The Role of the Gut Microbiome in Nicotine Withdrawal and Dependence

Mar 24, 2026Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

The Gut Microbiome's Role in Nicotine Withdrawal and Addiction

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Abstract

Fecal transplants reduced the number of somatic signs and anxiety-like behaviors in nicotine-treated mice up to one week after minipump removal.

Nicotine exposure may alter the gut microbiome, leading to increased permeability and impaired immune responses in the gastrointestinal tract.
Homologous fecal material transplants were used to modify the gut microbiome in a mouse model of nicotine dependence.
Changes in the gut microbiome were observed, with significant shifts in species composition following nicotine treatment and fecal transplants.
The reduction in withdrawal symptoms suggests that gut-brain interactions may play a role in nicotine dependence.

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INTRODUCTION: Smoking is considered a global pandemic with more than 1.3 billion people being active smokers. Increasing evidence suggests that nicotine exposure can lead to changes in the gut microbiome, increases in permeability, and impaired mucosal immune responses in the gastrointestinal tract. However, the literature on behavioral aspects of nicotine-microbiome interaction, such as dependence and withdrawal, is limited. In this study, we used homologous fecal material transplants (FMT) to modify the gut microbiome and its impact on the intensity of nicotine withdrawal in mice.

METHODS: We used osmotic minipumps as an application of chronic nicotine for 15 days and orally gavaged FMT 2x a day to the mice. We assessed the nicotine withdrawal by measuring the number of somatic signs and anxiety-like behaviors at 24 h and 1 week after the mini pump removal. Fecal samples were also collected points to identify the gut microbiome changes.

RESULTS: Fecal transplants reduced the number of somatic signs and anxiety-like behaviors in nicotine-treated mice up to a week after the removal of minipumps. The shotgun metagenomic results of the fecal samples from 24 h after minipumps removal time point show altered gut microbiome with a significant shift in the species composition between the nicotine treated and its homologous FMT treatment.

CONCLUSIONS: Our results indicate that under our experimental conditions fecal transplant can reduce the severity of nicotine withdrawal. This suggests that interactions along the gut-brain axis are important for the development of nicotine dependence and might help lower the risk of cancer and other serious health problems in humans.

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The Role of the Gut Microbiome in Nicotine Withdrawal and Dependence

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