Nanoplastics: A New Threat for Human Health?

We are living in a new, unofficial but significant unit of geological time called Anthropocene, which is characterized by the impact that the human activity have on the planet’s climate and ecosystems [1]. Some researchers even think that Plasticene will be a better descriptor for the times we are living, as plastics are ubiquitous, cost-effective, multipurpose materials that have changed our lives since they were discovered and incorporated to our lives. Nevertheless, if we continue producing and discarding plastics inefficiently, the slow degradation rates and pervasiveness of nanoplastics guarantee a continuous supply of polymer shreds into marine and terrestrial organisms.

What are nanoplastics? Decay or large plastics lead to less than 5mm pieces called microplastics which, eventually, can be further degraded into nanoplastics, a micrometric scale pieces of plastic. As plastics contain components such as catalysts, solvents, stabilizers, flame retardants or pigments, during the plastic decay those elements will be liberated to the environment, worsening the effects of plastic pollution [2].

Plastic accumulation has multiple environmental effects as they provide attachment surfaces for microorganisms, enhances the incorporation of plastic fragments into marine and terrestrial animals, and once bioaccumulated, may impair endogenous endocrine and neuroimmune crosstalk in vertebrates.

Sources of nanoplastics. Gangadoo S, et al. Nanoplastics and their analytical characterization and fate in the marine environment: From source to sea. Sci Total Environ. 2020 Aug 25; 732:138792. DOI: 10.1016/j.scitotenv.2020.138792.

Most of the health-related issues of plastic pollution has been evaluated in aquatic environments using animal models, or using mammalian cell lines for in vitro analysis of plastic exposure relate to cytotoxicity and altered gene expression [3]. Despite humans usually ingest and sometimes inhale these nanoplastics, their long-term impact in human health has not been thoroughly assessed. Nanoplastics could affect the composition and diversity of our microbiome, and recent research pinpointed the effect of gut microbiota on endocrine, immune and nervous systems [4-6]. In addition to teaching the immune system about differences between commensal and pathogenic threats, microorganisms also respond to stress and manufacture precursors of neurotransmitters that may affect behavior. Furthermore, nanoplastics clumped in the gut epithelia can eventually cross the endothelial barriers and then be transported intro the erythrocytes to distant tissues, where they can cross cellular membranes and stress cells [7]. Nanoplastics have the ability to travel along the intracellular spaces by paracellular transport, and they can also be transported by microfold cells (M cells) towards lymphatic capillaries, thus reaching lymphoid tissues.

Although researchers estimated that up to 90% of the ingested nanoplastics are excreted, the remaining leftover may induce cytotoxicity, arrest cell cycles and increase the expression of inflammatory markers within the immune system cell populations. Gut local inflammation can compromise the gastrointestinal functionality, perturb their endocrine regulations, and even lead to dysbiosis or abnormal gut microbiota reactivity [8]. The structure and composition of human microbiome is influenced by the diet habits and culinary traditions of different populations, the type and intensity of other environmental stressors and by stochastic perturbations of microbiome communities which will balance the ratio between commensality and pathogenicity within the gut microorganisms. Stressed organisms may show a greater diversity or turnover of microbial species than healthy organisms, and the effects of nanoplastics may contribute to microbiome changes.

In vitro experiments assessing the effect of nanoplastics (up to 50 nm) in human cells showed that once absorbed, plastic nanoparticles may reach the cell nucleus where they exert mildly or no effects depending on the cellular line. Monocytic cells may avidly ingest plastic nanoparticles with no adverse effects, whereas other immune-related cell lines suffer from enhanced cellular reactive oxygen species (ROS) production and DNA damage [9].  It is worth noting that accumulated nanoplastics may diminish food consumption due to microbiome and digestive imbalances, or may stimulate the appetite when inflammatory reactions unfold and the activation of stress hormonal regulators overcome normal functioning. This is in line with some in vitro experiments where human cell lines exposed to nanoplastics had an enhanced expression of inflammatory regulators which can alter the immune function. 

Potential effects of different sized degraded polymeric material, which can be further enhanced when chemicals are present at the same time. da Costa JP, Santos PSM, Duarte AC, Rocha-Santos T. (Nano)plastics in the environment - Sources, fates and effects. Sci Total Environ. 2016 Oct 1;566-567:15-26. DOI: 10.1016/j.scitotenv.2016.05.041.

Nevertheless, more in vivo studies are necessary to precisely examine the effects of nanoplastics in human physiology, together with an accurate quantification of environmental nanoparticle loads and a more standardize methodology to address the confounding variability of in vitro approaches.

Experimentation animal models may help to understand what is going on in our guts when they are full of plastics. Dysbiotic mice, for example, have an altered expression of brain neurotransmitters, and besides neurotoxic effects, nanoplastics may contribute to their neuronal disfunction due to the blood-bran barrier permeability to polystyrene nanoparticles. The biggest concern regards the inhalation of synthetic fibers or products of abrasion that will reach the lungs, where immune cells engage in the internalization and translocation of plastic bits to lymphatic and blood vessels. Within the lungs, mildly inflammatory reactions may eventually become chronic and seriously impair its function [10]. Studies in mice reveal that relocating nanoplastics through cellular hitchhiking from pulmonary reservoirs may clog blood vessels, cross the placental barrier and promote accumulation in gastrointestinal tissues, liver and kidney, leading to dysregulation of metabolism and excretion processes.

A whole organism approach to analyze long-term effects of nanoplastics in neuro immuno endocrine axis in humans is still in its infancy, and future developments in this direction will be very valuable for global health. Phenotypic plasticity will determine the adaptive outcome to persistent exposure to nanoplastics and, although no long-term cross generational studies of plastic pollution have been carried out in human populations, the persistence of toxic compounds present in populations exposed to wastewater chemicals may deplete the genetic pool available to detoxify contaminants or, alternatively, produce novel genes to cope with the stressor [11].  

It is our responsibility to adopt the necessary regulation to prevent plastics being released to the environment, as they will be potentially harmful for our health in the near future. In the meanwhile, science will always try to figure it out what is happening inside our bodies to solve these new generation health issues.

References:

1. Subramanian, M., Humans versus Earth: the quest to define the Anthropocene. Nature, 2019. 572(7768): p. 168-170.

2. Oliveira, M., M. Almeida, and I. Miguel, A micro(nano)plastic boomerang tale: A never ending story? TrAC Trends in Analytical Chemistry, 2019. 112: p. 196-200.

3. de Sa, L.C., et al., Studies of the effects of microplastics on aquatic organisms: What do we know and where should we focus our efforts in the future? Sci Total Environ, 2018. 645: p. 1029-1039.

4. Dinan, T.G. and J.F. Cryan, The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterol Clin North Am, 2017. 46(1): p. 77-89.

5. Shi, N., et al., Interaction between the gut microbiome and mucosal immune system. Mil Med Res, 2017. 4: p. 14.

6. Farzi, A., E.E. Frohlich, and P. Holzer, Gut Microbiota and the Neuroendocrine System. Neurotherapeutics, 2018. 15(1): p. 5-22.

7. Lehner, R., et al., Emergence of Nanoplastic in the Environment and Possible Impact on Human Health. Environ Sci Technol, 2019. 53(4): p. 1748-1765.

8. Fackelmann, G. and S. Sommer, Microplastics and the gut microbiome: How chronically exposed species may suffer from gut dysbiosis. Mar Pollut Bull, 2019. 143: p. 193-203.

9. Hoffman, B.U. and E.A. Lumpkin, A gut feeling. Science, 2018. 361(6408): p. 1203-1204.

10. Bierkandt, F.S., et al., The impact of nanomaterial characteristics on inhalation toxicity. Toxicol Res (Camb), 2018. 7(3): p. 321-346.

11. Marques da Cunha, L., et al., No additive genetic variance for tolerance to ethynylestradiol exposure in natural populations of brown trout (Salmo trutta). Evol Appl, 2019. 12(5): p. 940-950.

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