The garlic-derived compounds propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO) are metabolites with putative health benefits against intestinal inflammation that may be related to their antioxidant activity. However, the underlying mechanisms remain unclear, and whether PTS-PTSO can promote gut health by altering the microbiota and exert protection against enteric pathogens needs further investigation. Here, we explored the antioxidant activity of PTS-PTSO in murine macrophages in vitro, and in an in vivo model of bacterial infection with the bacterial pathogen Citrobacter rodentium. PTS-PTSO attenuated reactive oxygen species in lipopolysaccharide-stimulated macrophages in a nuclear factor erythroid factor 2-related factor 2 (Nrf2)-dependent manner, decreased nitric oxide levels both in macrophages in vitro and in the sera of mice fed PTS-PTSO, and had putatively beneficial effects on the commensal gut microbiota. Importantly, PTS-PTSO decreased faecal C. rodentium counts, concomitant with upregulation of Nrf2-related genes in colon tissue. Thus, PTS-PTSO mediates Nrf2-mediated antioxidant activity and modulates gut microbiota, which may protect the host against C. rodentium colonization. Our results provide further insight into how PTS-PTSO and related bioactive dietary compounds may reduce enteric infections.
Background/Objectives: Dietary glucose is transported across the intestinal absorptive cell into the systemic circulation by the apically located Na+-dependent glucose transporter 1 (SGLT1, SLC5A1) and basally residing Na+-independent glucose transporter 2 (GLUT2, SLC2A2). Whilst recent experimental evidence has shown that sensing of sweet compounds by the gut-expressed sweet taste receptor T1R2–T1R3 and glucagon-like peptide-2 receptor signalling are components of the pathway controlling SGLT1 expression, little is known about the mechanisms involved in the regulation of GLUT2. In this study, we tested the hypothesis that T1R2–T1R3 and its downstream signalling pathway participate in the regulation of intestinal GLUT2. Methods: We used in vivo and in vitro approaches employing a weaning pig model, a heterologous expression assay, and knockout mice for elucidating the regulation of GLUT2 by luminal sugars. Results: A plant-based sweetener formulation included in piglets’ diet led to a marked increase in GLUT2 expression in piglets’ intestine, compared to controls. The sweeteners that do not activate pig T1R2–T1R3 failed to upregulate GLUT2. There was a significant increase in GLUT2 expression when the sweetener sucralose, which activates T1R2–T1R3, was included in the drinking water of wild-type mice. However, in knockout mice, in which the genes for the sweet receptor subunit T1R3 and the associated G-protein gustducin were deleted, there was no upregulation of GLUT2 expression in response to sucralose supplementation. There was a notable increase in GLUT2 expression in wild-type mice fed a high-carbohydrate diet compared to when maintained on a low-carbohydrate diet. However, in GLP-2 receptor knockout mice kept on the high-carbohydrate diet, there was no enhancement in GLUT2 expression. Conclusions: The experimental evidence suggests that luminal sweet sensing via T1R2–T1R3 and the enteroendocrine-derived GLP-2 are constituents of the regulatory pathway controlling GLUT2 expression.
20 December 2025 in Regulatory Toxicology and Pharmacology
α-Terpineol is a flavoring ingredient that occurs naturally in spices and foods. It has been evaluated by regulatory and scientific expert bodies such as the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1999 and the European Food Safety Authority (EFSA) in 2006 and has been determined safe under the conditions of intended use. To ensure the continued safety of high-usage flavoring ingredients, a 90-day Organization for Economic Co-operation and Development (OECD) 408 and Good Laboratory Practice (GLP) compliant study was conducted in Sprague-Dawley (SD) rats (10/sex/groups) at target dietary intakes to achieve doses of 0, 50, 150 or 500 mg/kg bw/day. There were no unscheduled deaths and no adverse changes in ophthalmological examinations, body weight, food consumption, food efficiency, hematology, serum chemistry, urinalysis parameters and macroscopic and microscopic observations. While not statistically significant, excessive fragmentation of sperm (head and tail separating) was observed in high-dose males, resulting in reduced or zero sperm mobility. Based on the specific sperm abnormalities observed, the no-observed-adverse-effect level (NOAEL) was determined to be the middle dose, 146 mg/kg bw/day for male SD rats and 500 mg/kg bw/day, the highest dose tested, for female SD rats.
Gastrointestinal nematodes (GIN) use flexible life history strategies to maintain their fitness under environmental challenges. Costs incurred by a challenge to one life trait can be recouped by increasing the expression of subsequent life traits throughout their life cycle. Anticipating how parasites respond to the challenge of control interventions is critical for the long-term sustainability of the practice and to further ensure that the parasites withstand favourable adaptive responses. There is currently limited information on whether distinct populations of a GIN species respond to the same environmental challenge in a consistent manner, with similar alterations to their life history strategies or comparable fitness outcomes. This study compared the life history traits and experimental fitness of three distinct Haemonchus contortus isolates exposed to environmental challenges at both the parasitic (i.e., passage through resistant or susceptible sheep) and free-living (i.e., exposure to diverse climatic conditions) life stages. The key findings show that H. contortus maintain their fitness under challenge with isolate-specific alterations to their life history strategies. Further, partial exploration of the H. contortus isolates transcriptomes using cDNA-AFLP methods confirmed disparate expression profiles between them. These results bring fresh insights into our understanding of the non-genetic adaptive processes of GIN that may hinder the efficacy of parasite control strategies.
An in vitro and an in vivo study were conducted to investigate the effects of a blend of cinnamaldehyde, eugenol, and capsicum oleoresin (CEC) on rumen fermentation parameters, animal performance, and methane (CH4) emissions in dairy cows. Continuous culture fermenters (CCF) were utilized to test one of two treatments: (1) CON; no supplementation and (2) CEC supplemented at 0.0125 g/d. The basal diet consisted of grass hay and concentrate (50:50). Supplementation with CEC increased (p < 0.01) total volatile fatty acids (VFA; mM) and decreased (p = 0.02) CH4 concentration compared with CON in vitro. Additionally, protozoa abundance tended (p = 0.07) to decrease in CEC compared with CON. The in vivo experiment utilized forty Holstein-Friesian dairy cows (32% primiparous and 68% multiparous) averaging 163 ± 48 days in milk (DIM) and 38 ± 6.2 kg/d of milk yield (MY). Cows were blocked by parity and randomly assigned to one of two treatments: (1) CON; no supplementation and (2) CEC supplemented at 1.2 g/cow/d. The basal diet consisted of grass hay and concentrate (40:60). Individual CH4 emissions were recorded using the sniffer technique. Dry matter intake (DMI) and eating rate were increased (p < 0.01; 3.6% and 5.2%, respectively), while feed efficiency decreased (p < 0.05) in CEC compared with CON. Additionally, CEC decreased (p = 0.02) CH4 yield by 16.4% and tended to reduce daily CH4 production (p = 0.09) and CH4 intensity (p = 0.08) by 13.4% and 14.0%, respectively. Supplementing CEC decreased CH4 concentration in vitro and CH4 yield in vivo without negatively impacting performance parameters.