Gut microbiome remodeling provides protection from an environmental toxin.

Gut microbiomes contribute to animal health and fitness. The immense biochemical diversity of bacteria holds particular potential for neutralizing environmental toxins and thus helping hosts deal with new toxic challenges. To explore this potential, we used Caenorhabditis elegans harboring a defined microbiome, and the antibiotic neomycin as a model toxin, differentially affecting microbiome strains, and also toxic to worms. Worms exposed to neomycin showed delayed development and reduced survival but were protected when colonized with neomycin-resistant Stenotrophomonas. 16S rRNA sequencing, bacterial load quantification, genetic manipulation, and behavioral assays showed that protection was linked to enrichment of Stenotrophomonas carrying a neomycin-modifying enzyme. Enrichment was facilitated by altered bacterial competition in the gut, as well as by KGB-1/JNK-dependent behavioral changes. While microbiome remodeling conferred toxin resistance, it was associated with reduced infection resistance and metabolic changes. These findings suggest that microbiome adaptation can help animals cope with stressors but may have long-term consequences that add to effects of direct intoxication.