# Microbiome Alteration Prevents Abstinence-Induced Nicotine Withdrawal in a Well-Established Planarian Model

## TL;DR

Changing the gut microbiome in planarians reduces nicotine withdrawal symptoms, suggesting diet and microbes may influence addiction.

## Contribution

This study is the first to show that microbiome alteration can reduce nicotine withdrawal in a planarian model.

## Key findings

- Ampicillin pretreatment significantly attenuated nicotine withdrawal-like behavior in planarians.
- Microbiome diversity was reduced by ampicillin and kanamycin, especially decreasing Sphingomonas and Pedobacter bacteria.
- Altering the microbiome may influence susceptibility to substance use disorders.

## Abstract

The prevalence of substance use disorders (SUDs) is unequally distributed across socioeconomic strata. Although several genetic predispositions and psychosocial influences play integral roles, environmental factors are undoubtedly additional contributors. We propose that a potential common factor could be diet. More specifically, circumstances such as economic challenges could lead to limited food choices and poor-quality diets, and this could result in differences in microbiome composition compared to less SUD-susceptible populations having otherwise similar risk factors. The current study investigated the effect of altering the microbiome on drug withdrawal from nicotine using a standard planarian model. Planarians (Girardia dorotocephala) were treated with the broad-spectrum antibiotics ampicillin (a ß-lactam) and kanamycin (a non-ß-lactam), alone and in combination, and microbiomes were analyzed using culture techniques, microscopy, and metagenomic methods. Alphaproteobacteria such as Sphingomonadaceae were detected in the microbiome. Ampicillin or kanamycin reduced the microbiome diversity, notably reducing Sphingomonas and Pedobacter bacteria. One-week treatment with ampicillin and kanamycin did not affect planarian spontaneous locomotor activity. However, pretreatment with ampicillin, but not kanamycin or the combination, significantly attenuated abstinence-induced nicotine withdrawal-like behavior. These results suggest that alteration of the microbiome decreases nicotine withdrawal in this planarian species, and, more broadly, supports the idea that the microbiome might influence the susceptibility and/or maintenance of SUDs.