Protective effects of Acetobacter ghanensis against gliadin toxicity in intestinal epithelial cells with immunoregulatory and gluten-digestive properties

• Published in: European journal of nutrition Vol. 62; no. 2; pp. 605 - 614
• Main Authors: Doguer, Caglar, Akalan, Hande, Tokatlı Demirok, Nazan, Erdal, Berna, Mete, Rafet, Bilgen, Turker
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2023; Springer Nature B.V
• Subjects: Acetobacter; Acetobacter ghanensis; Caco-2 Cells; Celiac Disease; Cell culture; Chemistry; Chemistry and Materials Science; Enzyme-linked immunosorbent assay; Epithelial Cells; Gliadin; Gluten; Glutens; Humans; Immunoregulation; Interleukin 6; Interleukin-6 - metabolism; Intestinal Mucosa - metabolism; Intestine; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; mRNA; Nutrition; Original Contribution; Peripheral blood mononuclear cells; Probiotics; Toxicity; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Zonula occludens-1 protein; Probiotics; Celiac disease; Caco-2 cells; Acetobacter ghanensis
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-022-03015-6

Purpose
The aim of this study was to establish whether
Acetobacter ghanensis
, the probiotic characteristics of which were evaluated previously, attenuates gliadin-induced toxicity in intestinal epithelial cells with gluten-digestive and immunoregulatory properties.
Methods
A co-culture model of human intestinal epithelial cell (Caco-2) monolayers on top of peripheral blood mononuclear cells (PBMCs) obtained from patients with celiac disease (CD) was established. The gluten-digestive properties of
A. ghanensis
were determined by checking bacterial growth in a medium containing gluten as the main nitrogen source. The mRNA levels of genes encoding TJ-associated proteins were measured by quantitative real-time PCR (qRT-PCR). The concentrations of IL-6 and TNFα were determined by enzyme-linked immunosorbent assay (ELISA).
Results
We found that PT-gliadin disrupted intestinal barrier integrity by modulating the expression of TJ-associated genes encoding zonulin (increased by ~ 60%), zonula occludens-1 (
ZO-1
) (decreased by ~ 22%), and occludin (decreased by ~ 28%) in Caco-2 cells. Furthermore, PT-gliadin treatment in Caco-2 cells was associated with increased concentrations of IL-6 (~ 1.6-fold) and TNFα (~ twofold) from PBMCs. These modulatory effects of PT-gliadin, however, were suppressed when Caco-2 cells were subjected to
A. ghanensis
in the presence of PT-gliadin. As a factor underlying these protective effects, we showed that
A. ghanensis
could digest gluten peptides.
Conclusions
To our knowledge, the current study is the first to demonstrate that
A. ghanensis
improves intestinal barrier functions by attenuating the modulatory effects of PT-gliadin with immunoregulatory and gluten-digestive properties.