Multiscale analysis reveals that diet-dependent midgut plasticity emerges from alterations in both stem cell niche coupling and enterocyte size

Abstract

The gut is the primary interface between an animal and food, but how it adapts to qualitative dietary variation is poorly defined. We find that the Drosophila midgut plastically resizes following changes in dietary composition. A panel of nutrients collectively promote gut growth, which sugar opposes. Diet influences absolute and relative levels of enterocyte loss and stem cell proliferation, which together determine cell numbers. Diet also influences enterocyte size. A high sugar diet inhibits translation and uncouples ISC proliferation from expression of niche-derived signals but, surprisingly, rescuing these effects genetically was not sufficient to modify diet's impact on midgut size. However, when stem cell proliferation was deficient, diet's impact on enterocyte size was enhanced, and reducing enterocyte-autonomous TOR signaling was sufficient to attenuate diet-dependent midgut resizing. These data clarify the complex relationships between nutrition, epithelial dynamics, and cell size, and reveal a new mode of plastic, diet-dependent organ resizing.

Mechanisms of damage prevention, signalling, and repair impact disease tolerance

“…The remodelling of the gut might be one of the possible driving factors for dimorphism in gut immunity, since males and females differ in their nutritional needs [61]. Studies using Drosophila have shown that males and females can make different diet or nutritional choices in accordance with their reproduction role and demand [63] and the Drosophila midgut plastically resizes in response to changes in dietary sugar and yeast [64]. Whether gut remodelling and nutritional choice-demand causes sex-differences in damage repair process during disease tolerance remains a question for future research.…”

The amino acid transporter CG1139 is required for retrograde transport and fast recovery of gut enterocytes after Serratia marcescens intestinal infection

“…Ever since the discovery of intestinal stem cells in Drosophila (Micchelli & Perrimon, 2006;Ohlstein & Spradling, 2006) and the interest in intestinal infections (Liehl, Blight, Vodovar, Boccard, & Lemaitre, 2006;Nehme et al, 2007;Ji-Hwan Ryu et al, 2006), there has been a renewed interest in studying the homeostasis of the intestinal epithelium in normal and pathogenic conditions (Nicolas Buchon, Silverman, & Cherry, 2014;Lemaitre & Miguel-Aliaga, 2012;De Navascués et al 2012;O'Brien et al, 2011). A recent study underlined the importance of the diet in determining the size of the Drosophila gut and emphasized that the adaptation to novel environmental conditions involves not only the proliferation of ISCs but also on enterocyte growth (Bonfini et al, 2021). As TOR signaling contributes to this adaptation, enterocyte growth is implicitly thought to be a cell-autonomous event.…”

Cellular mechanisms underlying adult tissue plasticity in Drosophila

“…Nutrient-absorptive ECs respond to nutrient environments, and thus the ploidy of ECs can contribute to the size regulation of the adult midgut. In contrast to the regeneration-associated polyploidization regulated by EGFR signalling, nutrient-rich diets promote the polyploidization of ECs via insulin-TOR signalling [ 79 , 97 ]. Given that insulin-TOR signalling also regulates ISC proliferation [ 23 , 85 , 90 , 98 ], one question is to what extent each cellular process contributes to midgut resizing.…”

“…Given that insulin-TOR signalling also regulates ISC proliferation [ 23 , 85 , 90 , 98 ], one question is to what extent each cellular process contributes to midgut resizing. Bonfini et al, have addressed this question using two types of isocaloric diet: one high sugar diet, the other high in yeast (yeast being the primary source of protein and lipids in conventional fly food) [ 97 ]. They found that shifting from the high sugar diet to the high yeast diet promotes ISC proliferation, polyploidization in ECs, and the growth of the adult midgut.…”

“…They found that shifting from the high sugar diet to the high yeast diet promotes ISC proliferation, polyploidization in ECs, and the growth of the adult midgut. Unexpectedly, inhibition of ISC proliferation does not suppress midgut adaptive growth because of the augmented enlargement of ECs, which is mediated by TOR signalling-dependent polyploidization [ 97 ]. These results raise the possibility that the adult midgut senses the dysfunction of ISCs through mechanical tension and/or unknown cellular communication mechanisms to induce compensatory polyploidization of ECs.…”