Hippocampal Crhr1 conditional gene knockout ameliorated the depression-like behavior and pathological damage in male offspring mice caused by chronic stress during pregnancy.

Numerous studies have demonstrated that chronic stress during pregnancy (CSDP) can induce depression and hippocampal damage in offspring. It has also been observed that high levels of corticotropin-releasing hormone (CRH) can damage hippocampal neurons, and intraperitoneal injection of a corticotropin releasing hormone receptor 1 (CRHR1) antagonist decreases depression-like behavior and hippocampal neuronal damage in a mouse depression model. However, whether CSDP causes hippocampal damage and depression in offspring through the interaction of CRH and hippocampal CRHR1 remains unknown and warrants further investigation. Therefore, hippocampal Crhr1 conditional gene knockout mice and C57/BL6J mice were used to study these questions. Depression-related indexs in male offspring mice were examined using the forced swim test (FST), sucrose preference test (SPT), tail suspension test (TST) and open field test (OFT). Serum CRH levels were measured by enzyme-linked immunosorbent assay (ELISA). Golgi-Cox staining was used to examine the morphological changes of hippocampal neuronal dendrites. Neuronal apoptosis in the hippocampal CA3 regions was detected by terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining. The levels of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR) and protein kinase B (AKT) proteins were measured by Western blot analysis. This study showed that CSDP induces depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring mice. Conditional gene knockout of hippocampal Crhr1 in mice reduced CSDP-induced depression-like behavior, hippocampal neuronal dendrite damage and apoptosis in male offspring, and counteracted the CSDP-induced decreased expression of p-Akt and mTOR activity in male offspring hippocampus. These findings demonstrated that CSDP might inhibit the Akt/mTOR pathway by increasing the levels of CRH, leading to increased CRH-mediated activation of hippocampal CRHR1, thereby inducing synaptic impairment and apoptosis in hippocampal neurons, which in turn leads to depression-like behavior in offspring.

The Abnormal Accumulation of Lipopolysaccharide Secreted by Enriched Gram-Negative Bacteria Increases the Risk of Rotavirus Colonization in Young Adults.

Human rotavirus (HRV) is an enteric virus that causes infantile diarrhea. However, the risk factors contributing to HRV colonization in young adults have not been thoroughly investigated. Here, we compared the differences in dietary habits and composition of gut microbiota between asymptomatic HRV-infected young adults and their healthy counterparts and investigated potential risk factors contributing to HRV colonization. Our results indicated that asymptomatic HRV-infected adults had an excessive intake of milk and dairy and high levels of veterinary antibiotics (VAs) and preferred veterinary antibiotic (PVAs) residues in urine samples. Their gut microbiota is characterized by abundant Gram-negative (G-) bacteria and high concentrations of lipopolysaccharide (LPS). Several opportunistic pathogens provide discriminatory power to asymptomatic, HRV-infected adults. Finally, we observed an association between HRV colonization and disrupted gut microbiota caused by the exposure to VAs and PVAs. Our study reveals the traits of disrupted gut microbiota in asymptomatic HRV-infected adults and provides a potential avenue for gut microbiota-based prevention strategies for HRV colonization.

Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn's disease but not Ulcerative Colitis: a prospective cohort study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently recognized as a condition featured with metabolic dysfunctions in liver. It has been supposed that MAFLD might contribute to the development of IBD, but evidence from prospective cohort studies is lacking and inconclusive. METHODS: A total of 221,546 females and 183,867 males from the UK Biobank cohort enrolled in 2006-2010 were included to examine whether MAFLD and liver function markers were related to incident IBD. MAFLD was identified based on hepatic steatosis defined by fatty liver index plus the prevalence of overweight, type 2 diabetes mellitus, or at least two metabolic abnormalities. Biomarker related to liver function (albumin [ALB], alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]; gamma-glutamyl transferase [GGT], total bilirubin [TB], total protein [TP]) was measured using colorimetric or enzymatic assays. The incidence of IBD was ascertained based on primary care and inpatient records. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for the magnitude of their associations. RESULTS: With a mean follow-up of 12.1 years, 2228 incident IBD cases were documented. We identified 150,385 individuals with MAFLD at baseline and 86% participants' circulating liver function markers were within the normal range. Participants with MAFLD were associated with a 12% (HR 1.12, 95% CI 1.03, 1.23, p = 0.012) increased risk of IBD compared with those without MAFLD at baseline; the association was stronger (p-Heterogeneity = 0.006) with Crohn's disease (HR 1.35, 95% CI 1.15, 1.59, p < 0.001) than ulcerative colitis (HR 1.03, 95% CI 0.93, 1.15, p = 0.57). As for the serum liver function markers, the HRs of IBD for per 1-SD increment in ALB, ALP, AST, and TB concentration were 0.86 (95% CI 0.83, 0.90, p < 0.001), 1.18 (95% CI 1.13, 1.24, p < 0.001), 0.95 (95% CI 0.91, 0.99, p = 0.027), 0.92 (95% CI 0.87, 0.96, p < 0.001), respectively. We did not observe significant associations of GGT and TP with IBD. CONCLUSIONS: Individuals with MAFLD were at increased risk of developing IBD, especially CD, but not UC. Circulating levels of liver function biomarkers as the surrogate indicators of MAFLD were also associated with IBD risk.