Causal relationship between gut microbiota and malignant lymphoma: a two-way two-sample mendelian randomization study

Area of Science:

• Microbiome research
• Oncology
• Genetic epidemiology

Background:

• Gut microbiota plays a role in hematologic malignancies, including malignant lymphoma.
• Previous studies have conflicting findings due to confounding factors and reverse causality.
• Mendelian randomization (MR) offers a robust method to infer causality using genetic variants as instrumental variables (IVs).

Purpose of the Study:

• To investigate the bidirectional causal relationships between gut microbiota and malignant lymphoma.
• To address controversies in existing population-based studies on this association.
• To leverage MR to minimize bias and establish causal links.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) analysis.
• Utilized summary-level data from the MiBioGen Consortium (18,340 participants) for gut microbiota.
• Sourced malignant lymphoma data from OpenGWAS (490,803 participants).
• Employed standard quality-controlled single-nucleotide polymorphisms (SNPs) as IVs and various MR statistical methods.
• Conducted reverse MR analysis for identified bacterial taxa.

Main Results:

• Identified seven causal relationships between gut microbiota and malignant lymphoma.
• Specific taxa associated with increased lymphoma risk include *Bacteroidetes*, *Bacilli*, *Rikenellaceae*, *Eubacterium nodatum* group, *Oxalobacter*, *Parabacteroides*, and *Sellimonas*.
• No significant pleiotropy or heterogeneity was detected; no reverse causality was found.

Conclusions:

• Established potential causal links between specific gut microbiota and malignant lymphoma.
• Findings provide a foundation for future research on gut microbiota and lymphoma.
• May aid in developing diagnostic, therapeutic, and preventive strategies for lymphoma.