Tip-enhanced Raman spectroscopy (TERS) of supported phospholipid bilayers in an aqueous environment is discussed in this paper. Two bilayer membranes were examined: 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We fabricated alumina- and silver-coated tungsten tips that are very robust in water. There was a large time-dependence in the TERS spectra for the DOPC bilayers, whereas no such time-dependence was observed in the DPPC bilayer spectra under the probe tip. The spectral changes of DOPC bilayers are discussed in terms of the fluidity of the liquid crystalline phase. Time-resolved TERS thus has the potential to characterize inhomogeneity and diffusion in fluidic phospholipid bilayer membranes.

Proton pump inhibitors (PPIs) alter the composition of the intestinal microbiome, exacerbating indomethacin (IND)-induced small intestinal damage. Vonoprazan fumarate inhibits gastric acid secretion using a different mechanism from PPIs. We investigated the effects of both drugs on the intestinal microbiome and IND-induced small intestinal damage. We sought to clarify whether PPI-induced dysbiosis and worsening of the damage were due to a specific drug class effect of PPIs. Rabeprazole administration increased operational taxonomic unit numbers in the small intestines of C57BL/6 J mice, whereas the difference was not significant in the vonoprazan-treated group but exhibited a trend. Permutational multivariate analysis of variance of the unweighted UniFrac distances showed significant differences between vehicle- and vonoprazan- or rabeprazole-treated groups. L. johnsonii was the predominant microbial species, and the population ratio decreased after vonoprazan and rabeprazole administration. The vonoprazan- and rabeprazole-treated groups showed increased IND-induced damage. This high sensitivity to IND-induced damage was evaluated by transplantation with contents from the small intestine of mice treated with either vonoprazan or rabeprazole. Supplementation of L. johnsonii orally in mice treated with rabeprazole and vonoprazan prevented the increase in IND-induced small intestinal damage. In conclusion, both rabeprazole and vonoprazan aggravated NSAID-induced small intestinal injury by reducing the population of L. johnsonii in the small intestine via suppressing gastric acid secretion.

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Gliadin, a component of wheat gluten known to be an important factor in the etiology of celiac disease, is related to several other diseases through its enhancing effect on intestinal paracellular permeability. We investigated the significance of gliadin in non-steroidal anti-inflammatory drug (NSAID)-induced small-intestinal damage in mice. 7-week-old C57BL/6 male mice were divided into the following groups: standard diet group, in which mice were fed with wheat-containing standard rodent diet (CE-2); gluten-free diet group, in which mice were fed with gluten-free diet (AIN-76A); and gliadin-administered group, in which mice fed with gluten-free diet were administered with gliadin (~250 mg/kg BW). Each group was subdivided into negative, healthy control group and NSAID-treated group. To some mice fed with gluten-free diet and administered with gliadin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was administered for clarification of the significance of EGFR in NSAID-induced small intestinal damage and intestinal permeability. In mice fed with a gluten-free diet, indomethacin or diclofenac induced very mild mucosal damage in the small intestine compared with that in mice fed with a wheat-containing standard diet. Gliadin exacerbated the NSAID-induced small-intestinal damage in mice fed with a gluten-free diet. With the administration of indomethacin, MPO activity, a marker of neutrophil infiltration into the mucosa and mRNA expression level of tumor necrosis factor α and interleukin-1β in the small intestine were higher in the gliadin-administered mice. Gliadin increased the intestinal paracellular permeability without indomethacin administration (4.3-fold) and further increased the permeability after indomethacin administration (2.1-fold). Gliadin induced phosphorylation of epidermal growth factor receptor (EGFR) in small-intestinal tissues, and erlotinib (an EGFR tyrosine kinase inhibitor) attenuated the indomethacin-induced intestinal damage and permeability exacerbated by gliadin, accompanied by inhibition of EGFR phosphorylation. These results suggest that gliadin plays an important role in the induction and exacerbation of NSAID-induced small-intestinal damage, and that increase in intestinal permeability via the EGFR signalling pathway is involved in its mechanism.

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