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Calcium Phosphate Particles in Stomach Are Highly Porous; Capable of Trapping & Transporting Antigens to Instestinal Immune Cells; May Be Involved in Diseases Like Crohn’s & Ulcerative Colitis

There are numerous studies related to the absorption of nutrients from the stomach because understanding what happens in our digestive system is crucial, for example, in order to be able to avoid in the future some of the diseases that affect part of the population to a lesser or greater extent. In the UK, a group of researchers from the Medical Research Council, led by Professor Dr. Jonathan J. Powell, have been working along these lines for years. They have led various studies of this type, the latest of which is a study in which 16 institutions from various countries participated, including the University of Cadiz in Spain. As a result of this international study, an article entitled “An Endogenous Nanomineral Chaperones Luminal Antigen and Peptidoglycan to Intestinal Immune Cells” has been published in the April 2015 issue of Nature Nanotechnology. In this article, the formation of calcium phosphate in the stomach, its function, and its direct relationship with the immune system are analyzed from an innovative perspective. In fact, the origin of digestive diseases such as ulcerative colitis or Crohn’s disease is possibly explained, opening up a new line of research, unknown until now, and which, in the long term, could result in the development of drugs that may alleviate the dire effects of these diseases. In order to better understand the important role of Spain’s Dr. Juan Carlos Hernández-Garrido (photo) in this study, it is important to know that the University of Cadiz is an international reference point in electronic microscopy and there are very few experts in the tri-dimensional characterization of materials using electronic microscopy, an area in which Dr. Hernández-Garrido is a specialist. In addition, it should be noted that Dr. Hernández-Garrido had previously worked with the University of Cambridge authors, when he had conducted research at the University of Cambridge earlier in his career. “Up until now, we had always worked on the analysis of nutrients of biomineral origin using conventional techniques that provided two-dimensional images or planes of these particles, something that at this point was insufficient,” Dr. Hernández-Garrido said.

“Objects in nature are three-dimensional; nowadays if you want to characterize an object, you have to do so, keeping as closely as possible to its actual morphology, its real shape, its size, its geometry… and to do this you must use a three-dimensional characterization because the structure, the properties, and the functions of these objects are all inter-related. If you know the structure of something, you can [likely] understand its properties and you can understand its functions,” explains Dr. Hernández-Garrido.

Therefore, “I decided to accept this challenge. They needed a three-dimensional characterization and I was in a position to provide one, although I had never done this with particles of biological origin before, I took on this work.”
It took several years to carry out this 3D analysis, but the results were highly significant. The researchers were able to observe a mineralization effect in which the calcium and phosphorus ions joined together in the stomach to form calcium phosphate, something which was not a new observation.

What was truly new was that this 3D visualization “revealed, in high resolution, that what had been seen in a conventional image and that we had interpreted as a dense, compact particle, in fact, was a particle with many small cavities; it had a highly porous internal structure.”

The most interesting thing about this point is that “by demonstrating that these particles are highly porous, we are opening up the possibility that, during their formation from the joining of calcium and phosphorus ions, various antigens could become trapped in their [the calcium phosphate nanoparticle’s] interior. In fact, we already knew, from work by other researchers, that these calcium phosphate particles are consumed by immune system cells via the lymphoid tissue that lines the intestines,” Dr. Hernández-Garrido said.

In this way, the particle itself is acting as a kind of transporter or carrier to what is known as the intestinal epithelium, the lumen, which is where there is a structure that allows the absorption of nutrients.

In other words, “the calcium phosphate nanoparticles can trap antigens (and certain other macromolecules such as proteins) and take them to this part of the intestine, which means that these biominerals not only help in the absorption of nutrients, but that they are also antigen transporters, and are therefore key in the creation of an immunological effect that we had been unable to see until now,” points out Dr. Hernández-Garrido.

Thus, at the University of Cadiz “we have focused on showing the real structure and morphology of these biominerals, something that up until now, had only been suspected,” he said.

This being the case, on understanding and proving the real structure of these particles, their function focusing on transferring nutrients and, in turn, aiding in their absorption was confirmed.

This, in turn, led scientists to carry out a series of tests on mice that determined that “an imbalance of phosphorus and calcium can cause an incorrect or deficient absorption of nutrients. In other words, if there is a calcium deficiency, for example, not enough calcium phosphate could be generated, or if it did not have the correct structure, we would not be able to transfer antigens to the intestinal epithelium and consequently we would lower our defense mechanisms in the intestine, which could explain the origin of determined inflammatory intestinal diseases such as ulcerative colitis or Crohn’s disease.”

This study has succeeded in taking one more step towards discovering the origin of certain diseases, although there is still m work ahead before we can combat these diseases that would appear to be associated with a calcium deficiency.

[Press release] [Nature Nanotechnology abstract] [Nature Nanotechnology News & Views abstract--"Gut Immunology: Nanoparticles Ferry Gut Antigens"]