Microalgae polysaccharides exert antioxidant and anti-inflammatory protective effects on human intestinal epithelial cells in vitro and dextran sodium sulfate-induced mouse colitis in vivo.

Microalgae polysaccharides (MAPS) have emerged as novel prebiotics, but their direct effects on intestinal epithelial barrier are largely unknown. Here, MAPS isolated from Chlorella pyrenoidosa, Spirulina platensis, and Synechococcus sp. PCC 7002 were characterized as mainly branched heteropolysaccharides, and were bioavailable to Caco-2 cells based on fluorescein isothiocyanate labeling and flow cytometry analysis. These MAPS were equally effective to scavenge hydroxyl and superoxide radicals in vitro and to attenuate the H2O2-, dextran sodium sulfate-, tumor necrosis factor α-, and interleukin 1ß-induced burst of intracellular reactive oxygen species and mitochondrial superoxide radicals, interleukin-8 production, cyclooxygenase-2 and inducible nitric oxide synthase expression, and/or tight junction disruption in polarized Caco-2 cells. MAPS and a positive drug Mesalazine were intragastrically administered to C57BL/6 mice daily for 7 d during and after 4-d dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed equivalent anti-colitis efficacies of MAPS and Mesalazine, and based on biochemical analysis of colonic tight junction proteins, goblet cells, mucin 2 and trefoil factor 3 transcription, and colonic and peripheral pro-inflammatory cytokines, MAPS alleviated dextran sodium sulfate-induced intestinal epithelial barrier dysfunction, and their activities were even superior than Mesalazine. Overall, MAPS confer direct antioxidant and anti-inflammatory protection to intestinal epithelial barrier function.

Gum Arabic-Stabilized Ferric Oxyhydroxide Nanoparticles for Efficient and Targeted Intestinal Delivery of Bioavailable Iron.

Nanostructured iron(III) compounds are promising food fortificants with desirable iron bioavailability and food compatibility. Here, gum arabic (GA) solubilized 252 mg of iron(III) per g at neutral pH in the form of GA-stabilized ferric oxyhydroxide nanoparticles (GA-FeONPs) with Z-average size of 142.7 ± 5.9 nm and ζ-potential of -20.50 ± 1.25 mV. Calcein-fluorescence-quenching assay revealed well-absorbed iron from GA-FeONPs by polarized Caco-2 cells due to efficient macropinocytic internalization and asialoglycoprotein receptor-mediated specific endocytosis facilitated by the polypeptide and arabinogalactan fractions of GA, respectively, with endocytosed GA-FeONPs being in part basolaterally transcytosed and in another part degraded into cellular labile iron pool. GA-FeONPs showed good colloidal stability under varied pH, gastrointestinal, thermal processing, and spray/freeze drying conditions and displayed remarkably weaker pro-oxidant activity than FeSO4 in glyceryl trilinoleate emulsion (P < 0.05). Oral pharmacokinetics unveiled desirable iron bioavailability of GA-FeONPs relative to FeSO4, i.e., 124.27 ± 5.91% in aqueous solution and 161.64 ± 5.01% in milk. Overall, GA-FeONPs are a promising novel iron fortificant with food-compatible, efficient, and targeted intestinal iron delivery and sustained iron-release properties.

Enhancing the AI-2/LuxS quorum sensing system in Lactiplantibacillus plantarum: Effect on the elimination of biofilms grown on seafoods.

The biofilm clustered with putrefying microorganisms and seafood pathogens could cover the surface of aquatic products that pose a risk to cross-contaminating food products or even human health. Fighting biofilms triggers synchronous communication associated with microbial consortia to regulate their developmental processes, and the enhancement of the quorum sensing system in Lactiplantibacillus plantarum can serve as an updated starting point for antibiofilm-forming strategies. Our results showed that the exogenous 25 mM L-cysteine induced a significant strengthening in the AI-2/LuxS system of Lactiplantibacillus plantarum SS-128 along with a stronger bacteriostatic ability, resulting in an effective inhibition of biofilms formed by the simplified microbial consortia constructed by Vibrio parahaemolyticus and Shewanella putrefaciens grown on shrimp and squid surfaces. The accumulation of AI-2 allowed the suppression of the expression of biofilm-related genes in V. parahaemolyticus under the premise of L. plantarum SS-128 treatment, contributing to the inhibition effect. In addition, strengthening the AI-2/LuxS system is also conducive to eliminating preexisting biofilms by L. plantarum SS-128. This study suggests that the enhancement of the AI-2/LuxS system of lactic acid bacteria enables the regulation of interspecific communication within biofilms to be a viable tool to efficiently reduce and eradicate potentially harmful biofilms from aquatic product sources, opening new horizons for combating biofilms.

Antioxidant and anti-inflammatory protective effects of yellowtail (Seriola quinqueradiata) milt hydrolysates on human intestinal epithelial cells in vitro and dextran sodium sulphate-induced mouse colitis in vivo.

Milt is an underutilized fish processing by-product containing valuable nutrients for human health. Here, a gastrointestinal hydrolysate of degreased yellowtail (Seriola quinqueradiata) milt contained 70.6% arginine-rich protein, 20% nucleic acids, 7.1% minerals and 2.3% carbohydrates. Yellowtail milt hydrolysates (YMH) effectively attenuated the H2O2-induced burst of intracellular reactive oxygen species, plasma membrane impairment, loss of cell viability, interleukin 8 production and the expression of claudin-4 and occludin in Caco-2 cells with its protein fraction playing a greater antioxidant role than its nucleic acid fraction. YMH also significantly counteracted the tumor necrosis factor α- and interleukin 1ß-stimulated interleukin 8 production and cyclooxygenase-2 and inducible nitric oxide synthase expression in Caco-2 cells and inhibited the production of nitric oxide and proinflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells depending on its protein fraction, rather than its nucleic acid fraction. YMH and a positive drug 5-aminosalicylic acid were intragastrically administered to C57BL/6 mice daily for 7 days during and after 4-day dextran sodium sulphate exposure. Based on clinical signs, colon histopathology and biochemical analysis of colonic tight junction proteins, mucus compositions and goblet cells, YMH ameliorated mouse colitis symptoms and intestinal epithelial barrier dysfunction more effectively than 5-aminosalicylic acid. According to myeloperoxidase activity, proinflammatory cytokines and NF-κB, YMH and 5-aminosalicylic acid exerted equivalent inhibitory effects on colonic and systemic inflammation. Overall, YMH have considerable antioxidant and anti-inflammatory efficacies to maintain gut health.

Dissecting of the AI-2/LuxS Mediated Growth Characteristics and Bacteriostatic Ability of Lactiplantibacillus plantarum SS-128 by Integration of Transcriptomics and Metabolomics.

Lactiplantibacillus plantarum could regulate certain physiological functions through the AI-2/LuxS-mediated quorum sensing (QS) system. To explore the regulation mechanism on the growth characteristics and bacteriostatic ability of L. plantarum SS-128, a luxS mutant was constructed by a two-step homologous recombination. Compared with ΔluxS/SS-128, the metabolites of SS-128 had stronger bacteriostatic ability. The combined analysis of transcriptomics and metabolomics data showed that SS-128 exhibited higher pyruvate metabolic efficiency and energy input, followed by higher LDH level and metabolite overflow compared to ΔluxS/SS-128, resulting in stronger bacteriostatic ability. The absence of luxS induces a regulatory pathway that burdens the cysteine cycle by quantitatively drawing off central metabolic intermediaries. To accommodate this mutations, ΔluxS/SS-128 exhibited lower metabolite overflow and abnormal proliferation. These results demonstrate that the growth characteristic and metabolism of L. plantarum SS-128 are mediated by the AI-2/LuxS QS system, which is a positive regulator involved in food safety. It would be helpful to investigate more bio-preservation control potential of L. plantarum, especially when applied in food industrial biotechnology.

Phycocyanin ameliorates mouse colitis via phycocyanobilin-dependent antioxidant and anti-inflammatory protection of the intestinal epithelial barrier.

Phycocyanin is a typical microalgal active compound with antioxidant and anti-inflammatory efficacy, and the pigment moiety phycocyanobilin has been recently proposed as its active structural component. Here, to explore the structural basis for phycocyanin's intestinal protective action, we evaluated the therapeutic effects and mechanism of action of phycocyanin and phycocyanobilin in dextran sodium sulphate (DSS)-induced colitis mice and in Caco-2 and RAW 264.7 cells. Phycocyanobilin was obtained by solvothermal alcoholysis of phycocyanin and characterized by spectroscopy and mass spectrometry methods. Phycocyanin, phycocyanobilin and a positive drug mesalazine were intragastrically administered to C57BL/6 mice daily for 7 days during and after 4-day DSS exposure. Clinical signs and colon histopathology revealed that phycocyanin and phycocyanobilin had an equivalent anti-colitis efficacy that was even superior to mesalazine. Based on biochemical analysis of colonic tight junction proteins, mucus compositions and goblet cells, and colonic and peripheral proinflammatory cytokines, phycocyanin and phycocyanobilin displayed equivalent intestinal epithelial barrier-protecting and anti-inflammatory potential that was evidently superior to that of mesalazine. Flow cytometry analysis of phycocyanobilin fluorescence in Caco-2 cells unveiled a similar uptake efficacy of phycocyanin and phycocyanobilin by intestinal epithelial cells. According to lactic dehydrogenase release, 2',7'-dichlorodihydrofluorescein fluorescence and methylthiazolyldiphenyl-tetrazolium bromide assay in Caco-2 cells, phycocyanin and phycocyanobilin could equally and effectively protect the intestinal epithelial barrier from oxidant-induced disruption. Phycocyanin and phycocyanobilin also showed equivalent anti-inflammatory effects in tumor necrosis factor-α-stimulated Caco-2 cells and in lipopolysaccharides- and tumor necrosis factor-α-activated RAW264.7 cells. Overall, our results demonstrate the phycocyanobilin-dependent anti-colitis role of phycocyanin via antioxidant and anti-inflammatory mechanisms.

Polyphosphates as an effective vehicle for delivery of bioavailable nanoparticulate iron(III).

Polyphosphates are widely used food additives with the potential to increase iron bioavailability but chemical nature of their soluble complexes with iron remains largely unknown. Here, pyrophosphate, tripolyphosphate, hexametaphosphate and ∼25-chain-length polyphosphate solubilized 896, 896, 1120 and 1344 mg Fe(III) per g, respectively, at neutral pH by mediating the formation of highly-negatively-charged ferric hydroxide-polyphosphate nanoparticles (PolyP-FeONPs). PolyP-FeONPs displayed fading yellow color with increasing initial dissolved P/Fe ratio ((P/Fe)init) and decreasing polyphosphate length due to rising proportion of Fe(III)-phosphate bonds, and specifically, pyrophosphate resulted colorless PolyP-FeONPs at (P/Fe)init ≥ 4. PolyP-FeONPs had weak pro-oxidant activity in glyceryl trilinoleate emulsion and good colloidal stability under spray/freeze-drying and gastrointestinal conditions. Serum iron kinetics in rats revealed sustained iron release and ∼170% iron bioavailability of oral PolyP-FeONPs relative to FeSO4. Calcein-fluorescence-quenching assay in polarized Caco-2 cells unveiled divalent-metal-transporter-1-independent and macropinocytosis-dependent iron uptake from PolyP-FeONPs. This study helps develop food-compatible, highly-bioavailable and sustained-release iron preparations.

Encapsulation of oyster protein hydrolysates in nanoliposomes: Vesicle characteristics, storage stability, in vitro release, and gastrointestinal digestion.

In this study, oyster protein hydrolysates (OPH) were obtained from oyster meat by hydrolysis using animal complex proteases and then encapsulated in nanoliposomes. The physicochemical properties, stability, and digestive characteristics of OPH-loaded nanoliposomes were evaluated. The average size and zeta potential ranged from 95.64 to 102.39 nm and from -47.36 to -36.43 mV, respectively. Liposomes containing 4 mg/mL OPH had the highest encapsulation efficiency (74.53%). Fourier transform infrared spectroscopy analysis showed that effective ionic complexation and hydrogen bonding existed between phospholipid and peptides. The liposomes exhibited the highest stability when stored at 4 °C. Liposomal encapsulation may protect the antioxidant peptides in OPH during storage and simulated digestion. The nanoliposomes were not hydrolyzed and the structural integrity was maintained in gastric digestion, but exhibited lower stability in the intestinal phase. A prolonged release of OPH from nanoliposomes was also observed as compared with free OPH. Liposome containing protein hydrolysates may be used as a formula in functional foods. PRACTICAL APPLICATION: This study provides some useful information on the application of oyster protein hydrolysates or peptides in functional foods. The incorporation into liposomes may protect the hydrolysates against harsh conditions during storage and digestion, and also prolong the release time.

Orthophosphate affects iron(III) bioavailability via a mechanism involving stabilization and delivery of ferric hydroxide-phosphate nanoparticles.

Orthophosphate is endogenously present in gastrointestinal fluids and increasingly ingested as additives in processed foods. However, its effect and mechanism of action on iron bioavailability remains controversial and largely unknown. Here, at initial dissolved P/Fe ratios ((P/Fe)init) ≥ 0.6, orthophosphate completely prevents hydrolytic Fe(III) precipitation at neutral pH by mediating the formation of negatively-charged (≈-29 mV ζ-potential) ferric hydroxide-phosphate nanoparticles (Fe(OH)P-NPs) consisting of ≈3.8-nm-diameter monomers. Fe(OH)P-NPs have decreased size and Fe/P ratio with increasing (P/Fe)init. Acidic pH and balanced salts in intestinal fluid counteract orthophosphate-mediated Fe(III) solubilization by weakening colloidal stability of Fe(OH)P-NPs. Protein digests from egg white, whey, casein, and fish muscle aid Fe(III) solubilization in intestinal fluid by stabilizing Fe(OH)P-NPs with casein digest displaying the highest Fe(III)-solubilizing capacity, and in calcein-fluorescence-quenching assay, deliver nanoparticulate Fe(III) to polarized Caco-2 cells via divalent-metal-transporter-1-dependent or endocytic pathways. Overall, our study provides a new paradigm for understanding orthophosphate's role in iron bioavailability.

Collagen Hydrolysate Corrects Anemia in Chronic Kidney Disease via Anti-Inflammatory Renoprotection and HIF-2α-Dependent Erythropoietin and Hepcidin Regulation.

Anemia is a common chronic kidney disease (CKD) complication contributing to increased morbidity and mortality. Collagen-based traditional Chinese nutraceuticals have long been used in antianemic therapies. This study aims to investigate the therapeutic effectiveness of porcine collagen hydrolysate (CH) and its underlying mechanism in the treatment of renal anemia by using adenine-induced CKD mice, RAW264.7 macrophages, and HepG2 hepatoma cells, with prolyl-hydroxyproline as a reference compound for collagen-derived hydroxyproline-containing di-/tripeptides. CH was found to alleviate renal filtering dysfunction, systemic and kidney inflammation, liver hepcidin overproduction and anemia and to increase erythropoietin production and hypoxia inducible factor (HIF)-2α stability in liver and kidney in CKD mice. Prolyl-hydroxyproline exerted direct anti-inflammatory effects on lipopolysaccharide-activated macrophages and elicited stimulating and inhibiting activities on erythropoietin expression and hepcidin overproduction, respectively, in HepG2 cells by HIF-2α activation. Overall, CH was effective in correcting renal anemia via anti-inflammatory renoprotection and HIF-2α-dependent erythropoietin and hepcidin regulation.

Stabilization and delivery of bioavailable nanosized iron by fish sperm DNA.

Nanosized iron is a promising candidate as an iron fortificant due to its good solubility and bioavailability. Here, ferric hydrolysis in the presence of salmon/herring sperm DNA yielded irregularly shaped, highly negatively charged DNA-stabilized ferric oxyhydroxide nanoparticles (DNA-FeONPs) aggregated from 2-4 nm primary spherical monomers, in which phosphodioxy groups of the DNA backbone served as the iron-nucleation sites with high molecular weight (>500 bp), double-stranded winding, and acidic environmental pH disfavoring DNA's iron-loading capacity. The calcein fluorescence-quenching kinetics of polarized Caco-2 cells revealed the involvement of divalent transporter 1, macropinocytosis and nucleolin-mediated endocytosis in intestinal iron absorption from DNA-FeONPs with low molecular weight (<500 bp) favoring the performance of DNA in aiding iron absorption. In anemic rats, dietary DNA-FeONPs showed >80% relative iron bioavailability compared to FeSO4 as per hemoglobin regeneration efficiencies and delivered intestinally available nanosized iron, as determined by luminal iron speciation analysis. Overall, fish sperm DNA is promising in stabilizing and delivering bioavailable nanosized iron.

Chondroitin sulfate and its nanocomposites with protamine or chitosan stabilize and deliver available nanosized iron.

Nanostructured iron (III) compounds are promising candidates for iron fortification applications due to their good solubility, bioavailability, and redox inertia. The current study synthesized ferric oxyhydroxide nanoparticles (FeONPs) based on chondroitin sulfate (ChS) and its nanocomposites with protamine sulfate (PS) or chitosan (CS) in neutral aqueous solution under ambient conditions, and evaluated their iron availability to polarized human intestinal epithelial (Caco-2) cells. Ultraviolet-visible spectroscopy, dynamic light scattering, transmission electron microscopy and energy-dispersive X-ray spectroscopy showed that ChS-FeONPs were wave-like anionic particles where FeONPs attached on the polysaccharide chains and PS/ChS-FeONPs and CS/ChS-FeONPs were irregular anionic nanoparticles where FeONPs scattered across the entire region. The calcein-fluorescence-quenching assay in polarized Caco-2 cells showed good iron uptake from ChS-FeONPs, PS/ChS-FeONPs and CS/ChS-FeONPs mainly via endocytosis, with the latter two exhibiting better iron absorption. Overall, our study provides a more facile and greener alternative route to synthesize the bioavailable nano-sized iron.

Microalgae aqueous extracts exert intestinal protective effects in Caco-2 cells and dextran sodium sulphate-induced mouse colitis.

Microalgae are emerging as a good source of natural nutraceuticals. Here, we examined the intestinal protective effects of microalgae aqueous extracts (MAEs) from Chlorella pyrenoidosa, Spirulina platensis, and Synechococcus sp. PCC 7002 in human intestinal epithelial Caco-2 cells and dextran sodium sulphate (DSS)-induced colitis in C57BL/6 mice. MAEs displayed intestinal barrier-protective activities in Caco-2 cells by increasing the expression of heat shock protein (Hsp)-27 and tight junction proteins of occludin and claudin-4 and attenuating the H2O2-induced intracellular reactive oxygen species production, plasma membrane impairment and apoptosis. They also showed anti-inflammatory potential in tumor necrosis factor (TNF)-α-, interleukin (IL)-1ß- and H2O2-stimulated Caco-2 cells by suppressing the secretion of IL-8 and the expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). The 8 d daily intragastric administration of MAEs during and after 4 d DSS exposure effectively alleviated colitis symptoms of weight loss, diarrhea, rectal bleeding, and colon shortening and histopathology, protected intestinal barrier function by increasing colonic Hsp-25, occludin and claudin-4, and attenuated colonic and systemic inflammation by suppressing colonic myeloperoxidase activity, production of TNF-α, IL-1ß and IL-6, expression of COX-2 and iNOS, and peripheral leukocytosis, monocytosis and granulocytosis. Microalgae can thus serve as a functional food to maintain gut health.

Platinum Nanoparticles As A Therapeutic Agent Against Dextran Sodium Sulfate-Induced Colitis In Mice.

PURPOSE: This study aimed to evaluate the anti-colitis potential of platinum nanoparticles (PtNPs). MATERIALS AND METHODS: 5-, 30- and 70-nm PtNPs were administered to C57BL/6 mice once daily by intragastric gavage for 8 d during and after 5-d dextran sodium sulfate treatment. RESULTS: According to body weight change, stool blood and consistency, and colon length and histopathology, PtNPs size-dependently alleviated DSS-induced murine colitis. PtNPs enhanced gut-barrier function by upregulating the colonic expressions of heat-shock protein 25 and tight junction proteins. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of white blood cells, PtNPs attenuated colonic and systemic inflammation. By suppressing lipopolysaccharide-triggered production of proinflammatory mediators, including nitric oxide, tumor necrosis factor-α and interleukin-6, PtNPs exerted direct anti-inflammatory activities in RAW264.7 macrophages through a mechanism involving intracellular reactive oxygen species scavenging and Toll-like receptor 4/NF-κB signaling suppression. High-throughput 16S rRNA sequencing of fecal samples unveiled that PtNPs induced gut dysbiosis by unfavorably altering α-diversity, Firmicutes/Bacteroidetes ratio, and richness of certain specific bacteria. CONCLUSION: PtNPs are a promising anti-colitis agent, but may negatively impact gut-microbiota.

Effects of High Pressure Modification on Conformation and Digestibility Properties of Oyster Protein.

To expand the utilization of oyster protein (OP), the effects of high pressure (100 to 500 MPa) on chemical forces, structure, microstructure, and digestibility properties were investigated. High pressure (HP) treatment enhanced the electrostatic repulsion (from -13.3Control to -27.8HP200 mV) between protein molecules and avoided or retarded the formation of protein aggregates. In addition, the HP treated samples showed uniform distribution and small particle size. The changes in electrostatic interaction and particle size contributed to the improvement of solubility (from 10.53%Control to 19.92%HP500 at pH 7). The stretching and unfolding of protein were modified by HP treatment, and some internal hydrophobic groups and -SH groups were exposed. HP treatment modified the secondary structure of OP. The treated samples contained less α-helix and ß-sheet structures, whereas the proportions of ß-sheet and random coil structures were increased. The treated samples have high digestibility in the stomach (from 26.3%Control to 39.5%HP500) and in the total digestive process (from 62.1%Control to 83.7%HP500). In addition, the total digestive production showed higher percentages of small peptides (<1 kDa) after HP treatment. The protein solubility and digestibility were increased after HP treatment, and high solubility and high digestibility might increase the chance that OP become a kind of protein supplement.

Catalase-mimetic gold nanoparticles inhibit the antagonistic action of Lactobacillus gasseri toward foodborne enteric pathogens in associative cultures.

Gold nanoparticles (AuNPs) have been previously shown to induce gut dysbiosis during colitis in mice, but the underlying mechanism is not clear yet. Here, we evaluated the effects of AuNPs (5 nm diameter, coated with tannic acid, polyvinylpyrrolidone or citrate) on H2O2 accumulation and pathogen antagonization by an intestinal strain of Lactobacillus gasseri under aerobic cultural conditions. AuNPs (0.65 µg/mL) reduced over 50% of H2O2 accumulation by L. gasseri, and significantly inhibited the antagonistic action of L. gasseri on growth of four foodborne enteric pathogens, i.e. Salmonella enterica serovar Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus in associative cultures.

Protective effect of biogenic polyphosphate nanoparticles from Synechococcus sp. PCC 7002 on dextran sodium sulphate-induced colitis in mice.

Biogenic polyphosphate nanoparticles (BPNPs) from Synechococcus sp. PCC 7002 have been found to exhibit intestinal protective potential in vitro and ex vivo. The aim of this study was to evaluate the in vivo intestinal protective effect of BPNPs in experimental colitis. BPNPs were intragastrically administered to C57BL/6 mice daily for 9 d during and after 5 d dextran sodium sulfate (DSS) exposure. Based on the body weight, disease activity index, colon length and colon histology, BPNPs effectively ameliorated DSS-induced colitis in mice. According to colonic myeloperoxidase activity, colonic and peripheral proinflammatory cytokines, and hematological parameters, BPNPs alleviated the DSS-induced colonic and systemic inflammation. BPNPs enhanced the intestinal barrier function by upregulating the colonic expressions of heat shock protein 25 and tight junction proteins. By high-throughput sequencing of fecal 16S rRNA, BPNPs were found to maintain gut microbial homeostasis in colitis mice. Overall, BPNPs have a considerable in vivo efficacy to maintain gut health.

Effect of microalgae as iron supplements on iron-deficiency anemia in rats.

Microalgae are potential iron supplements for improving iron deficiency through an unknown mechanism. To analyze the increase in non-heme iron absorption caused by microalgae, six different microalgal feeds were prepared from Spirulina, Chlorella and Synechococcus sp. PCC 7002 as the main source of dietary iron (25 mg kg-1; denoted as H-Sp, H-Ch, and H-Sy, respectively) or as a partial source of dietary iron (5 mg kg-1; denoted as L-Sp, L-Ch, and L-Sy, respectively) to suppress iron-deficiency anemia in rats. The hemoglobin regeneration efficiencies in anemic rats were in the order ferric citrate (34.7 ± 1.8%) < H-Ch (49.9 ± 4.1%) ≈ H-Sy (50.6 ± 5.3%) ≈ L-Sp (46.9 ± 6.2%) ≈ L-Ch (43.1 ± 6.9%) ≈ L-Sy (43.5 ± 2.4%) ≈ FeSO4 (47.2 ± 4.9%) < H-Sp (54.8 ± 5.5%). The percentage content of intestinal nanosized iron in the H-Sp, H-Ch, and H-Sy treatment groups was significantly higher than that in the L-Sp, L-Ch, and L-Sy groups, and was significantly higher in the microalgal diet groups than in the ferric citrate group, providing strong evidence for nanosized iron supplementation from microalgae. Overall, microalgae, especially Spirulina, are functional iron nutritive fortifiers that can supply intestinal nanosized iron.

Siderophore (from Synechococcus sp. PCC 7002)-Chelated Iron Promotes Iron Uptake in Caco-2 Cells and Ameliorates Iron Deficiency in Rats.

Siderophores are iron chelators with low molecular weight secreted by microorganisms. Siderophores have the potential to become natural iron fortifiers. To explore the feasibility of the application of Synechococcus sp. PCC7002-derived siderophores as iron fortifiers, Synechococcus sp. PCC7002, as a carrier, was fermented to produce siderophores. The absorption mechanism and anemia intervention effect of siderophores-chelated iron (SCI) were studied through the polarized Caco-2 Cell monolayers and the rat model of iron-deficiency anemia, respectively. The results indicated that siderophores (from Synechococcus sp. PCC7002) had an enhancing effect on iron absorption in polarized Caco-2 cell monolayers. The main absorption site of SCI was duodenum with pH 5.5, and the absorption methods included endocytosis and DMT1, with endocytosis being dominant. The effect of sodium phytate on SCI was less than that of ferrous sulfate. Therefore, SCI could resist inhibitory iron absorption factors in polarized Caco-2 cell monolayers. SCI showed significantly higher relative bioavailability (133.58 ± 15.42%) than ferrous sulfate (100 ± 14.84%) and ferric citrate (66.34 ± 8.715%) in the rat model. Food intake, hemoglobin concentration, and hematocrit and serum iron concentration of rats improved significantly after Fe-repletion. Overall, this study indicated that siderophores derived from Synechococcus sp. PCC7002 could be an effective and feasible iron nutritive fortifier.

Orally administered gold nanoparticles protect against colitis by attenuating Toll-like receptor 4- and reactive oxygen/nitrogen species-mediated inflammatory responses but could induce gut dysbiosis in mice.

BACKGROUND: Gold nanoparticles (AuNPs) are attracting interest as potential therapeutic agents to treat inflammatory diseases, but their anti-inflammatory mechanism of action is not clear yet. In addition, the effect of orally administered AuNPs on gut microbiota has been overlooked so far. Here, we evaluated the therapeutic and gut microbiota-modulating effects, as well as the anti-inflammatory paradigm, of AuNPs with three different coatings and five difference sizes in experimental mouse colitis and RAW264.7 macrophages. RESULTS: Citrate- and polyvinylpyrrolidone (PVP)-stabilized 5-nm AuNPs (Au-5 nm/Citrate and Au-5 nm/PVP) and tannic acid (TA)-stabilized 5-, 10-, 15-, 30- and 60-nm AuNPs were intragastrically administered to C57BL/6 mice daily for 8 days during and after 5-day dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed more marked anti-colitis effects by oral administration of Au-5 nm/Citrate and Au-5 nm/PVP, when compared to TA-stabilized AuNPs. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of leukocyte and lymphocyte, Au-5 nm/Citrate and Au-5 nm/PVP attenuated colonic and systemic inflammation more effectively than TA-stabilized AuNPs. High-throughput sequencing of fecal 16S rRNA indicated that AuNPs could induce gut dysbiosis in mice by decreasing the α-diversity, the Firmicutes/Bacteroidetes ratio, certain short-chain fatty acid-producing bacteria and Lactobacillus. Based on in vitro studies using RAW264.7 cells and electron spin resonance oximetry, AuNPs inhibited lipopolysaccharide (LPS)-triggered inducible nitric oxide (NO) synthase expression and NO production via reduction of Toll-like receptor 4 (TLR4), and attenuated LPS-induced nuclear factor kappa beta activation and proinflammatory cytokine production via both TLR4 reduction and catalytic detoxification of peroxynitrite and hydrogen peroxide. CONCLUSIONS: AuNPs have promising potential as anti-inflammatory agents; however, their therapeutic applications via the oral route may have a negative impact on the gut microbiota.