Microparticles and their impact on intestinal immunity

Our plain-English summary of Microparticles and their impact on intestinal immunity, by H.M. Becker, M.M. Bertschinger, G. Rogler (Digestive Diseases, 2012).

The study

• Authors: H.M. Becker, M.M. Bertschinger, G. Rogler
• Journal: Digestive Diseases
• Published: 2012;30 Suppl 3:47-54
• Type of article: Review
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Microparticles are small (<1 µm), nonbiological particles that are used in many areas of daily life. As food additive they are used as anticaking agents or food colorants. The most common food-derived ingested compounds are aluminium silicate and titanium dioxide (TiO(2)), the latter being a white pigment used in toothpaste or sugar toppings. The increasing abundance of microparticles in the Western diet raises the question of the potential risks associated with gastrointestinal diseases such as Crohn's disease (CD). Accumulation of particles has been shown in cells of Peyer's patches, but it is not clear whether this also has pathological effects. NLRP3 is a member of the intracellular pattern recognition receptor family and it is part of the inflammasome, a multiprotein complex containing caspase-1 which activates the proinflammatory cytokines interleukin (IL)-1β and IL-18. With regard to recent findings identifying small particles such as asbestos and monosodium urate as NLRP3 activators, TiO(2) may be another potential target for inflammasome studies. We found that macrophage-like cells readily take up TiO(2) after 6 h. Incubation of cells with TiO(2) resulted in the assembly of NLRP3 with caspase-1. This inflammasome assembly correlated with secretion of IL-1β. In intestinal epithelial cells, TiO(2) also was found to be ingested. The counting of particles localized intracellularly revealed a dose-dependent increase of TiO(2)-positive cells. This points to the fact that in humans with a leaky intestinal barrier (such as IBD patients), TiO(2) microparticles may be taken up by macrophages and intestinal epithelial cells, may activate the inflammasome and induce IL-1β and IL-18 secretion. This may aggravate inflammation in susceptible individuals.

Copyright © 2012 S. Karger AG, Basel.

In plain English

This article mainly reviewed how tiny non-living particles used as food additives, especially titanium dioxide (TiO2, additive E171) and aluminium silicate, might affect gut immunity in inflammatory bowel disease such as Crohn's disease. It focused on NLRP3, part of a protein complex (the inflammasome) that activates the enzyme caspase-1, which cuts the precursors of the inflammatory signals IL-1 beta and IL-18 so the cell can release them. Asbestos was not studied here. It appeared only in earlier research the authors cited as a known NLRP3 activator. The authors briefly described their own laboratory work on cultured cells, giving only limited detail about methods and results. They reported that macrophage-like cells took up TiO2 after 6 hours and that intestinal lining cells also took it in, with more particle-containing cells at higher doses. Low concentrations of TiO2 led to inflammasome assembly and release of the inflammatory signals. High doses produced reactive oxygen species, and the particles did not rupture lysosomes. The authors concluded that in people with a leaky gut barrier, such as inflammatory bowel disease patients, TiO2 may worsen inflammation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published research on food-derived microparticles and the NLRP3 inflammasome in the gut, with a brief, non-detailed report of the authors' own in vitro (cell culture) findings
• Who was studied: Macrophages (macrophage-like cells) and intestinal epithelial cells grown in the laboratory. Cell lines, numbers of experiments, place and dates are not given.
• Exposure: Titanium dioxide (TiO2) microparticles at low and high concentrations. The exact doses used on cells are not stated. Asbestos was not tested in this work. It is named only as an NLRP3 'danger signal' identified in earlier cited studies.
• Main results:
  • Macrophage-like cells took up TiO2 after 6 hours
  • In intestinal epithelial cells, counting of particles inside cells showed a dose-dependent increase in TiO2-positive cells (no figures given)
  • In macrophages and intestinal epithelial cells, low concentrations of TiO2 led to assembly of the NLRP3 inflammasome, and caspase-1, IL-1 beta and IL-18 were activated and secreted
  • High doses of TiO2 caused generation of reactive oxygen species in the tested cell types
  • Uptake of TiO2 did not lead to lysosomal rupture, unlike findings others reported for silica crystals
• The authors' conclusion: The authors concluded that in people with a leaky intestinal barrier, such as IBD patients, TiO2 microparticles may be taken up by macrophages and intestinal epithelial cells and may activate the inflammasome. They also concluded this may aggravate inflammation in susceptible individuals.
• Limitations the authors state:
  • The authors stated that the long-term impact of dietary microparticles such as TiO2 and aluminium silicate has not been studied and that risk evaluation is inconclusive

Topics

Medical terms in this study, explained in our Lexicon: Silicate, Cytokine, Macrophage, Inflammation.

Related studies

• Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β — A.S. Yazdi, G. Guarda, et al. (2010)
• The NLRP3 inflammasome is activated by nanoparticles through ATP, ADP and adenosine — L. Baron, A. Gombault, et al. (2015)
• Chemical agents and the immune response — M.I. Luster, G.J. Rosenthal (1993)
• Purification of staphylocidal beta-lysin from rabbit serum — F.B. Johnson, D.M. Donaldson (1968)
• Light and electron microscope studies of the rat digestive tract following prolonged and short-term ingestion of chrysotile asbestos — R. Jacobs, J. Humphrys, et al. (1978)
• The short-term effects of chronic asbestos ingestion in rats — R.E. Bolton, J.M. Davis (1976)

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