Dr Alessandro Mineo, postdoc in the LMS Gut Signalling and Metabolism research group recently published an article in Cell Metabolism discussing the interplay between digestive remodelling and immunity. Here in this blog, his explores the connection further and touches upon his own research goals…

The link between nutrient sensing and immunity is conserved across the animal kingdom. To ensure survival, organisms, including humans, rely on deeply conserved signaling pathways that not only sense nutritional and immune challenges, but also ensure coordination of immune and metabolic responses. Such pathways are not hardwired: self-preservation, immunity and reproduction are all energetically costly processes so, when faced with external choices, animals have to make tough choices. They may choose to extend their lifespan at the expense of reproductive capacity, or they may opt to put their offspring at risk in favor of boosting their immunity. How is this decision made?

Flies are no exception to this. Using the sophisticated genetics tools of the fruit fly Drosophila melanogaster, recent work has shown that skeletal muscles are at the hub of this decision. Upon bacterial infection, muscles release glutamate, a common amino acid that can act via a plethora of biological processes to mobilise lipids from the fly adipose tissue to sustain the energetically costly immune defense. They do this at the expenses of their offspring as increased infection resistance causes sterility. Hence, in female flies, infection resistance comes at the cost of reduced fecundity, and muscles are the “control centre” of an energetic tradeoff between immunity and reproduction.

Fascinated by how muscles can signal and influence organismal physiology, I am studying them in the LMS Gut Signalling and Metabolism Group led by Professor Irene Miguel-Aliaga. In particular, I am focusing on an appealing, yet poorly studied, type of muscle: the visceral muscle that ensheath the intestine of fruit flies. These muscles are responsible for peristalsis, the movement of food along the digestive tract, but they can also act to foster intestinal plasticity through promotion of intestinal stem cell proliferation, nutrient absorption and intestinal resizing. Indeed, even in adult animals, the small intestine is a very plastic organ that can remodel to meet the metabolic organismal needs.

This is particularly evident in the context of reproduction. Reproductive needs alter the intestine of females across many animal species, yet the underlying mechanisms and their physiological significance are incompletely understood. Fruit flies are no exception: previous work in the LMS Gut Signalling and Metabolism group has shown that, in female flies, mating increases intestinal stem cell proliferation and dramatically resizes the intestine. All these processes are needed in females to enhance nutrient absorption and meet the needs of reproduction. However, dramatic remodelling of the intestine poses the question of how intestinal remodelling is coordinated between the intestinal epithelium and the visceral muscle layer that surround it. My research is now trying to elucidate how the intestine and the visceral muscles that wrap around it are coordinating to remodel the digestive tract and meet the needs of reproduction. Given the deep conservation of key metabolic signaling pathways, sophisticated genetic tools in the fruit fly can be leveraged to discover novel mechanisms in inter-organ communication and provide valuable insights into the links between metabolic dysregulation and disease in humans.