# Adlercreutzia-modulated polyunsaturated fatty acid metabolism underlies nicotine’s anti-obesity effects

## TL;DR

Nicotine reduces obesity in mice by altering gut bacteria, particularly increasing Adlercreutzia, which helps metabolize fatty acids.

## Contribution

Identifies Adlercreutzia and its role in PUFA metabolism as a novel mechanism for nicotine's anti-obesity effects.

## Key findings

- Chronic low-dose nicotine reduces obesity and related metabolic issues in mice.
- Nicotine's effects depend on gut microbiota, especially the genus Adlercreutzia.
- Adlercreutzia enhances PUFA metabolism, contributing to anti-obesity effects.

## Abstract

The regulatory effects of nicotine on energy balance through central and peripheral mechanisms have been reported. However, its impact on obesity and gut microbiota at safe doses remains unclear.

In this study, it was found that chronic oral nicotine administration daily at relative low dose (0.5 mg/kg) significantly alleviated high-fat diet (HFD)-induced obesity phenotypes in mice, including body weight gain, fat deposits, hepatic steatosis, inflammation and metabolic dysfunction. Gut microbiota depletion and fecal microbiota transplantation (FMT) confirmed that these beneficial effects were microbiota-dependent. Metagenomic sequencing confirmed that nicotine administration reshaped gut microbiota composition, and specifically enriched the commensal genus Adlercreutzia, whose increased abundance correlated with improved biochemical indicators related to obesity. Furthermore, transplantation of Adlercreutzia reproduced anti-obesogenic effects, suggesting it was a key factor for nicotine reducing HFD-induced obesity. Untargeted metabolomics analysis combined association analysis further demonstrated that nicotine modulated host metabolic profiles via gut microbiota-metabolite axis, particularly enhancing Adlercreutzia-linked lipid metabolites involved in polyunsaturated fatty acid (PUFA) metabolism.

Collectively, our study elucidates the critical involvement of gut microbiota in nicotine-induced obesity amelioration, uncovers a novel Adlercreutzia-PUFA metabolic axis mediating nicotine’s anti-obesity effects, and highlight Adlercreutzia potentiation as a promising microbiota-directed invention strategy for obesity and metabolic syndrome.