Peroxisome deficiency or functional impairments directly due to defective peroxisome formation result in devastating genetic conditions known as the peroxisome biogenesis disorders (PBDs) ( Waterham et al., 2016) contribute to the pathology of Alzheimer’s and Parkinson’s diseases, aging, cancer, diabetes, and heart failure and affect immunity ( Dixit et al., 2010 Beach et al., 2012 Fransen et al., 2012 Colasante et al., 2015 Di Cara et al., 2017). Peroxisomes perform many important metabolic functions and maintain cellular redox homeostasis ( Wanders and Waterham, 2006 Nguyen et al., 2008). Peroxin ( Pex) genes encode proteins called peroxins that are required for peroxisome formation and maintenance of peroxisome populations ( Smith and Aitchison, 2013). Peroxisomes are ubiquitous organelles conserved across the breadth of eukaryotes. Understanding how enteric health is maintained therefore has important implications for overall human health and requires knowledge of the signaling pathways that control gut metabolism, stress response, and interactions with microbes.
The intestinal epithelium absorbs nutrients, maintains energy homeostasis, and manages interactions with microorganisms to provide resistance to pathogens and to promote beneficial contacts with commensals ( Clemente et al., 2012 Hooper et al., 2012 Nicholson et al., 2012 Lemaitre and Miguel-Aliaga, 2013 Guo et al., 2014). Peroxisomes in the gut effectively function as hubs that coordinate responses from stress, metabolic, and immune signaling pathways to maintain enteric health and the functionality of the gut–microbe interface. Dysfunctional peroxisomes in gut epithelial cells activate Tor kinase-dependent autophagy that increases cell death and epithelial instability, which ultimately alter the composition of the intestinal microbiota, compromise immune pathways in the gut in response to infection, and affect organismal survival. We report that peroxisomes, organelles involved in lipid metabolism and redox balance, are required to maintain gut epithelium homeostasis and renewal in Drosophila and for survival and development of the organism. Gut homeostasis is necessary for organismal health and changes to the gut are associated with conditions like obesity and diabetes and inflammatory illnesses like Crohn’s disease. The gut has a central role in digestion and nutrient absorption, but it also serves in defending against pathogens, engages in mutually beneficial interactions with commensals, and is a major source of endocrine signals.
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