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Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A leading to the accumulation of globotriaosylceramide (Gb3) and subsequent increase in globotriaosylsphingosine (lyso-Gb3) in different cells and organs, including the gastrointestinal (GI) tract. GI symptoms represent some of the earliest manifestations of FD and significantly impact quality of life. The origin of these symptoms is complex, and the exact mechanisms remain poorly understood. Here, we sought to determine whether lyso-Gb3 contributes to the pathophysiology of GI symptoms associated with FD by examining its effects on mouse colonic ion transport and motility ex vivo using Ussing chambers and organ baths, respectively. Lyso-Gb3 significantly increased colonic baseline short-circuit current (Isc). This increase in Isc was insensitive to inhibition of the cystic fibrosis transmembrane conductance regulator and Na-K-Cl cotransporter 1, suggesting that the increase in Isc is Cl− ion independent. This response was also insensitive to inhibition by the neurotoxin, tetrodotoxin. In addition, pretreatment with lyso-Gb3 did not significantly influence subsequent responses to either veratridine or capsaicin implying that the response to lyso-Gb3 does not involve the enteric nervous system. In terms of colonic motility, lyso-Gb3 did not significantly influence colonic tone, spontaneous contractility, or cholinergic-induced contractions. These data suggest that lyso-Gb3 significantly influences ion transport in mouse colon, but that accumulation of Gb3 may be a prerequisite for the more pronounced disturbances in GI physiology characteristic of FD. NEW & NOTEWORTHY: Fabry disease-associated lyso-Gb3 significantly influences mouse colonic ion transport in a Cl− ion-independent manner. [ABSTRACT FROM AUTHOR]

The gustatory system is responsible for detecting and evaluating the palatability of the various chemicals present in food and beverages. Taste bud cells, located primarily on the tongue, communicate with the gustatory sensory neurons by means of neurochemical signals, transmitting taste information to the brain. It has also been found that the endocannabinoid system (ECS) may modulate food intake and palatability, and that taste bud cells express cannabinoid receptors. The purpose of this study was to investigate the expression of cannabinoid and cannabinoid-related receptors in the gustatory cells of the papillae vallatae and foliatae of ten piglets. Specific antibodies against the cannabinoid receptors (CB1R and CB2R), G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) were applied on cryosections of lingual tissue; the lingual tissue was also processed using Western blot analysis. Cannabinoid and cannabinoid-related receptors were found to be expressed in the taste bud cells and the surrounding epithelial cells. The extra-papillary epithelium also showed strong immunolabeling for these receptors. The results showed that these receptors were present in both the taste bud cells and the extra-gustatory epithelial cells, indicating their potential role in taste perception and chemesthesis. These findings contributed to understanding the complex interactions between cannabinoids and the gustatory system, highlighting the role of the ECS within taste perception and its potential use in animal production in order to enhance food intake. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a multifactorial condition with heterogeneous pathophysiology, including intestinal permeability alterations. The aim of the present study was to assess the ability of a probiotic blend (PB) consisting of two Lactiplantibacillus plantarum strains (CECT7484 and CECT7485) and one strain of Pediococcus acidilactici (CECT7483) to recover the permeability increase induced by mediators from IBS mucosal biopsies and to highlight the underlying molecular mechanisms. Twenty-one IBS patients diagnosed according to ROME IV criteria (11 IBS-D and 10 IBS-M) and 7 healthy controls were enrolled. Mucosal mediators spontaneously released by IBS and HC biopsies were collected and incubated with/without the PB (10 4 and 10 6 CFU/ml). Paracellular permeability was assessed by evaluating the amount of sulfonic-acid-conjugated to fluorescein passing through the Caco-2 monolayer. RNA was extracted from Caco-2 cells and used to perform qPCR analyses, to evaluate the expression of ZO-1 and β-actin, and RNAseq to evaluate the transcriptomic profile. Untargeted metabolomics was used to characterize metabolites produced by the PB. The PB significantly reduced paracellular permeability after 3 h of incubation. Both doses of the PB significantly recovered the increase in paracellular permeability induced by IBS mediators. qPCR analyses showed that both doses of the PB co-incubated with IBS mediators induced a significant increase in beta-actin expression compared to IBS mediators alone. Concerning IBS subtypes, the high dose of the PB recovered the increase of permeability induced by IBS-D mediators. Transcriptomic analyses, confirmed by qPCR, showed that the high dose of the PB significantly increased CYP1A1 compared to IBS mediators alone. The PB produced a high amount of indole-3-lactic acid. The PB recovers the permeability increase induced by IBS mediators inducing the up-regulation of β-actin. In addition, the PB up-regulates the expression of CYP1A1, known to be involved in the metabolism of xenobiotics, possibly through the production of the indole-3-lactic acid.