Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor–mediated Dysbiosis

Pickert, Geethanjali; Wirtz, Stefan; Matzner, Johannes; Ashfaq–Khan, Muhammad; Heck, Rosario; Rosigkeit, Sebastian; Thies, Dorothe; Surabattula, Rambabu; Ehmann, Dirk; Wehkamp, Jan; Noor, Muhammad Aslam; He, Gui-Wei; Weigert, Andreas; Foerster, Friedrich; Klotz, Luisa; Frick, Julia-Stefanie; Becker, Christoph; Bockamp, Ernesto; Schuppan, Detlef

doi:10.1053/j.gastro.2020.03.064

Cited by 48 publications

(63 citation statements)

References 48 publications

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“…Ileal transcript levels of the monocyte-macrophage activation marker interleukin 1 β (IL1β) were comparable in all mice, regardless of the dietary regime ( Figure 3 f), whereas C–C motif chemokine ligand 2 (CCL2), a chemokine recruiting monocytes and macrophages to sites of injury, was significantly increased in all ATI-fed groups, compared to the mice fed an ATI- and gluten-free diet ( Figure 3 g), in accord with our data in other models of disease [ 13 , 25 , 26 ].…”

Section: Resultssupporting

confidence: 87%

“…Moreover, as shown in Figure 4a, ATIs led to a shift towards a lowered Bacteroidetes to Firmicutes ratio, with a clear dose-dependent effect and significant cumulative effect when combined with gluten (p = 0.0013 and 0.0003). Additionally, ATI reduced Bifidobacteria in line with our prior study in mice with inflammatory bowel disease [26] (Figure 4b). On a gluten-containing background, no further changes were measured and the Lactobacilli or the Lactobacilli/ Enterococci ratio appeared not to be changed at all by gluten (Figure 4c,d).…”

Section: Ati-induced Changes In the Gutsupporting

confidence: 91%

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Dietary Wheat Amylase Trypsin Inhibitors Impact Alzheimer’s Disease Pathology in 5xFAD Model Mice

Guilherme

Zevallos

Pesi

et al. 2020

IJMS

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Wheat amylase trypsin inhibitors (ATIs) represent a common dietary protein component of gluten-containing cereals (wheat, rye, and barley). They act as toll-like receptor 4 ligands, and are largely resistant to intestinal proteases, eliciting a mild inflammatory response within the intestine after oral ingestion. Importantly, nutritional ATIs exacerbated inflammatory bowel disease and features of fatty liver disease and the metabolic syndrome in mice. For Alzheimer’s disease (AD), both inflammation and altered insulin resistance are major contributing factors, impacting onset as well as progression of this devastating brain disorder in patients. In this study, we evaluated the impact of dietary ATIs on a well-known rodent model of AD (5xFAD). We assessed metabolic, behavioral, inflammatory, and microbial changes in mice consuming different dietary regimes with and without ATIs, consumed ad libitum for eight weeks. We demonstrate that ATIs, with or without a gluten matrix, had an impact on the metabolism and gut microbiota of 5xFAD mice, aggravating pathological hallmarks of AD. If these findings can be translated to patients, an ATI-depleted diet might offer an alternative therapeutic option for AD and warrants clinical intervention studies.

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Section: Resultssupporting

confidence: 87%

Section: Ati-induced Changes In the Gutsupporting

confidence: 91%

Dietary Wheat Amylase Trypsin Inhibitors Impact Alzheimer’s Disease Pathology in 5xFAD Model Mice

Guilherme

Zevallos

Pesi

et al. 2020

IJMS

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“…The 4 samples with the highest DNA content were analyzed by 16S-based metagenomic sequencing as described elsewhere [ 54 ]. The V3–V4 region of the bacterial 16S rRNA gene was amplified by PCR (35 cycles; 98 °C for 15 s, 58 °C for 20 s, 72 °C for 40 s; NEB Next Ultra II Q5 Master Mix, New England Biolabs, Ipswich, MA, USA) using template DNA and region-specific primers (containing barcodes and Illumina flow cell adaptor sequences; Eurofins Genomics, Munich, Germany).…”

Section: Methodsmentioning

confidence: 99%

Neutrophil Extracellular Traps Promote the Development and Growth of Human Salivary Stones

Mantsopoulos

Koch

Weidner

et al. 2020

Cells

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Salivary gland stones, or sialoliths, are the most common cause of the obstruction of salivary glands. The mechanism behind the formation of sialoliths has been elusive. Symptomatic sialolithiasis has a prevalence of 0.45% in the general population, is characterized by recurrent painful periprandial swelling of the affected gland, and often results in sialadenitis with the need for surgical intervention. Here, we show by the use of immunohistochemistry, immunofluorescence, computed tomography (CT) scans and reconstructions, special dye techniques, bacterial genotyping, and enzyme activity analyses that neutrophil extracellular traps (NETs) initiate the formation and growth of sialoliths in humans. The deposition of neutrophil granulocyte extracellular DNA around small crystals results in the dense aggregation of the latter, and the subsequent mineralization creates alternating layers of dense mineral, which are predominantly calcium salt deposits and DNA. The further agglomeration and appositional growth of these structures promotes the development of macroscopic sialoliths that finally occlude the efferent ducts of the salivary glands, causing clinical symptoms and salivary gland dysfunction. These findings provide an entirely novel insight into the mechanism of sialolithogenesis, in which an immune system-mediated response essentially participates in the physicochemical process of concrement formation and growth.

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“…The 4 samples with the highest DNA content were analyzed by 16S-based metagenomic sequencing as described elsewhere 70 . The V3-V4 region of the bacterial 16S rRNA gene was ampli ed by PCR (35 cycles; 98°C for 15 seconds, 58°C for 20 seconds, 72°C for 40 seconds; NEB Next Ultra II Q5 Master Mix, New England Biolabs, Ipswich, USA) using template DNA and region-speci c primers (containing barcodes and Illumina ow cell adaptor sequences; Euro ns Genomics, Munich, Germany).…”

Section: Experimental Methodsmentioning

confidence: 99%

Development and Growth of Human Salivary Stones by Neutrophil Extracellular Traps

Mantsopoulos

Koch

Weidner

et al. 2020

Preprint

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Salivary gland stones, or sialoliths, are the most common cause of the obstruction of salivary glands. Symptomatic sialolithiasis has a prevalence of 0.45% in the general population, is characterized by recurrent painful periprandial swelling of the affected gland and often results in sialadenitis with the need for surgical intervention. The mechanism behind the formation of sialoliths has been elusive. Here we show that neutrophil extracellular traps (NETs) initiate the formation and growth of sialoliths. The deposition of neutrophil granulocyte extracellular DNA around small crystals results in their dense aggregation, and the subsequent mineralization creates alternating layers of dense mineral, predominantly calcium salt deposits and DNA. Further agglomeration and appositional growth of these structures promotes the development of macroscopic sialoliths that finally occlude the efferent ducts of the salivary glands, causing clinical symptoms and salivary gland dysfunction. These findings provide an entirely novel insight into the mechanism of sialolithogenesis in which an immune system mediated response essentially participates in the physico-chemical process of concrement formation and growth.

show abstract

Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor–mediated Dysbiosis

Cited by 48 publications

References 48 publications

Dietary Wheat Amylase Trypsin Inhibitors Impact Alzheimer’s Disease Pathology in 5xFAD Model Mice

Dietary Wheat Amylase Trypsin Inhibitors Impact Alzheimer’s Disease Pathology in 5xFAD Model Mice

Neutrophil Extracellular Traps Promote the Development and Growth of Human Salivary Stones

Development and Growth of Human Salivary Stones by Neutrophil Extracellular Traps

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