Alsudayri A. et al., (2024) Gut microbiota regulate maturation and mitochondrial function of nutrient sensing enteroendocrine cells. Development 151(8):dev202544.
https://pubmed.ncbi.nlm.nih.gov/38577841/
https://pubmed.ncbi.nlm.nih.gov/38577841/
|
Enteroendocrine cells (EECs) are crucial for sensing ingested nutrients and regulating feeding behavior. How gut microbiota regulate the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis demonstrates that commensal microbiota colonization significantly increases the expression of many genes associated with mitochondrial function. Using new methods to image EEC cytoplasmic and mitochondrial Ca2+ activity in live zebrafish, our data revealed that it is dynamically regulated during the EEC development process. Mature EECs display an increased mitochondrial-to-cytoplasmic Ca2+ ratio. Mitochondria are evenly distributed in the cytoplasm of immature EECs. As EECs mature, their mitochondria are highly localized at the basal membrane where EEC vesicle secretion occurs. Conventionalized (CV) EECs, but not germ-free (GF) EECs, exhibit spontaneous low-amplitude Ca2+ fluctuation. The mitochondrial-to-cytoplasmic Ca2+ ratio is significantly higher in CV EECs. Nutrient stimulants, such as fatty acid, increase cytoplasmic Ca2+ in a subset of EECs and promote a sustained mitochondrial Ca2+ and ATP increase. However, the nutrient-induced EEC mitochondrial activation is nearly abolished in GF zebrafish. Together, our study reveals that commensal microbiota are crucial in supporting EEC mitochondrial function and maturation.
|
L. Ye, J. F. Rawls. (2021) Microbial influences on gut development and gut-brain communication. Development 148 (21): dev194936.
https://pubmed.ncbi.nlm.nih.gov/34758081/
https://pubmed.ncbi.nlm.nih.gov/34758081/
The developmental programs that build and sustain animal forms also encode the capacity to sense and adapt to the microbial world within which they evolved. This is abundantly apparent in the development of the digestive tract, which typically harbors the densest microbial communities of the body. Here, we review studies in human, mouse, zebrafish and Drosophila that are revealing how the microbiota impacts the development of the gut and its communication with the nervous system, highlighting important implications for human and animal health.
|
L. Ye, et al. (2021) Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways. Cell Host & Microbe. 29(2):179-196.e9.
https://pubmed.ncbi.nlm.nih.gov/33352109/ 
The intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EECs). EECs communicate nutritional information to the nervous system, but whether they also relay signals from intestinal microbes remains unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda activate EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increase intestinal motility. Microbial, pharmacological, or optogenetic activation of Trpa1+EECs directly stimulates vagal sensory ganglia and activates cholinergic enteric neurons by secreting the neurotransmitter 5-hydroxytryptamine (5-HT). A subset of indole derivatives of tryptophan catabolism produced by E. tarda and other gut microbes activates zebrafish EEC Trpa1 signaling. These catabolites also directly stimulate human and mouse Trpa1 and intestinal 5-HT secretion. These results establish a molecular pathway by which EECs regulate enteric and vagal neuronal pathways in response to microbial signals.
|
L. Ye, O. Mueller, J. Bagwell, M. Bagnat, R. A. Liddle, J. F. Rawls. (2019) High fat diet induces microbiota-dependent silencing of enteroendocrine cells. Elife. 8: e48479.
https://elifesciences.org/articles/48479
https://elifesciences.org/articles/48479
Enteroendocrine cells (EECs) are specialized sensory cells in the intestinal epithelium that sense and transduce nutrient information. Consumption of dietary fat contributes to metabolic disorders, but EEC adaptations to high fat feeding were unknown. Here, we established a new experimental system to directly investigate EEC activity in vivo using a zebrafish reporter of EEC calcium signaling. Our results reveal that high fat feeding alters EEC morphology and converts them into a nutrient insensitive state that is coupled to endoplasmic reticulum (ER) stress. We called this novel adaptation 'EEC silencing'. Gnotobiotic studies revealed that germ-free zebrafish are resistant to high fat diet induced EEC silencing. High fat feeding altered gut microbiota composition including enrichment of Acinetobacter bacteria, and we identified an Acinetobacter strain sufficient to induce EEC silencing. These results establish a new mechanism by which dietary fat and gut microbiota modulate EEC nutrient sensing and signaling.
L. Ye, R. A. Liddle. (2017) Gastrointestinal hormones and the gut connectome. Curr Opin Endocrinol Diabetes Obes. 24(1):9-14.
https://pubmed.ncbi.nlm.nih.gov/27820704/
https://pubmed.ncbi.nlm.nih.gov/27820704/
L. Ye, M. A. Robertson, T. L. Mastracci, R. M. Anderson. (2016) An insulin signaling feedback loop regulates pancreas progenitor cell differentiation during islet development and regeneration. Development Biology. 409(2):354-69.
https://pubmed.ncbi.nlm.nih.gov/26658317
https://pubmed.ncbi.nlm.nih.gov/26658317
L. Ye, M. A. Robertson, D. Hesselson, D. Y. Stainier, R. M. Anderson. (2015) Glucagon signaling is enssential for beta cell neogenesis and transdifferentiation from alpha cells in zebrafish. Development. 142:1407-1417.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392596/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392596/