Enteric Glia Regulate Paneth Cell Secretion and Gut Microbial Ecology

Concetti Chiave

Enteric glia are necessary for maintaining normal Paneth cell secretory function, which in turn shapes the composition of the gut microbiome.

Sintesi

The study investigated the functional significance of enteric glia, the glial cells of the enteric nervous system, in regulating the intestinal epithelium and gut microbiome.

Key highlights:

• Plp1 was identified as the most broadly expressed marker of mucosal enteric glia in both mice and humans.
• Genetic depletion of Plp1+ enteric glia in mice had minimal effects on the overall intestinal transcriptome and epithelial cell composition.
• However, glial depletion caused specific changes in Paneth cell gene expression, morphology, and secretory function.
• Paneth cells in glial-depleted mice exhibited abnormal, heterogeneous secretory granules and reduced luminal secretion of the antimicrobial peptide lysozyme.
• The altered Paneth cell secretion was associated with changes in gut microbial composition, including reduced abundance of Lactobacillus species and increased Bacteroides.
• These findings establish a novel role for enteric glia in regulating Paneth cell function and shaping the gut microbiome, without broadly impacting other aspects of intestinal epithelial homeostasis.

Statistiche

Paneth cells in glial-depleted mice exhibited abnormal, heterogeneous secretory granules.
Ileal explants from glial-depleted mice secreted less functional lysozyme than controls.
Glial depletion was associated with reduced abundance of Lactobacillus murinus and L. animalis, and increased abundance of Bacteroides acidifaciens in the fecal microbiome.

Citazioni

"Enteric glia do not exert broad effects on the intestinal epithelium but have an essential role in regulating Paneth cell function and gut microbial ecology."
"Morphologic changes in Paneth cells, similar to those we observed in Cre+ mice, have been reported in studies where cholinergic signaling is blocked or vagal innervation to the intestine is severed."
"The similarities between the shifts in microbial composition observed in these constitutive systems of Paneth cell disruption and our model of acute glial depletion support a functional link between the fecal microbial changes in Cre+ mice and reduced LYZ1 secretion."

Approfondimenti chiave tratti da

Enteric glia regulate Paneth cell secretion and intestinal microbial ecology

by Prochera,A.,... alle www.biorxiv.org 04-19-2024

https://www.biorxiv.org/content/10.1101/2024.04.15.589545v1

Domande più approfondite

How might the disruption of enteric glia-Paneth cell interactions contribute to the pathogenesis of intestinal diseases like inflammatory bowel disease?

The disruption of enteric glia-Paneth cell interactions can have significant implications for the pathogenesis of intestinal diseases such as inflammatory bowel disease (IBD). Paneth cells play a crucial role in maintaining gut homeostasis by secreting antimicrobial peptides that regulate the composition of the gut microbiome and provide innate immunity. When enteric glia, which are essential for regulating Paneth cell secretory function, are disrupted, it can lead to dysregulation of antimicrobial peptide secretion. This dysregulation can result in an altered gut microbiome composition, which is a key factor in the development and progression of intestinal diseases like IBD. Changes in the gut microbiome can disrupt the delicate balance between commensal and pathogenic bacteria, leading to inflammation and tissue damage characteristic of IBD. Additionally, impaired Paneth cell function due to disrupted enteric glia-Paneth cell interactions can compromise the host's ability to defend against microbial invasion and maintain intestinal barrier integrity, further exacerbating the inflammatory response seen in IBD.

How might the disruption of enteric glia-Paneth cell interactions contribute to the pathogenesis of intestinal diseases like inflammatory bowel disease?

Enteric glia can utilize various mechanisms beyond cholinergic signaling to regulate Paneth cell secretory function. One potential mechanism is through the modulation of autophagy, a process crucial for Paneth cell secretion. Glial-derived signals could indirectly influence secretory autophagy in Paneth cells, impacting their ability to secrete antimicrobial peptides. Additionally, enteric glia may regulate Paneth cell function through the secretion of neurotrophic factors or other signaling molecules that directly or indirectly modulate the secretory activity of Paneth cells. By influencing the intracellular processes involved in Paneth cell secretion, enteric glia can play a critical role in maintaining gut homeostasis and regulating the gut microbiome.

Could modulating the interactions between enteric glia and Paneth cells serve as a potential therapeutic strategy for manipulating the gut microbiome in the context of health and disease?

Modulating the interactions between enteric glia and Paneth cells could indeed serve as a promising therapeutic strategy for manipulating the gut microbiome in the context of health and disease. By targeting the signaling pathways involved in enteric glia-Paneth cell interactions, it may be possible to enhance Paneth cell secretory function and optimize antimicrobial peptide production. This, in turn, could help maintain a healthy gut microbiome, prevent dysbiosis, and reduce the risk of intestinal diseases such as inflammatory bowel disease. Therapeutic interventions aimed at restoring or enhancing the communication between enteric glia and Paneth cells could offer a novel approach to promoting gut health and mitigating the pathogenesis of various gastrointestinal disorders.