Assessing the effect of interaction between C-reactive protein and gut microbiome on the risks of anxiety and depression

Abstract

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.

Study of gut microbiota alterations in Alzheimer's dementia patients from Kazakhstan

“…There is also an assumption that the development of sporadic AD might be driven by the microbiome-associated peripheral inflammation 45 . Previous studies investigating the links between gut microbiota and low-grade inflammation marker C-reactive protein found Ruminococcaceae, Akkermansia, and Lactobacillales to be associated with the risk of anxiety and depression 46 . In cardiovascular patients, peripheral C-reactive protein was linked to the abundance of Bifidobacterium, Faecalibacterium , Ruminococcus, and Prevotella 47 .…”

Intestinal Flora Composition Determines Microglia Activation and Improves Epileptic Episode Progress

“…16S rDNA sequencing of intestinal microorganisms showed that f_Ruminococcaceae abundance increased most significantly in the immune-tolerant group ( Figure 3E ). This flora is closely related to nervous system diseases, such as Alzheimer’s disease, depression, and stroke ( Chang et al., 2021 ; Chen et al., 2021 ; Cuervo-Zanatta et al., 2021 ). Ruminococcus helps inhibit the translocation of bacterial products (e.g., LPS) into the blood, which may activate the Toll-like receptor 4 (TLR4), stimulate inflammatory responses, and secrete proinflammatory cytokines ( Shi et al., 2006 ; Cani et al., 2007 ).…”

“…Antiepileptic drugs have different activating or inhibitory effects on metabolic enzymes. For example, carbamazepine, oxcarbazepine, and phenytoin can induce CYP3A4 activity ( Ghosh et al., 2018 ; Chen et al., 2021 ; Roberti et al., 2021 ), whereas levetiracetam, phenobarbital, and phenytoin induce P-gp expression ( Jing et al., 2010 ; Moerman et al., 2011 ; Alvariza et al., 2014 ). Follow- up studies can determine whether the metabolism of antiepileptic drugs is related to the expression of CYP3A1 and P-gp in the intestinal tract and whether changes in the intestinal flora of patients with epilepsy have an impact on the expression of CYP3A and P-gp in the intestinal wall and in an epilepsy model.…”

Alterations in the Gut Microbiota and Metabolomics of Seafarers after a Six-Month Sea Voyage

“…Furthermore, Holdemanella may influence brain function and behavior via the microbiota-gut-brain axis. Chen et al reported previously that Holdemanella was related to a risk of anxiety (β = −0.008; P = 4.20 × 10 −3 ) and depression (β = −0.007; P = 1.39 × 10 −2 ) ( 28 ). Scheepers et al investigated the associations between natural compulsive-like behavior in deer mice and alterations in the gut microbiota and found that the prevalence of Holdemanella was associated with obsessive-compulsive disorder, a disease driven by aberrant cognitive processes ( 29 ).…”