in patients with postmenopausal osteoporosis, possibly by modulating the gut microbiota.

PURPOSE: Postmenopausal osteoporosis (PMO) is usually managed by conventional drug treatment. However, prolonged use of these drugs cause side effects. Gut microbiota may be a potential target for treatment of PMO. This work was a three-month intervention trial aiming to evaluate the added effect of probiotics as adjunctive treatment for PMO. METHODS: Forty patients with PMO were randomized into probiotic (n = 20; received Bifidobacterium animalis subsp. lactis Probio-M8 [Probio-M8], calcium, calcitriol) and placebo (n = 20; received placebo material, calcium, calcitriol) groups. The bone mineral density of patients was measured at month 0 (0 M; baseline) and month 3 (3 M; after three-month intervention). Blood and fecal samples were collected 0 M and 3 M. Only 15 and 12 patients from Probio-M8 and placebo groups, respectively, provided complete fecal samples for gut microbiota analysis. RESULTS: No significant change was observed in the bone mineral density of patients at 3 M. Co-administering Probio-M8 improved the bone metabolism, reflected by an increased vitamin D3 level and decreased PTH and procalcitonin levels in serum at 3 M. Fecal metagenomic analysis revealed modest changes in the gut microbiome in both groups at 3 M. Interestingly, Probio-M8 co-administration affected the gut microbial interactive correlation network, particularly the short-chain fatty acid-producing bacteria. Probio-M8 co-administration significantly increased genes encoding some carbohydrate metabolism pathways (including ABC transporters, the phosphotransferase system, and fructose and mannose metabolism) and a choline-phosphate cytidylyltransferase. CONCLUSIONS: Co-administering Probio-M8 with conventional drugs/supplements was more efficacious than conventional drugs/supplements alone in managing PMO. Our study shed insights into the beneficial mechanism of probiotic adjunctive treatment. REGISTRATION NUMBER OF CLINICAL TRIAL: Chinese Clinical Trial Registry (identifier number: ChiCTR1800019268).