BackgroundGold 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.ResultsCitrate- 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.ConclusionsAuNPs have promising potential as anti-inflammatory agents; however, their therapeutic applications via the oral route may have a negative impact on the gut microbiota. Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0415-5) contains supplementary material, which is available to authorized users.

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.

Glycated fish protein showed positively biological effects but increased AGEs accumulation in high-fat-diet-fed rats.

Aqueous extracts from Chlorella pyrenoidosa, Spirulina platensis and Synechococcus sp. PCC 7002 showed gut protective potential in vitro and in vivo.

Wheat protein is the most consumed plant protein in our diet, and there is an increased prevalence of wheat/gluten intolerance and adherence to a gluten-free diet in many countries. Despite the known immunodominant effect of undigested gliadin peptides responsible for gluten-related intolerance, it remains unclear if and how gliadin peptides self-assemble into ordered nanostructures during gastrointestinal digestion, as well as their biological impact on the mucus barrier function. In this study, we purified undigestible gliadin peptide nanoparticles (UGPNs) by ultracentrifugation and characterized their structural and physiochemical properties. The results demonstrate that the UGPNs are self-assembled nanostructures generated by cationic amino acids (Lys and Arg)-capped surfactant-like peptides (SLPs), mainly derived from γ-gliadin and α-gliadin. SLPs trigger the concentration-dependent self-assembly driven by β-sheet conformational transitions above their critical aggregation concentration (cac, ∼0.1 mg/mL). UGPNs can easily penetrate the mucus layer in Caco-2/HT29-MTX cocultures with a high P app value (∼5.7 × 10–6 cm/s) and reduce the production and thickness of the mucus layer driven by intestinal epithelial cell damage. Isothermal titration calorimetry and Langmuir monolayer studies indicate that the self-assembled state of UGPNs significantly affects their binding to DPPC/DOPE lipid membrane models. These results highlight the relevance of the self-assembly of gliadin peptides as a trigger of mucosal inflammation-related wheat/gluten intolerance.