Paneth cells: the hub for sensing and regulating intestinal flora

Zhang, Zheng; Liu, Zhihua

doi:10.1007/s11427-016-5018-5

Cited by 22 publications

(15 citation statements)

References 38 publications

(48 reference statements)

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“…Paneth cells are highly specialized epithelial cells located at the base of the crypts of Lieberkühn of the small intestine. Paneth cells secrete antimicrobial peptides into the crypt lumen, which protect the host from enteric pathogens, help to shape the composition of the colonizing bacteria, safeguard against bacterial translocation across the epithelium, and act as immune modulators and trophic factors ( 24 – 26 ). On the other hand, Paneth cell dysfunction has been associated with gut bacterial changes in obese individuals ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by high-fat feeding

Zhou

Gillilland

et al. 2020

JCI Insight

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High-fat feeding (HFF) leads to gut dysbiosis through unclear mechanisms. We hypothesize that bile acids secreted in response to high-fat diets (HFDs) may act on intestinal Paneth cells, leading to gut dysbiosis. We found that HFF resulted in widespread taxonomic shifts in the bacteria of the ileal mucosa, characterized by depletion of Lactobacillus and enrichment of Akkermansia muciniphila , Clostridium XIVa, Ruminococcaceae, and Lachnospiraceae, which were prevented by the bile acid binder cholestyramine. Immunohistochemistry and in situ hybridization studies showed that G protein–coupled bile acid receptor (TGR5) expressed in Paneth cells was upregulated in the rats fed HFD or normal chow supplemented with cholic acid. This was accompanied by decreased lysozyme + Paneth cells and α-defensin 5 and 6 and increased expression of XBP-1 . Pretreatment with ER stress inhibitor 4PBA or with cholestyramine prevented these changes. Ileal explants incubated with deoxycholic acid or cholic acid caused a decrease in α-defensin 5 and 6 and an increase in XBP-1 , which was prevented by TGR5 antibody or 4PBA. In conclusion, this is the first demonstration to our knowledge that TGR5 is expressed in Paneth cells. HFF resulted in increased bile acid secretion and upregulation of TGR5 expression in Paneth cells. Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by HFF.

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Section: Introductionmentioning

confidence: 99%

Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by high-fat feeding

Zhou

Gillilland

et al. 2020

JCI Insight

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“…They secrete a variety of antimicrobial peptides (AMPs) including α-defensins, Reg3r, lysozyme and contribute to shaping and maintaining the intestinal microbiota [10]. Deficiencies in Paneth cell AMPs were reported to be associated with intestinal barrier failure, leading to the bacterial translocation [11], but Paneth cells have not been thoroughly studied in acute pancreatitis.…”

Section: Introductionmentioning

confidence: 99%

Dysbiosis of intestinal microbiota and decrease in paneth cell antimicrobial peptide level during acute necrotizing pancreatitis in rats

et al. 2017

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ObjectivesIntestinal barrier dysfunction plays an important role in acute necrotizing pancreatitis (ANP) and intestinal microbiota dysbiosis was involved in intestinal barrier failure. Paneth cells protect intestinal barrier and are associated with intestinal microbiota. Here, we investigated changes in intestinal microbiota and antimicrobial peptides of Paneth cells in ileum during ANP.MethodsRats with ANP were established by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct and sacrificed at 24h and 48h, respectively. Injuries of pancreas and distal ileum were evaluated by histopathological score. Intestinal barrier function was assessed by plasma diamine oxidase activity (DAO) and D-lactate. Systemic and intestinal inflammation was evaluated by TNFα, IL-1β and IL-17A concentration by ELISA, respectively. 16S rRNA high throughput sequencing on fecal samples was used to investigate the changes in intestinal microbiota in the ANP group at 48h. Lysozyme and α-defensin5 were measured by real-time PCR, western blot and immunofluoresence.ResultsANP rats had more severe histopathological injuries in pancreas and distal ileum, injured intestinal barrier and increased expression of TNFα, IL-1β and IL-17A in plasma and distal ileum compared with those of the sham-operated (SO) group. Principal component analysis (PCA) showed structural segregation between the SO and ANP groups. Operational taxonomic unit (OTU) number and ACE index revealed decreased microbiota diversity in the ANP group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. At phyla level, Saccharibacteria and Tenericutes decreased significantly. At genus level, Escherichia-Shigella and Phascolarctobacterium increased significantly, while Candidatus_Saccharimonas, Prevotellaceae_UCG-001, Lachnospiraceae_UCG-001, Ruminiclostridium_5 and Ruminococcaceae_UCG-008 decreased significantly. Lysozyme and α-defensin5 mRNA expression levels decreased significantly in ANP group at 48h. Protein expression of lysozyme decreased in ANP groups at 24h and 48h. Meanwhile, the relative abundance of Escherichia-Shigella correlated inversely with the decrease in lysozyme.ConclusionThe disorder in intestinal microbiota and decreases of Paneth cell antimicrobial peptides might participate in the pathogenesis of intestinal barrier dysfunction during ANP.

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“…Paneth cells (PC), which are the typical cells of small intestine, are vitally important components of intestinal mucosal barrier and the main effector cells of small intestinal mucosal barrier. PC contain a variety of antibacterial material such as defensins, lysozyme, and SIgA [ 34 – 36 ], in which both defensins and lysozyme have the spectrum antimicrobial activity and can promote the innate immune response by killing the bacteria and keeping the steady state of intestinal flora [ 37 ]. Antibacterial peptide is alkaline peptide and maintains the balance of intestinal flora and the integrity of intestinal mucosal barrier via interacting with the bacteria in mucosal surface to keep endothelial cells away from being invaded [ 38 – 40 ].…”

Section: CD and Immune Barriermentioning

confidence: 99%

Research Advance in Intestinal Mucosal Barrier and Pathogenesis of Crohn’s Disease

Wang

Dou

et al. 2016

Gastroenterology Research and Practice

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To date, the etiology and pathogenesis of Crohn's disease (CD) have not been fully elucidated. It is widely accepted that genetic, immune, and environment factors are closely related to the development of CD. As an important defensive line for human body against the environment, intestinal mucosa is able to protect the homeostasis of gut bacteria and alleviate the intestinal inflammatory and immune response. It is evident that the dysfunction of intestinal mucosa barriers plays a crucial role in CD initiation and development. Yet researches are insufficient on intestinal mucosal barrier's action in the prevention of CD onset. This article summarizes the research advances about the correlations between the disorders of intestinal mucosal barriers and CD.

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Paneth cells: the hub for sensing and regulating intestinal flora

Cited by 22 publications

References 38 publications

Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by high-fat feeding

Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by high-fat feeding

Dysbiosis of intestinal microbiota and decrease in paneth cell antimicrobial peptide level during acute necrotizing pancreatitis in rats

Research Advance in Intestinal Mucosal Barrier and Pathogenesis of Crohn’s Disease

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