In summary, the midgut acts as an integrator of the nutritional status of the animal, and during unfavorable conditions, it alters the behavioral output from two distinct enteric circuits by modifying an insulin and a non-insulin peptidergic signaling axis.

(18/n)

The midgut epithelium not only signals to the NSM neurons in the foregut, but also to the hindgut enteric neurons using a different neuropeptide, NLP-40, to sustain normal defecation behavior during favorable conditions.

(17/n)

Which neurons in the ENS circuit sense the midgut-derived insulin signals to sustain normal feeding behavior in favorable environments? We found these recipient neurons to be the serotonergic NSM neurons of the foregut ENS circuit.

(16/n)

CRISPR-mediated deletion of ins-7 or ins-35 inhibits foregut contractions in well-fed conditions, while constitutive expression of ins-7 and ins-35 from the midgut is sufficient to induce contractions of the silenced foregut in animals experiencing acute starvation!

(15/n)

So, what are the endogenously released insulin peptides from the midgut epithelium in well-fed conditions? We found two such peptides, ins-7 and ins-35, from a single-cell RNA dataset generated by my friend, Itai Toker.
www.cell.com/current-biol...

(14/n)

Does inhibition of secretion machinery genes affect neuropeptide release from the midgut epithelium during starvation? I tested this using a secretion reporter that allows visualization of the release of an insulin peptide from the midgut into the body cavity (coelom).

(13/n)

Comparing our findings to a previous study, we found that DAF-16/FoxO inhibits the expression of multiple components of the neuropeptide secretion machinery of midgut epithelial cells.

(12/n)

To identify these interorgan signals, we used a transcriptomic approach that used tissue-specific AID2 to identify the DAF-16/FoxO-regulated genes in the midgut epithelium during acute starvation.

(11/n)

We showed that DAF-16/FoxO removal not just from enteric neurons, but also from the midgut (intestinal) epithelium, induced foregut contractions during acute starvation in dauers! This suggested active interorgan communication between these tissues.

(10/n)

Does inhibition of the insulin receptor DAF-2 during starvation inhibit feeding behavior by activating the transcription factor DAF-16/FoxO in enteric neurons? To test this, we removed DAF-16/FoxO from the ENS using the auxin-inducible degron (AID) technology.

(9/n)

We found that inhibiting the insulin receptor (DAF-2) only in the enteric neurons of the animal, using a dominant negative strategy, reduces the rate of feeding even when food is abundant, and mimics the behavioral effects of starvation.

(8/n)

We hypothesized that insulin signaling, which is an evolutionary conserved nutrient sensing pathway, might play in role in altering the output from ENS circuits during starvation.

(7/n)

We found that experiencing short-term starvation during adulthood reduces the rates of feeding and defecation, while acute developmental starvation, which results in entry into the dauer diapause stage, completely shuts down these enteric behaviors.

(6/n)

The C. elegans ENS has two circuits: the PENs in the foregut (pharynx) control feeding behavior, and the HENs in the hindgut control defecation behavior. Both of these enteric behaviors are extremely rhythmic in well-fed conditions.

(5/n)

Viroid-like colonists of human microbiomes

doi.org/10.1016/j.ce...