Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3321 independent single nucleotide polymorphism (SNP) loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113,693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114,219). At last, 11 candidate CRP × gut microbiome interaction with suggestive significance was detected for PHQ-9 score, such as F_Ruminococcaceae (β = − 0.009, P = 2.2 × 10–3), G_Akkermansia (β = − 0.008, P = 7.60 × 10–3), F_Acidaminococcaceae (β = 0.008, P = 1.22 × 10–2), G_Holdemanella (β = − 0.007, P = 1.39 × 10–2) and O_Lactobacillales (β = 0.006, P = 1.79× 10–2). 16 candidate CRP × gut microbiome interaction with suggestive significance was detected for GAD-7 score, such as O_Bacteroidales (β = 0.010, P = 4.00× 10–4), O_Selenomonadales (β = − 0.010, P = 1.20 × 10–3), O_Clostridiales (β = 0.009, P = 2.70 × 10–3) and G_Holdemanella (β = − 0.008, P = 4.20 × 10–3). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiomes for them.

中文翻译：

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评估 C 反应蛋白和肠道微生物组之间的相互作用对焦虑和抑郁风险的影响

累积证据表明，肠道微生物组可以通过炎症过程影响大脑功能和行为。然而，肠道菌群失调与 C 反应蛋白 (CRP) 相互作用在焦虑和抑郁发展中的作用仍有待阐明。在这项研究中，共有 3321 个与肠道微生物组相关的独立单核苷酸多态性 (SNP) 基因座来自全基因组关联研究 (GWAS)。使用来自英国生物银行的个体水平基因型数据，我们计算了 114 种肠道微生物组相关性状的多基因风险评分 (PRS)。此外，进行回归分析以评估肠道微生物组和 CRP 之间相互作用对患者健康问卷 9 (PHQ-9) (N = 113,693) 和广泛性焦虑症 (GAD-7) (N) 风险的可能影响= 114,219)。最后，PHQ-9 评分检测到 11 个候选 CRP × 肠道微生物组相互作用，具有提示意义，例如 F_Ruminococcaceae (β = - 0.009, P = 2.2 × 10-3), G_Akkermansia (β = - 0.008, P = 7.60 × 10-3) )、F_Acidaminococcaceae (β = 0.008, P = 1.22 × 10-2)、G_Holdemanella (β = - 0.007, P = 1.39 × 10-2) 和 O_Lactobacillales (β = 0.006, P = 1.79× 10-2)。对于 GAD-7 评分，检测到 16 个候选 CRP × 肠道微生物组相互作用具有暗示意义，例如 O_Bacteroidales (β = 0.010, P = 4.00×10-4), O_Selenomonadales (β = − 0.010, P = 1.20 × 10-3) , O_Clostridiales (β = 0.009, P = 2.70 × 10-3) 和 G_Holdemanella (β = - 0.008, P = 4.20 × 10-3)。我们的结果支持 CRP 和肠道微生物组之间的相互作用对焦虑和抑郁风险的显着影响，并为它们确定了几个候选肠道微生物组。