Immune cell signatures and causal association with irritable bowel syndrome: A mendelian randomization study

Abstract

BACKGROUND

The mucosal barrier's immune-brain interactions, pivotal for neural development and function, are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome (IBS). Prior studies linking immune inflammation with IBS have been inconsistent. To further elucidate this relationship, we conducted a Mendelian randomization (MR) analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS. Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.

AIM

To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS. We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.

METHODS

We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS. By utilizing genetic data from public databases, we examined the causal associations between 731 immune cell markers, encompassing median fluorescence intensity, relative cell abundance, absolute cell count, and morphological parameters, with IBS susceptibility. Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.

RESULTS

Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes. However, our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes (P < 0.05). Nine immune phenotypes demonstrated a protective effect against IBS [inverse variance weighting (IVW) < 0.05, odd ratio (OR) < 1], while 21 others were associated with an increased risk of IBS onset (IVW ≥ 0.05, OR ≥ 1).

CONCLUSION

Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS, providing valuable insights into the pathophysiology of the condition. These results pave the way for the development of more precise biomarkers and targeted therapies for IBS. Furthermore, this research enriches our comprehension of immune cell roles in IBS pathogenesis, offering a foundation for more effective, personalized treatment approaches. These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.

Keywords: Irritable bowel syndrome; Immunophenotypes; Causality; Brain-gut axis; Mendelian randomization; Sensitivity analysis

Core Tip: Our investigation has uncovered a substantial genetic link between immune cell phenotypes and irritable bowel syndrome (IBS), offering critical insights into the disease's pathophysiological underpinnings. This finding is pivotal for advancing our comprehension of IBS and paves the way for innovative diagnostic and therapeutic strategies. Moreover, this knowledge contributes to the development of more precise biomarkers and treatment modalities tailored to IBS, potentially leading to more efficacious personalized care plans for patients. These advancements are anticipated to enhance the quality of life for individuals suffering from IBS and alleviate the disease's burden on patients and their families.