Research Article: The DH31/CGRP enteroendocrine peptide triggers intestinal contractions favoring the elimination of opportunistic bacteria

Date Published: September 4, 2018

Publisher: Public Library of Science

Author(s): Olivia Benguettat, Rouba Jneid, Julie Soltys, Rihab Loudhaief, Alexandra Brun-Barale, Dani Osman, Armel Gallet, Karel Talavera.


The digestive tract is the first organ affected by the ingestion of foodborne bacteria. While commensal bacteria become resident, opportunistic or virulent bacteria are eliminated from the gut by the local innate immune system. Here we characterize a new mechanism of defense, independent of the immune system, in Drosophila melanogaster. We observed strong contractions of longitudinal visceral muscle fibers for the first 2 hours following bacterial ingestion. We showed that these visceral muscle contractions are induced by immune reactive oxygen species (ROS) that accumulate in the lumen and depend on the ROS-sensing TRPA1 receptor. We then demonstrate that both ROS and TRPA1 are required in a subset of anterior enteroendocrine cells for the release of the DH31 neuropeptide which activates its receptor in the neighboring visceral muscles. The resulting contractions of the visceral muscles favors quick expulsion of the bacteria, limiting their presence in the gut. Our results unveil a precocious mechanism of defense against ingested opportunistic bacteria, whether they are Gram-positive like Bacillus thuringiensis or Gram-negative like Erwinia carotovora carotovora. Finally, we found that the human homolog of DH31, CGRP, has a conserved function in Drosophila.

Partial Text

The intestinal mucosa is endowed with several systems of defense to fight against the bacteria that are swallowed along with food. First of all, the gut epithelium is a sealed barrier preventing aggressors from crossing the epithelial layer [1]. Secondly, the gut lining is covered by mucus in vertebrates [2] or a peritrophic membrane in arthropods, which protects it from aggression [3, 4]. Furthermore the innate immune system produces reactive oxygen species (ROS) [5] and antimicrobial peptides (AMPs) to kill bacteria [6, 7]. Finally, the gut epithelium accelerates its cellular renewal to quickly replace damaged cells [8].

In this study, we identified a new physiological circuit that is implicated in the local gut defense and participates in the elimination of ingested allochthonous bacteria (Fig 7F). We demonstrated that the production of immune ROS in response to the presence of allochthonous bacteria in the gut lumen leads to rapid and strong visceral contractions scattered along the midgut, which are involved in the elimination of the ingested bacteria. Most importantly, this quick and efficient response is enabled by a subset of anterior EECs that transmit the signal from the lumen to the visceral mesoderm by releasing DH31, a neuropeptide that presents a conserved function with CGRP in mammals (Fig 7F). This work reinforces the importance of EECs in the defense mechanisms of the gut, beyond the recent discovery of their involvement in innate immune response [38, 45, 51, 52] and in addition to their well-known functions in regulating feeding behavior and digestive physiology [30].