Alterations in Faecal and Serum Metabolic Profiles in Patients with Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (nAMD) is a common and multifactorial disease in the elderly that may lead to irreversible vision loss; yet the pathogenesis of AMD remains unclear. In this study, nontargeted metabolomics profiling using ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry was applied to discover the metabolic feature differences in both faeces and serum samples between Chinese nonobese subjects with and without nAMD. In faecal samples, a total of 18 metabolites were significantly altered in nAMD patients, and metabolic dysregulations were prominently involved in glycerolipid metabolism and nicotinate and nicotinamide metabolism. In serum samples, a total of 29 differential metabolites were founded, involved in caffeine metabolism, biosynthesis of unsaturated fatty acids, and purine metabolism. Two faecal metabolites (palmitoyl ethanolamide and uridine) and three serum metabolites (4-hydroxybenzoic acid, adrenic acid, and palmitic acid) were selected as potential biomarkers for nAMD. Additionally, the significant correlations among dysregulated neuroprotective, antineuroinflammatory, or fatty acid metabolites in faecal and serum and IM dysbiosis were found. This comprehensive metabolomics study of faeces and serum samples showed that alterations in IM-mediated neuroprotective metabolites may be involved in the pathophysiology of AMD, offering IM-based nutritional therapeutic targets for nAMD.

The toxic mechanism of 6:2 Cl-PFESA in adolescent male rats: Endocrine disorders and liver inflammation regulated by the gut microbiota-gut-testis/liver axis.

In previous studies, 6:2 chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), a perfluorooctanesulfonate alternative, has been demonstrated to be toxic to mammals. However, the toxic mechanism of 6:2 Cl-PFESA in mammals is unknown. Herein, adolescent male rats were administered 50 µg/kg/Day 6:2 Cl-PFESA for 28 days (oral gavage) to estimate the toxicity of 6:2 Cl-PFESA and investigate its toxic mechanism. Significant changes in some hematological indicators (e.g., aspartate transaminase and neutrophils) and liver sections (inflammatory cell infiltration) indicated that 6:2 Cl-PFESA exposure caused rat hepatotoxicity. Six steroid hormones (e.g., testosterone, progesterone, and cortisol) in serum and thirteen genes in testicles (related to the pathway of steroid hormone biosynthesis) were significantly regulated in 6:2 Cl-PFESA-treated rats. This suggested that 6:2 Cl-PFESA induced rat endocrine disorders. Compared to the controls, the mean relative abundance of Ruminococcaceae, Pasteurellaceae, Micrococcaceae, and Desulfovibrionaceae was significantly regulated by 1.3-, 0.40-, 0.32-, and 3.2-fold in the 6:2 Cl-PFESA rats, respectively. The 6:2 Cl-PFESA treatment also significantly disturbed 47 gut metabolites (29 upregulated and 18 downregulated), mainly bile acids, short-chain fatty acids, and amino acids. In summary, 6:2 Cl-PFESA induced endocrine disorders and liver inflammation in rats by altering the gut microbiota-gut-testis/liver axis. This study first reveals the toxic mechanism of 6:2 Cl-PFESA in mammals through a multiomics approach and provides comprehensive insight into the toxic mechanism of 6:2 Cl-PFESA.

Multiomics implicate gut microbiota in low cypermethrin (CP) exposure induced multiorgan toxicological effects in pubertal male rats.

Cypermethrin (CP), widely used as a broad-spectrum pesticide, has raised concerns over its frequent presence in the environment and potential health risks. The present study focused on incorporating the gut-organ axis theory to reinterpret the toxicological effects and mechanisms following CP exposure at environmentally relevant concentrations (0.1 mg/kg/d and 0.5 mg/kg/d) in pubertal male rats. The results showed alterations in histopathological and organosomatic indices in the liver, brain, and epididymis. Through multiomics network analysis, it was found that Lachnospiraceae and Ruminococcaceae may contribute to the alteration in serum L-carnitine and trigonelline, leading to hepatic lipid accumulation following CP exposure. Additionally, Ruminococcaceae, Lachnospiraceae, and Porphyromonadaceae were associated with CP-induced glutamatergic hypofunction and overproduction of TNF-α, potentially contributing to the brain neurotoxicity. Overall, the study provides important insights into the potential mechanisms underlying CP-induced toxicity and highlights the need for continued research to fully understand the implications for CP-induced health risks. The incorporation of the gut-organ axis theory in the study provides a promising avenue for future research into the potential interactions between gut microbiota and organ toxicity, and the potential for targeted interventions to mitigate the adverse effects of environmental toxins.