Assessing the effect of interaction between gut microbiome and inflammatory bowel disease on the risks of depression

Xiaoyue Qin; Chuyu Pan; Qingqing Cai; Yijing Zhao; Dan He; Wenming Wei; Na Zhang; Sirong Shi; Xiaoge Chu; Feng Zhang

doi:10.1016/j.bbih.2022.100557

Assessing the effect of interaction between gut microbiome and inflammatory bowel disease on the risks of depression

Brain Behav Immun Health. 2022 Nov 21:26:100557. doi: 10.1016/j.bbih.2022.100557. eCollection 2022 Dec.

Authors

Xiaoyue Qin¹, Chuyu Pan¹, Qingqing Cai¹, Yijing Zhao¹, Dan He¹, Wenming Wei¹, Na Zhang¹, Sirong Shi¹, Xiaoge Chu¹, Feng Zhang¹

Affiliation

¹ Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

Abstract

Background: Gut microbiome and inflammatory bowel disease (IBD) are implicated in the development of depression, but the effect of their interactions on the risk of depression remains unclear. We aim to analyze the effect of interactions between gut microbiome and IBD on the risk of depression, and explore candidate genes involving the interactions.

Methods: Using the individual genotype and depression traits data from the UK Biobank, we calculated the polygenetic risk scores (PRS) of 114 gut microbiome, ulcerative colitis (UC), Crohn's disease (CD), and total IBD (CD + UC) respectively. The effects of interactions between gut microbiome and IBD on depression were assessed through a linear regression model. Moreover, for observed significant interactions between gut microbiome PRS and IBD PRS, PLINK software was used to test pair-wise single nucleotide polymorphisms (SNPs) interaction of corresponding gut microbiome PRS and IBD PRS on depression.

Results: We found 64 candidate interactions between gut microbiome and IBD on four phenotypes of depression, such as F_Lachnospiraceae (RNT) × (CD + UC) for patient health questionnaire-9 (PHQ-9) score (P = 1.48 × 10^-3), F_Veillonellaceae (HB) × UC for self-reported depression (P = 2.83 × 10^-3) and P_Firmicutes (RNT) × CD for age at first episode of depression (P = 8.50 × 10^-3). We observed interactions of gut-microbiome-associated SNPs × IBD-associated SNPs, such as G_Alloprevotella (HB)-associated rs147650986 (GPM6A) × IBD-associated rs114471990 (QRICH1) (P = 2.26 × 10^-4).

Conclusion: Our results support the effects of interactions between gut microbiome and IBD on depression risk, and reported several novel candidate genes for depression.

Keywords: ASD, Autism spectrum disorders; CD, Crohn's disease; CI, Confidence interval; CNS, Central nervous system; Depression; ENS, Enteric nervous system; ER, Endoplasmic reticulum; FGFP, Flemish gut flora project; GWAS, Genome-wide associations study; Gut microbiome; HB, Hurdle binary; HPA, Hypothalamic-pituitary-adrenal; HRC, Haplotype reference consortium; IBD, Inflammatory bowel disease; Inflammatory bowel disease (IBD); LD, Linkage disequilibrium; PCs, Principal components; PHQ-9, Patient health questionnaire-9; PNT, Rank normal transformed; PRS, Polygenetic risk scores; QC, Quality control; SCFAs, Short-chain fatty acids; SCZ, Schizophrenia; SNPs, Single nucleotide polymorphisms; TDI, Townsend deprivation index; UC, Ulcerative colitis.

Abstract

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