Sex-dependent effects of nicotine on the microbiota and the brain


The effects of nicotine on the intestinal microbiota, bacterial metabolism and the gut-brain axis are thought to be sex-specific, according to American researchers.


For the first time, a study has explored the sex-specific impact of nicotine on the microbiota and neuroactive chemical signals which influences the composition of the microbiota. Intestinal bacteria, gene expression and metabolites were studied in mice (male and female) after receiving nicotine orally for a period of 13 weeks.

Lower weight gain in males

The analysis confirms that nicotine intake modifies the intestinal bacterial community and that this effect is sex-specific: different bacterial components increased or decreased according to sex. A larger decrease in Christensenellaceae was observed in females than in males. This genus is usually enriched in individuals with a low BMI and male mice gained much less weight than the control mice, an effect that was not observed in the females. Hence the interest in examining the bacterial metabolism which is closely linked to energy homeostasis.

A metabolic modification that differs according to sex

Carbohydrate metabolism was impaired in both females and males. But more specifically, the expression of genes involved in acetate synthesis was further increased in males. According to some studies,  increased levels of acetate in the colon can increase its level in the brain and reduce appetite. These results can support what is found in humans and demonstrate that exposure to nicotine elicits different effects depending on sex.

Consequences for metabolites

Amino acids, neurotransmitters and precursors were impaired differently in a sex-dependent manner, as were metabolites that influence neuronal activity. In the females, levels of compounds such as tyrosine or GABA* were increased. This was also observed in males, who however, displayed reduced levels of glycine. These differences in the action of nicotine on neurotransmitters could offer a path to the understanding of sex-specific addiction mechanisms. The action of nicotine on the brain proves more complex than predicted. Furthermore, its action on the intestinal microbiota and the impairment of gene and metabolic functioning are thought to be dependent on the sex of the subject. The authors consider that future research will allow the precise effects of these modifications on hormone homeostasis in the brain and on behavior to be investigated.


* GABA = gamma-aminobutyric acid, the main inhibitory neurotransmitter in the central nervous system



L. Chi et al., « Nicotine Alters the Gut Microbiome and Metabolites of Gut-Brain Interactions in a Sex-Specific Manner », Chem. Res. Toxicol., vol. 30, nᵒ 12, p. 2110‑2119, déc. 2017.