RESUMEN
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.
Asunto(s)
Disbiosis/inducido químicamente , Indometacina/efectos adversos , Intestino Delgado/lesiones , Lactobacillus johnsonii/aislamiento & purificación , Inhibidores de la Bomba de Protones/efectos adversos , Animales , Modelos Animales de Enfermedad , Disbiosis/microbiología , Trasplante de Microbiota Fecal , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Indometacina/administración & dosificación , Inyecciones Intraperitoneales , Intestino Delgado/efectos de los fármacos , Intestino Delgado/microbiología , Lactobacillus johnsonii/efectos de los fármacos , Lactobacillus johnsonii/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Inhibidores de la Bomba de Protones/administración & dosificación , Pirroles/administración & dosificación , Pirroles/efectos adversos , ARN Ribosómico 16S/genética , Rabeprazol/administración & dosificación , Rabeprazol/efectos adversos , Análisis de Secuencia de ADN , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversosRESUMEN
In the current study, we screened Lactobacillus strains isolated from the colon of clinically healthy weaned piglets for potential probiotic properties and isolated Lactobacillus. johnsonii L531, which produced high levels of beneficial metabolites (butyric, acetic, and lactic acid) in vitro. We also evaluated the efficacy of this metabolites-producing probiotic in treating Salmonella. Infantis infection. Oral administration of L. johnsonii L531 to newly weaned piglets significantly decreased levels of Salmonella colonization in colonic and jejunal contents, accelerated the clearance of Salmonella in feces after infection, and reduced S. Infantis translocation to the spleen. Pretreatment with SCFAs-promoting probiotic L. johnsonii L531 significantly ameliorated the depletion of SCFAs induced by S. Infantis infection and led to significantly greater weight gain and better feed conversion ratios compared to piglets challenged only with S. Infantis. These data provide further evidence that SCFAs-promoting probiotic L. johnsonii L531 treatment could be a suitable nonantibiotic alternative for controlling Salmonella infection and maintaining metabolic homeostasis, thereby enhancing the gut health of piglets during the critical weaning period.
Asunto(s)
Ácidos Grasos Volátiles/análisis , Intestinos/química , Lactobacillus johnsonii/fisiología , Interacciones Microbianas , Probióticos/uso terapéutico , Salmonella enterica/patogenicidad , Administración Oral , Animales , Carga Bacteriana , Traslocación Bacteriana , Heces/microbiología , Intestinos/microbiología , Lactobacillus johnsonii/aislamiento & purificación , Probióticos/administración & dosificación , Salmonelosis Animal/microbiología , Bazo/microbiología , Porcinos/microbiología , Destete , Aumento de PesoRESUMEN
Bile salt hydrolase (BSH) activity against the bile acid tauro-beta-muricholic acid (T-ß-MCA) was recently reported to mediate host bile acid, glucose, and lipid homeostasis via the farnesoid X receptor (FXR) signaling pathway. An earlier study correlated decreased Lactobacillus abundance in the cecum with increased concentrations of intestinal T-ß-MCA, an FXR antagonist. While several studies have characterized BSHs in lactobacilli, deconjugation of T-ß-MCA remains poorly characterized among members of this genus, and therefore it was unclear what strain(s) were responsible for this activity. Here, a strain of L. johnsonii with robust BSH activity against T-ß-MCA in vitro was isolated from the cecum of a C57BL/6J mouse. A screening assay performed on a collection of 14 Lactobacillus strains from nine different species identified BSH substrate specificity for T-ß-MCA only in two of three L. johnsonii strains. Genomic analysis of the two strains with this BSH activity revealed the presence of three bsh genes that are homologous to bsh genes in the previously sequenced human-associated strain L. johnsonii NCC533. Heterologous expression of several bsh genes in E. coli followed by enzymatic assays revealed broad differences in substrate specificity even among closely related bsh homologs, and suggests that the phylogeny of these enzymes does not closely correlate with substrate specificity. Predictive modeling allowed us to propose a potential mechanism driving differences in BSH activity for T-ß-MCA in these homologs. Our data suggests that L. johnsonii regulates T-ß-MCA levels in the mouse intestinal environment, and that this species may play a central role in FXR signaling in the mouse.
Asunto(s)
Amidohidrolasas/genética , Amidohidrolasas/metabolismo , Lactobacillus johnsonii/aislamiento & purificación , Análisis de Secuencia de ADN/métodos , Ácido Taurocólico/análogos & derivados , Amidohidrolasas/química , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Ciego/microbiología , Clonación Molecular , ADN Bacteriano/genética , Lactobacillus johnsonii/enzimología , Lactobacillus johnsonii/genética , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Filogenia , Especificidad por Sustrato , Ácido Taurocólico/metabolismoRESUMEN
Structural studies of the major glycolipids produced by two Lactobacillus johnsonii (LJ) strains, LJ 151 isolated from intestinal tract of healthy mice and LJ 142 isolated from mice with experimentally induced inflammatory bowel disease (IBD), were performed. Two major glycolipids, GL1 and GL2, were present in lipid extracts from L. johnsonii 142 and 151 strains. Glycolipid GL1 has been identified as ß-D-Glcp-(1â6)-α-D-Galp-(1â2)-α-D-Glcp-diglyceride and GL2 as α-D-Galp-(1â2)-α-D-Glcp-diglyceride. The main fatty acid residues identified by gas-liquid chromatography-mass spectrometry were palmitic, stearic and lactobacillic acids. Besides structural elucidation of the major glycolipids, the aim of this study was to determine the immunochemical properties of these glycolipids and to compare their immunoreactivity to that of polysaccharides obtained from the same strains. Sera from rabbits immunized with bacterial cells possessed much higher serological reactivity with polysaccharides than with glycolipids. Inversely, reactivity of the glycolipids with human sera from patients with IBD was much higher than that determined for the polysaccharides, while reactivity of glycolipids with human sera from healthy individuals was much lower than one measured for the polysaccharides. Results indicate that glycoconjugates from Lactobacillus cell wall act as antigens and may represent new IBD diagnostic biomarkers.