Metabolic regulation of behavior by the intestinal enzyme FMO-2

TL;DR

A gut enzyme in worms affects behavior by changing how tryptophan is processed, linking metabolism to health and lifespan.

Contribution

The study reveals a novel mechanism where the enzyme FMO-2 modulates behavior through tryptophan metabolism in a cell nonautonomous manner.

Findings

Modified fmo-2 expression alters sensory perception and decision-making in C. elegans.

FMO-2 interacts with serotonin and quinolinic acid, derived from tryptophan, to influence behavior.

Gut metabolism communicates satiety and depressive signals via amino acid modification.

Abstract

Many elements of an organism’s behavior are intertwined with the organism’s health. Over a long period of time, health status is also indicative of life span, with improved health correlating with a longer life. However, the relationship between longevity and behavior remains relatively unexplored. Here, we report that modification of a single longevity gene downstream of dietary restriction and hypoxia markedly alters behavior in Caenorhabditis elegans. We found that modified expression of flavin-containing monooxygenase (fmo-2) leads to altered sensory perception and decision-making in a variety of behavioral paradigms. This cell nonautonomous signaling pathway is linked to changes in tryptophan metabolism, where loss of fmo-2 requires the tryptophan metabolite serotonin and overexpressed fmo-2 requires the tryptophan metabolite quinolinic acid to change behavior. These results suggest a unique mechanism for gut metabolism to communicate positive satiety signals and negative depressive signals to the organism by modifying an essential amino acid. They also demonstrate the importance of examining pleiotropic effects in promising longevity interventions.

The intestinal pro-longevity enzyme fmo-2 interacts with tryptophan-derived neuromodulators to change behavior.

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