Microbiota-modulating strategies, including probiotic administration, have been tested for the treatment of chronic gastrointestinal diseases despite limited information regarding their mechanisms of action. We previously demonstrated that patients with active celiac disease have decreased duodenal expression of elafin, a human serine protease inhibitor, and supplementation of elafin by a recombinant Lactococcus lactis strain prevents gliadin-induced immunopathology in the NOD/DQ8 mouse model of gluten sensitivity. The commensal probiotic strain Bifidobacterium longum NCC2705 produces a serine protease inhibitor (Srp) that exhibits immune-modulating properties. Here, we demonstrate that B. longum NCC2705, but not a srp knockout mutant, attenuates gliadin-induced immunopathology and impacts intestinal microbial composition in NOD/DQ8 mice. Our results highlight the beneficial effects of a serine protease inhibitor produced by commensal B. longum strains.IMPORTANCE Probiotic therapies have been widely used to treat gastrointestinal disorders with variable success and poor mechanistic insight. Delivery of specific antiinflammatory molecules has been limited to the use of genetically modified organisms, which has raised some public and regulatory concerns. By examining a specific microbial product naturally expressed by a commensal bacterial strain, we provide insight into a mechanistic basis for the use of B. longum NCC2705 to help treat gluten-related disorders.KEYWORDS probiotic, microbiota, gluten, serpin, celiac, commensal M icrobiota-modulating therapies have been tested for the treatment of chronic gastrointestinal diseases and disorders with inconsistent findings. Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit to the host (57). Specific strains have shown modest efficacy in treatment of irritable bowel syndrome (IBS) (1); of complications of inflammatory bowel disease (IBD), such as pouchitis (2); and of celiac disease (CeD), a chronic enteropathy caused by ingestion of gluten-containing cereals in genetically susceptible individuals (3). In particular, a number of strains belonging to the genus Bifidobacterium have been proposed as beneficial supplements for a wide range of health conditions (4). Depletions in bifidobacteria have been noted in patients with CeD (5), and attempts have been made to supplement some strains as a therapy for CeD (3, 6). However, despite great public interest in the clinical use of specific probiotic strains for intestinal

Silica nanoparticles of 12 nm diameter were surface-doped with ca. 350 (TTF-dppz)Yb(III) surface species, containing bis(propylthio)tetrathiafulvenyl[i]dipyrido-[3,2a:2′,3-c]phenazine (TTF-dppz) as an antenna ligand through a surface organometallic chemistry approach. These nanoparticles absorb and emit in the NIR (λ abs = 750 nm, λ em = 983 and 1050 nm) with a lifetime (τ 1 ) of 2.8 μs, similarly to the corresponding Yb(III) molecular complex (λ abs = 750 nm, λ em = 975, 986, 1009, and 1020 nm with τ 1 = 6.93 μs). The silica materials were fully characterized using combined spectroscopic techniques (IR, NMR, UV−vis, luminescence and lifetime), molecular models and isostructural diamagnetic yttrium-containing materials for easier characterization by NMR spectroscopy. Having established the surface structures and photophysical properties of these nanoparticles, we transposed this methodology to larger silica particles with a diameter of ca. 100 nm. These larger nanoparticles have similar photophysical properties and contain ca. 30 000 chromophores, making possible one-photon NIR-to-NIR emission optical microscopy imaging of single nanoparticles.

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Arterial stiffness is increased in children with mild-to-moderate asthma. The association between impaired lung function and increased arterial stiffness suggests that severity of disease translates into detrimental effects on the cardiovascular system.