Complexification of In Vitro Models of Intestinal Barriers, A True Challenge for a More Accurate Alternative Approach

Haddad, Michelle J.; Sztupecki, Wendy; Delayre-Orthez, Carine; Rhazi, Larbi; Barbezier, Nicolas; Dépeint, Flore; Anton, Pauline M.

doi:10.3390/ijms24043595

Cited by 22 publications

(6 citation statements)

References 189 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adhesion assays using HT-29 or Caco-2 human intestinal cell lines were performed. These cell lines resemble some aspects of the small intestine, the first with characteristics of a mucus secreting cell and the second being a more absorptive type of cell [23]. The adhesion of Δ eco strain to HT-29 or Caco-2 monolayers were ∼60% and ∼75% lower than the WT strain respectively, while Δ eco + eco rescued this phenotype in both cases (Fig.…”

Section: Resultsmentioning

confidence: 94%

Ecotin protectsSalmonellaTyphimurium against the microbicidal activity of host proteases

Saposnik,

Coria,

Bruno

et al. 2024

Preprint

View full text Add to dashboard Cite

Salmonella entericaserovar Typhimurium causes acute diarrhea upon oral infection in humans. The harsh and proteolytic environment found in the gastrointestinal tract is the first obstacle that these bacteria face after infection. However, the mechanisms that allowSalmonellato survive the hostile conditions of the gut are poorly understood. Theecotingene is found in an extensive range of known phyla of bacteria and it encodes a protein that has been shown to inhibit serine proteases. Thus, in the present work we studied the role ofecotinofSalmonellaTyphimurium in host-pathogen interactions. We found thatSalmonellaTyphimurium Δecotinstrain exhibited lower inflammation in a murine model ofSalmonellainduced colitis. The Δecotinmutant was more susceptible to the action of pancreatin and purified pancreatic elastase. In addition, the lack ofecotinled to impaired adhesion to Caco-2 and HT-29 cell lines, related to the proteolytic activity of brush border enzymes. Besides, Δecotinshowed higher susceptibility to lysosomal proteolytic content and intracellular replication defects in macrophages. In addition, we found Ecotin to have a crucial role inSalmonellaagainst the microbicide action of granules released and neutrophil extracellular traps from human polymorphonuclear leukocytes. Thus, the work presented here highlights the importance ofecotininSalmonellaas countermeasures against the host proteolytic defense system.

show abstract

Section: Resultsmentioning

confidence: 94%

Ecotin protectsSalmonellaTyphimurium against the microbicidal activity of host proteases

Saposnik,

Coria,

Bruno

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Caco-2 cells are a well-established model of the intestinal epithelium with differentiation resulting in a well-organized brush border and a range of molecular transporters and enzymes expressed to mimic the intestinal epithelium in vivo ( 39 ). However, these are colon carcinoma cells cultured to mimic the gut milieu, that is, without the humoral, neurological, muscular or immunological elements associated with the gut lumen environment ( 40 ). There is thus a need for the use of gut organoid models or in vivo feeding studies to investigate the negative impact of neotame on intestinal epithelial cell function, however our studies provide a good indication that this sweetener would significantly disrupt the epithelium in either of these physiological models.…”

Section: Discussionmentioning

confidence: 99%

The artificial sweetener neotame negatively regulates the intestinal epithelium directly through T1R3-signaling and indirectly through pathogenic changes to model gut bacteria

Shil,

Ladeira Faria,

Walker

et al. 2024

Front. Nutr.

View full text Add to dashboard Cite

IntroductionRecent studies have indicated considerable health risks associated with the consumption of artificial sweeteners. Neotame is a relatively new sweetener in the global market however there is still limited data on the impact of neotame on the intestinal epithelium or the commensal microbiota.MethodsIn the present study, we use a model of the intestinal epithelium (Caco-2) and microbiota (Escherichia coli and Enterococcus faecalis) to investigate how physiologically-relevant exposure of neotame impacts intestinal epithelial cell function, gut bacterial metabolism and pathogenicity, and gut epithelium-microbiota interactions.ResultsOur findings show that neotame causes intestinal epithelial cell apoptosis and death with siRNA knockdown of T1R3 expression significantly attenuating the neotame-induced loss to cell viability. Similarly, neotame exposure results in barrier disruption with enhanced monolayer leak and reduced claudin-3 cell surface expression through a T1R3-dependent pathway. Using the gut bacteria models, E. coli and E. faecalis, neotame significantly increased biofilm formation and metabolites of E. coli, but not E. faecalis, reduced Caco-2 cell viability. In co-culture studies, neotame exposure increased adhesion capacity of E. coli and E. faecalis onto Caco-2 cells and invasion capacity of E. coli. Neotame-induced biofilm formation, E.coli-specific Caco-2 cell death, adhesion and invasion was identified to be meditated through a taste-dependent pathway.DiscussionOur study identifies novel pathogenic effects of neotame on the intestinal epithelium or bacteria alone, and in co-cultures to mimic the gut microbiome. These findings demonstrate the need to better understand food additives common in the global market and the molecular mechanisms underlying potential negative health impacts.

show abstract

“…The cell inhibition concentrations of MRK-107 were 2.40 µM for Caco-2 and 1.13 µM for HT-29, representing high anticancer activity [ 36 ]. Both cell lines originate from the same region of the colon but have specific characteristics in terms of transepithelial/endothelial resistance [ 37 ]. For instance, the physiological barrier of Caco-2 cells is four times more resistant than that of HT-29 cells.…”

Section: Discussionmentioning

confidence: 99%

Selenylated Imidazo [1,2-a]pyridine Induces Apoptosis and Oxidative Stress in 2D and 3D Models of Colon Cancer Cells

Gomes,

Zubieta,

Guilhermi

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

Colon cancer incidence rates are increasing annually, a scenario aggravated by genetic and epigenetic alterations that promote drug resistance. Recent studies showed that novel synthetic selenium compounds are more efficient and less toxic than conventional drugs, demonstrating biocompatibility and pro-oxidant effects on tumor cells. This study aimed to investigate the cytotoxic effect of MRK-107, an imidazo [1,2- a]pyridine derivative, in 2D and 3D cell culture models of colon cancer (Caco-2 and HT-29). Sulforhodamine B results revealed a GI50 of 2.4 µM for Caco-2, 1.1 µM for HT-29, and 22.19 µM for NIH/3T3 in 2D cultures after 48 h of treatment. Cell recovery, migration, clonogenic, and Ki-67 results corroborated that MRK-107 inhibits cell proliferation and prevents cell regeneration and metastatic transition by selectively reducing migratory and clonogenic capacity; non-tumor cells (NIH/3T3) re-established proliferation in less than 18 h. The oxidative stress markers DCFH-DA and TBARS revealed increased ROS generation and oxidative damage. Caspases-3/7 are activated and induce apoptosis as the main mode of cell death in both cell models, as assessed by annexin V-FITC and acridine orange/ethidium bromide staining. MRK-107 is a selective, redox-active compound with pro-oxidant and pro-apoptotic properties and the capacity to activate antiproliferative pathways, showing promise in anticancer drug research.

show abstract

Complexification of In Vitro Models of Intestinal Barriers, A True Challenge for a More Accurate Alternative Approach

Cited by 22 publications

References 189 publications

Ecotin protectsSalmonellaTyphimurium against the microbicidal activity of host proteases

Ecotin protectsSalmonellaTyphimurium against the microbicidal activity of host proteases

The artificial sweetener neotame negatively regulates the intestinal epithelium directly through T1R3-signaling and indirectly through pathogenic changes to model gut bacteria

Selenylated Imidazo [1,2-a]pyridine Induces Apoptosis and Oxidative Stress in 2D and 3D Models of Colon Cancer Cells

Contact Info

Product

Resources

About