Enteric glial–mediated enhancement of intestinal barrier integrity is compromised by morphine

Bauman, Brent D.; Meng, Jingjing; Zhang, Lei; Louiselle, Amanda; Zheng, Eugene; Banerjee, Santanu; Roy, Sabita; Segura, Bradley J.

doi:10.1016/j.jss.2017.05.099

Cited by 39 publications

(32 citation statements)

References 21 publications

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“…In agreement with this, PD patients show fecal biomarkers of inflammation as calprotectin and also increased intestinal permeability as alpha-1-antitrypsin [134]. It is known that the IEB is strongly regulated by EGCs [37][38][39]. Since EGCs is sensitized in PD patients and modulates all these processes, it is speculated that IEB could be impaired by altered glial signaling which could contribute to the inflammatory process.…”

Section: Parkinson's Diseasesupporting

confidence: 53%

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The Enteric Glial Network Acts in the Maintenance of Intestinal Homeostasis and in Intestinal Disorders

Coelho-Aguiar¹,

Veríssimo²,

Costa³

et al. 2020

Glia in Health and Disease

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The enteric nervous system (ENS), also known as second brain, innervates our gastrointestinal tract controlling its functions, such as motility, fluid secretion, nutrient absorption, and even involvement in the control of immunity and inflammatory processes. In the gut, the gliocytes are known as enteric glial cells (EGCs). Enteric glial cells form a network that permeates the entire gut. Enteric glia express the cell surface hemichannel of connexin-43 (Cx43) necessary for the propagation of Ca2 + responses, necessary to maintain their functions. In this chapter, besides the development of ENS and its glial cells and the similarities with the astrocytes in the central nervous system, we approached the important role of the glial network in the control of gut homeostasis, in the interaction with the immune system, and its participation in pathological conditions. EGCs are even capable of replacing lost neurons. Thus the enteric glia is a multifunctional cell, which through its multiple interactions maintains the integrity of the ENS allowing it to be resistant to the different and constant aggressions suffered by the digestive system.

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Section: Parkinson's Diseasesupporting

confidence: 53%

“…GDNF also inhibits apoptosis of EGCs in an autocrine manner [34]. Mu opioid receptor activation by morphine in EGCs decreases their GDNF synthesis, with consequent IEB disruption [39]. Moreover, GDNF has been shown to increase the integrity of the IEB via ZO-1 upregulation [38].…”

Section: Functions Of Egcs In Gut Homeostasis: Released Factors By Egmentioning

confidence: 99%

The Enteric Glial Network Acts in the Maintenance of Intestinal Homeostasis and in Intestinal Disorders

Coelho-Aguiar¹,

Veríssimo²,

Costa³

et al. 2020

Glia in Health and Disease

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“…The EGC‐epithelial cell unit has also been associated with the anti‐inflammatory modulation of the immune system because EGC‐derived mediators such as GDNF, GSNO ( S ‐Nitrosoglutathione), and 15d‐PGJ2 (15‐Deoxy‐Delta‐12,14‐prostaglandin J2) support an intact epithelial barrier (Bach‐Ngohou et al, ; Neunlist et al, ; Neunlist et al, ; Pochard et al, ; Savidge et al, ), that in turn can dampen inflammation. A recent study of Baumann et al showed a reduced GDNF expression in EGCs in vitro after morphine treatment suggesting a role of EGCs in morphine associated sepsis (Bauman et al, ). As a consequence, a reduced transepithelial resistance in rat intestinal epithelial cells exposed to the supernatants of morphine‐treated EGCs compared to controls was detected.…”

Section: Introductionmentioning

confidence: 99%

Enteric Glia: S100, GFAP, and Beyond

Grundmann

Loris

Maas-Omlor

et al. 2019

The Anatomical Record

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Since several years, the enteric nervous system (ENS) is getting more and more in the focus of gastrointestinal research. While the main interest was credited for years to the enteric neurons and their functional properties, less attention has been paid on the enteric glial cells (EGCs). Although the similarity of EGCs to central nervous system (CNS) astrocytes has been demonstrated a long time ago, EGCs were investigated in more detail only recently. Similar to the CNS, there is not "the" EGC, but also a broad range of diversity. Based on morphology and protein expression, such as glial fibrillary acidic protein (GFAP), S100, or Proteolipid-protein-1 (PLP1), several distinct glial types can be differentiated. Their heterogeneity in morphology, localization, and transcription as well as interaction with surrounding cells indicate versatile functional properties of these cells for gut function in health and disease. Although NG2 is found in a subset of CNS glial cells, it did not colocalize with the glial marker S100 or GFAP in the ENS. Instead, it in part colocalize with PDGFRα, as it does in the CNS, which do stain fibroblast-like cells in the gastrointestinal tract. Moreover, there seem to be species dependent differences. While GFAP is always found in the rodent ENS, this is completely different for the human gut.Only the compromised human ENS shows a significant amount of GFAPpositive glial cells. So, in general we can conclude that the EGC population is species specific and as complex as CNS glia. Anat Rec, 302:1333Rec, 302: -1344Rec, 302: , 2019.

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“…Specifically, many predominant microbes in older animals correlate with CRP and neopterin, which again are generally markers of systemic immune activation and inflammation. It’s known that with age the permeability of the gut increases, allowing more bacterial products to translocate to the blood and promote inflammation (2, 11, 12, 30). Different bacterial products from different microbes could elicit stronger inflammatory responses in the blood, feeding back onto the gut to promote gut permeability.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, inflammatory cytokines in circulation increase with age, leading to chronic systemic inflammation that negatively affects the host’s ability to mount immune responses (1, 9, 10). Age-associated chronic inflammation also negatively affects organ function, such as in the gut where inflammation leads to increased gut permeability, or “leaky” gut (2, 11, 12).…”

Section: Introductionmentioning

confidence: 99%

Age associated microbiome modulation and its association with systemic inflammation in a Rhesus Macaque Model

Pallikkuth

Russell

Sirupangi

et al. 2019

Preprint

Self Cite

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Words)Background: As the individual ages, the immune system decreases in activity while chronic systemic inflammation increases. The microbiome is also affected by age, decreasing in beneficial microbes while increasing in pathogenic, inflammation inducing microbes. While aging is known to affect both, links between the two have been hard to uncover.Methods: Four young (age 3-6 years) and 12 old (age>18 years) Rhesus macaques were recruited for the study. PBMCs and plasma were collected to investigate immune cell subsets by flow cytometry and plasma cytokines by bead based multiplex cytokine analysis respectively. Stool samples were collected by ileal loop for microbiome analysis by shotgun metagenomics and serum, gut microbial lysate and microbe-free fecal extract was used to determine metabolomics by mass-spectrometry.Results: Our aging NHP model recaptured many of the features of the age-associated immune alterations, with increased inflammation and alterations in immune cells subsets with lower number of CD4 T cells and a trend of age associated alterations in maturation subsets in older animals with lower naïve and higher central memory CD4 T cells. Older animals showed a significantly different microbiome from young animals with lower abundance of Firmicutes and higher Archaeal and Proteobacterial species. Correlation analysis showed a link between microbes in older animals with systemic inflammation. Analysis of metabolites in the serum and feces showed significant differences between specific metabolites between young and older animals that can influence age-associated morbidities.Conclusion: These data support the age associated alterations in microbiome profile and its association with persistent systemic inflammation and metabolome changes. Further mechanistic studies are needed to understand the relationship between inflammation and microbiome.Nevertheless, this NHP model recapitulates human age associated changes in immune, inflammatory and microbiome profiles and can be useful for designing future studies targeting microbiome modulations in aging.

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Enteric glial–mediated enhancement of intestinal barrier integrity is compromised by morphine

Cited by 39 publications

References 21 publications

The Enteric Glial Network Acts in the Maintenance of Intestinal Homeostasis and in Intestinal Disorders

The Enteric Glial Network Acts in the Maintenance of Intestinal Homeostasis and in Intestinal Disorders

Enteric Glia: S100, GFAP, and Beyond

Age associated microbiome modulation and its association with systemic inflammation in a Rhesus Macaque Model

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