Response of the microbiome–gut–brain axis in Drosophila to amino acid deficit

Boram Kim, Makoto I. Kanai, Yangkyun Oh, Minsoo Kyung, Eun Kyoung Kim, In Hwan Jang, Ji Hoon Lee, Sang Gyu Kim, Greg S.B. Suh, Won Jae Lee

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


A balanced intake of macronutrients—protein, carbohydrate and fat—is essential for the well-being of organisms. An adequate calorific intake but with insufficient protein consumption can lead to several ailments, including kwashiorkor1. Taste receptors (T1R1–T1R3)2 can detect amino acids in the environment, and cellular sensors (Gcn2 and Tor)3 monitor the levels of amino acids in the cell. When deprived of dietary protein, animals select a food source that contains a greater proportion of protein or essential amino acids (EAAs)4. This suggests that food selection is geared towards achieving the target amount of a particular macronutrient with assistance of the EAA-specific hunger-driven response, which is poorly understood. Here we show in Drosophila that a microbiome–gut–brain axis detects a deficit of EAAs and stimulates a compensatory appetite for EAAs. We found that the neuropeptide CNMamide (CNMa)5 was highly induced in enterocytes of the anterior midgut during protein deprivation. Silencing of the CNMa–CNMa receptor axis blocked the EAA-specific hunger-driven response in deprived flies. Furthermore, gnotobiotic flies bearing an EAA-producing symbiotic microbiome exhibited a reduced appetite for EAAs. By contrast, gnotobiotic flies with a mutant microbiome that did not produce leucine or other EAAs showed higher expression of CNMa and a greater compensatory appetite for EAAs. We propose that gut enterocytes sense the levels of diet- and microbiome-derived EAAs and communicate the EAA-deprived condition to the brain through CNMa.

Original languageEnglish
Pages (from-to)570-574
Number of pages5
Issue number7860
StatePublished - 27 May 2021

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© 2021, The Author(s), under exclusive licence to Springer Nature Limited.


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