Qiqihar Medical University

Glyphosate (GLP) is one of the most widely used herbicides in the world. However, its underlying effects on the liver remain unclear. This study aims to investigate the toxic effects and the gut microbiome– and serum metabolite–related mechanisms of GLP on the liver in mice.

16S rDNA sequencing and UPLC-Q-TOF-MS/MS were used to investigate the mechanisms of GLP toxicity in mice administered with 0, 50, 250 and 500 mg/kg/day GLP for 30 days.

GLP induced hepatocyte edema and ballooning as well as inflammatory cell infiltration. Exposure to GLP resulted in increased levels of serum ALT, TBIL, DBIL, and GLU. Microbiota analysis at the phylum level demonstrated that the proportions of Patescibacteria decreased in the GLP-treated group. The genus-level analysis identified 11 different genera, with eight decreased and three increased in the GLP-exposed group. Metabolomics analysis of serum showed 42 differential metabolites between the GLP and control groups. The metabolic pathway enrichment analysis revealed that the pentose phosphate pathway (PPP) and pyrimidine metabolism were significantly activated. Spearman analysis showed that the changes in the differential metabolites of the PPP and pyrimidine metabolism and gut microbiota were strongly associated with the biochemical index.

In conclusion, GLP exposure induces hepatic injury through alterations in the gut microbiome and metabolic pathways, particularly by activating the pentose phosphate pathway and pyrimidine metabolism.

Alcohol dependence (AD) is a global public health concern with strong genetic characteristics. The purpose of this study was to explore the underlying pathogenic genes and mechanisms associated with AD.

This study employed a multi-omics Mendelian randomization approach to identify potential disease-causing genes for AD. Specifically, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomization (SMR) to pinpoint candidate genes associated with AD. Additionally, mediating Mendelian randomization was utilized to investigate the mediating role of the gut microbiota in the relationship between immune cell phenotypes and AD.

Two susceptibility genes associated with AD, ADH1C and POLI, were identified a joint analysis of SMR and integrated cross-tissue and single tissue TWAS in European population. A new genetic locus associated with AD, rs62307318, was uncovered through cross-organism TWAS. This finding was further validated using Mendelian randomization and Phenome-wide association analysis. Additionally, Mendelian randomization identified Paceibacteria as a possible mediator between Myeloid DC AC and AD.

This study identified two genes closely related to AD and explored the possible pathogenesis of AD, which provides a new insight into the treatment and pathogenesis of AD.

Sleep deprivation (SD) is a significant public health concern and a risk factor for neuropsychiatric disorders, including depression. SD disrupts the gut-brain axis, causing dysbiosis and neuroinflammation. Astragalus membranaceus (AST) exhibits antidepressant and anti-inflammatory properties, including modulation of the gut microbiota; however, its neuroprotective effects on SD-induced neuropsychiatric disturbances remain largely unexplored. This study investigates the potential of AST using an innovative integrative multiomics approach.

This study was conducted to investigate the neuroprotective effects of AST against SD-induced depression-like behavior and to explore the mechanism underlying its regulatory effects on the gut-brain axis.

We established a chronic SD mouse model that was subjected to AST intervention and employed a pioneering integrative multiomics approach-combining resting-state functional magnetic resonance imaging for brain function, metagenomics for microbiota profiling, metabolomics for metabolic alterations, and transcriptomics for gene expression in key brain regions. Behavioral tests and cytokine assays complemented these analyses to comprehensively evaluate the therapeutic effects of AST.

SD induced depression-like behavior, neuroinflammation (IL-1β, IL-6, and TNF-α secretion), gut dysbiosis (Proteobacteria expansion, loss of beneficial microbes), and disrupted metabolic pathways. AST alleviated behavioral deficits, normalized brain connectivity, and reduced the levels of proinflammatory cytokines. It also reshaped microbiota, enriching Muribaculum and Butyricicoccus, and restored metabolic profiles, increasing the levels of short-chain fatty acids and promoting bile acid pathways. Integrated analysis linked microbiota restoration to reduced neuroinflammation and improved neuroprotection.

AST modulates the gut-brain axis to counteract SD-induced dysbiosis, neuroinflammation, and metabolic imbalance, alleviating depression-like symptoms. These findings offer novel mechanistic insights into the therapeutic potential of AST for SD-related neuropsychiatric conditions.