# Causal Effects of Artificially Sweetened Foods on Chronic Pain Mediated by Gut Microbiota: A Mendelian Randomization Study

## TL;DR

This study investigates how artificial sweeteners might cause chronic pain through changes in gut microbiota, using genetic data to support a causal link.

## Contribution

The study identifies specific gut microbiota that mediate the causal relationship between artificial sweetener consumption and chronic pain using Mendelian randomization.

## Key findings

- Genetic predisposition to consuming artificial sweeteners is linked to increased chronic pain risk via gut microbiota.
- Four gut microbiota types mediate the relationship between artificial sweeteners and three chronic pain types.
- Causal relationships between artificial sweeteners, gut microbiota, and chronic pain are supported by sensitivity analyses.

## Abstract

Emerging evidence suggests that both artificially sweetened foods and gut microbiota may contribute to the development and modulation of physical pain. Despite these findings, the potential mediating role of gut microbiota in the causal pathway linking artificial sweetener consumption to chronic pain remains incompletely understood. We utilized Mendelian randomization (MR) to examine the causal relationships between artificially sweetened foods, gut microbiota, and chronic pain. The data included 211 gut microbial taxa, consumption levels of nine artificially sweetened foods, and seven types of chronic pain. The primary statistical method used was inverse variance weighting (IVW). We explored whether gut microbiota mediate the relationship between artificially sweetened foods and chronic pain. We found that genetic predisposition to consuming artificially sweetened foods is associated with an increased risk of chronic pain through different types of gut microbiota. Two‐step MR suggests the mediating effects of four gut microbiota on three chronic pain: head and neck pain, joint pain, and sciatica. These findings could inform interventions and treatments for chronic pain. Artificially sweetened foods and chronic pain have causal relationships, with gut microbiota mediating the pathway from artificially sweetened food to chronic pain.

In this study, we comprehensively explored whether artificial sweetener foods and gut microbiotas significantly impact the development of chronic pain. Initially, we clarified the positive causal relationships between artificial sweetener foods, gut microbiotas, and chronic pain and conducted sensitivity analyses to support our findings.