Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma: a mediation Mendelian randomization study.

OBJECTIVE: This study aims to investigate the causal relationships between specific dietary habits and the risk of gout, while identifying the mediators involved in these associations. METHODS: We initially assessed the causal effects of five dietary habits on gout by two-sample Mendelian randomization (MR). Subsequently, we identified mediators from five plasma metabolites by two-step MR, including urate, urea, sex hormone-binding globulin (SHBG), interleukin-18 (IL-18), and C-reactive protein (CRP). Next, we quantified the proportion of mediation effects by multivariable Mendelian randomization (MVMR). Last, we performed reverse MR analyses. Sensitivity analyses were conducted to enhance the robustness of our findings. RESULTS: Only coffee intake demonstrated a significant negative casual effect on gout (inverse variance weighted: OR = 0.444, p = 0.049). In two-step MR, coffee intake decreased urate and urea while increased SHBG levels, but did not affect IL-18 and CRP levels. Besides, urate and urea showed positive causal effects while SHBG exhibited a negative impact on gout. In mediation analysis, urate, urea, and SHBG respectively mediated 53.60%, 16.43%, and 4.81% of the total causal effect of coffee intake on gout. The three mediators collectively mediated 27.45% of the total effect. Reverse MR analyses suggested no significant reverse causal effects. Sensitivity analyses supported the reliability of our causal inferences. CONCLUSION: Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma. These findings accentuate the benefits of coffee intake for gout management. The mediators may provide a novel insight into potential therapeutic targets for gout prevention. Key Points • This study determines the causally protective effect of coffee intake on gout. • We reveal that coffee intake reduced the risk of gout by decreasing urate and urea while increasing SHBG levels in plasma. • Identifying specific mediators in the causal pathway from coffee intake to gout provides valuable information for clinical interventions of gout.

Mitigation of atrazine-induced oxidative stress on soybean seedlings after co-inoculation with atrazine-degrading bacterium Arthrobacter sp. DNS10 and inorganic phosphorus-solubilizing bacterium Enterobacter sp. P1.

Atrazine toxicity is one of the limiting factors inhibiting sensitive plant growth. Previous studies showed that atrazine-degrading bacteria could alleviate atrazine toxicity. However, there is limited information on how atrazine-degrading bacteria and plant growth-promote bacteria alleviate atrazine toxicity in soybeans. Therefore, the current study aimed to explore the atrazine removal, phosphorus utilization, and the oxidative stress alleviation of atrazine-degrading bacterium Arthrobacter sp. DNS10 and/or inorganic phosphorus-solubilizing bacterium Enterobacter sp. P1 in the reduction of atrazine toxicity in soybean. The results showed that atrazine exposure to soybean seedlings led to significant inhibition in growth, atrazine removal, and phosphorus utilization. However, the co-inoculatied strains significantly increased seedlings biomass, chlorophyll a/b contents, and total phosphorus in leaves accompanied by great reduction of the atrazine-induced antioxidant enzymes activities and malonaldehyde (MDA) contents, as well as atrazine contents in soil and soybeans under atrazine stress. Furthermore, transcriptome analysis highlighted that co-inoculated strains increased the expression levels of genes related to photosynthetic-antenna proteins, carbohydrate metabolism, and fatty acid degradation in leaves. All the results suggest that the co-inoculation mitigates atrazine-induced oxidative stress on soybean by accelerating atrazine removal from soil and phosphorus accumulation in leaves, enhancing the chlorophyll contents, and regulating plant transcriptome. It may be suggested that co-inoculation of atrazine-degrading bacteria and inorganic phosphorus-solubilizing bacteria can be used as a potential method to alleviate atrazine toxicity to the sensitive crops.