Effect of dietary additives on intestinal permeability in both <i>Drosophila</i> and a human cell co-culture

Pereira, Matthew T.; Malik, Mridu; Nostro, Jillian A.; Mahler, Gretchen J.; Musselman, Laura Palanker

doi:10.1242/dmm.034520

Cited by 37 publications

(36 citation statements)

References 139 publications

(201 reference statements)

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“…E. coli is primarily present in the colon; however, the distal ileum has been shown to contain more Gram-negative than Gram-positive bacteria (5). Our previous work demonstrated increased intestinal permeability in the in vitro Caco-2/HT29-MTX model, and a reduced gut size in Drosophila melanogaster model in response to a high sugar diet, which was rectified with L. rhamnosus (15). Similarly, in this study we found that intestinal permeability was significantly reduced upon exposure to L. rhamnosus ( Figure 5A) and E. coli (Figure 3A) under HG conditions.…”

Section: Discussionmentioning

confidence: 93%

Bacteria Remediate the Effects of Food Additives on Intestinal Function in an in vitro Model of the Gastrointestinal Tract

et al. 2020

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As the site of nutrient absorption, the small intestine is continuously exposed to preservatives and additives present in consumed food. While the effects of diet on the lower gastrointestinal tract are widely studied, the effects of food additives on the small intestinal epithelium and microbiota are less clearly understood. The goal of this work was to develop and establish a physiologically relevant model of the upper gastrointestinal tract to study the complex interactions between food additives, individual bacterial species, and intestinal function. To achieve this, an in vitro model incorporating simulated digestion, human intestinal epithelial cells, and the commensal, Gram-positive Lactobacillus rhamnosus, or the opportunistic, Gram-negative Escherichia coli was developed. This model was used to assess intestinal permeability and alkaline phosphatase activity following exposure to high glucose (HG), salt, emulsifier (TWEEN 20), food (milk chocolate candies) or chemical grade titanium dioxide nanoparticles (TiO 2-NP), and food (whole wheat bread) or chemical grade gluten. It was found that HG increased intestinal permeability, the presence of bacteria remediated the negative effects of HG on intestinal permeability, and a decrease in permeability and IAP activity was observed with increasing concentration of TWEEN 20 both in the presence and absence of bacteria. While L. rhamnosus influenced the activity of intestinal alkaline phosphatase and tight junction protein distribution, E. coli produced indole to reinstate intestinal permeability. The source of TiO 2 and gluten led to altered impacts on permeability and IAP activity. The growth of E. coli and L. rhamnosus was found to depend on the type of food additive used. Overall, the presence of bacteria in the in vitro model influenced the effects of food additives on intestinal function, suggesting a complex association between diet and upper GI microbiota. This model provides a method to study small intestinal function and host-microbe interactions in vitro in both healthy and diseased conditions.

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Section: Discussionmentioning

confidence: 93%

Bacteria Remediate the Effects of Food Additives on Intestinal Function in an in vitro Model of the Gastrointestinal Tract

et al. 2020

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“…Intestinal barrier disruption in flies is known to impact survival 54 . Thus, we examined whether the reduced survival of irradiated flies was due to damage to intestinal tissue.…”

Section: Ionizing Radiation Disrupts Intestinal Integrity and Inducesmentioning

confidence: 99%

Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal permeability and survival in Drosophila

Sharma

Akagi

Pattavina

et al. 2020

Sci Rep

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Exposure to genotoxic stress by environmental agents or treatments, such as radiation therapy, can diminish healthspan and accelerate aging. We have developed a Drosophila melanogaster model to study the molecular effects of radiation-induced damage and repair. Utilizing a quantitative intestinal permeability assay, we performed an unbiased GWAS screen (using 156 strains from the Drosophila Genetic Reference Panel) to search for natural genetic variants that regulate radiation-induced gut permeability in adult D. melanogaster. From this screen, we identified an RNA binding protein, Musashi (msi), as one of the possible genes associated with changes in intestinal permeability upon radiation. The overexpression of msi promoted intestinal stem cell proliferation, which increased survival after irradiation and rescued radiation-induced intestinal permeability. In summary, we have established D. melanogaster as an expedient model system to study the effects of radiation-induced damage to the intestine in adults and have identified msi as a potential therapeutic target.

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“…Cell cultures were incubated at 37°C in a humidi ed atmosphere with 5 % CO 2 and 95 % air. In vitro experiments, the CFs and CMs were cultured with LPS (100 ng/mL) [20] and different concentrations of glucose: 5.5 mmol/L glucose (control) and 30 mmol/L glucose (HG) [21]for 72 h at 37°C with 5% CO 2 , respectively.…”

Section: Methodsmentioning

confidence: 99%

Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation

Zhang¹,

Zhang²,

Luo³

et al. 2020

Preprint

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Background: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-associated diseases. However, whether age-associated gut microbial dysbiosis contributes to AF is still unknown. The aim of this study was to evaluate the effect of gut microbiota on the susceptibility of aging-induced AF and to elucidate the underlying mechanisms. Results: The gut microbiota profiling of fecal samples in aged (22-24 months old) and young (2-3 months old) rats was performed by 16S ribosomal RNA gene analysis. A rat model of fecal microbiota transplantation (FMT) was established for analyzing the possible role of age-associated gut microbial dysbiosis in AF. Here, we found that aging process led to marked shift of the microbiota spectrum. The microbiota in young rats following FMT resembled that of aged microbiota and transmitted the increased AF susceptibility by elevation of circulating lipopolysaccharide (LPS). The mechanism for LPS-driven atrial pro-arrhythmic action was dependent on the activation of atrial nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing (NLRP3)-inflammasome. Inhibition of inflammasome by MCC950 resulted in lower atrial fibrosis and AF susceptibility. In addition, atrial fibrosis, plasma LPS concentration, plasma glucose to oral glucose tolerance test (OGTT), intestinal permeability, and gut pathology were significantly increased in elderly human subjects. Finally, altering the microbiota in aged recipient to resemble that of young restored the intestinal barrier dysfunction and LPS and impaired glucose tolerance, and the worse outcomes of aged dysbiosis on atrial fibrosis and AF susceptibility were abrogated. Conclusions: These data suggest that age-associated microbial dysbiosis induces circulating LPS and impairs glucose tolerance, and thereby promotes AF susceptibility through enhanced activity of atrial NLRP3-inflammasome.

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Effect of dietary additives on intestinal permeability in both Drosophila and a human cell co-culture

Cited by 37 publications

References 139 publications

Bacteria Remediate the Effects of Food Additives on Intestinal Function in an in vitro Model of the Gastrointestinal Tract

Bacteria Remediate the Effects of Food Additives on Intestinal Function in an in vitro Model of the Gastrointestinal Tract

Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal permeability and survival in Drosophila

Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation

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