Artificial Sweeteners and Autoimmune Diseases: Insights From Integrative Bioinformatics and Mendelian Randomization

Area of Science:

• Immunology
• Toxicology
• Nutritional Science

Background:

• Artificial sweeteners (AS) are common food additives with unclear links to autoimmune diseases (ADs).
• Understanding the immunotoxicological effects of AS is crucial for public health.
• Existing research lacks comprehensive mechanistic insights into AS and AD associations.

Purpose of the Study:

• To investigate the association between artificial sweetener exposure and autoimmune diseases.
• To identify potential molecular and gut microbiota-related mechanisms underlying this association.
• To establish a multi-omics framework linking AS to immune dysregulation.

Main Methods:

• Toxicological prediction (ProTox-II), Mendelian randomization (MR) analysis.
• Bioinformatics analyses, including target prediction and functional enrichment.
• Molecular docking and gut microbiota assessment.

Main Results:

• AS showed high predicted immunotoxic potential.
• Artificially sweetened cereal consumption was positively associated with AD risk (OR=1.223, p=0.04).
• Identified 209 AS-related genes involved in apoptosis and immune signaling pathways, with six core targets implicated.
• AS may suppress beneficial gut bacteria like Akkermansia muciniphila, disrupting metabolic and signaling pathways.

Conclusions:

• This study provides a multi-omics framework linking AS exposure to autoimmune dysregulation.
• Identified potential mechanisms include immune pathway disruption and gut microbiota alterations.
• Findings highlight the immunotoxicological effects of AS and their potential role in AD development.