Oligomer nanoparticle release from polylactic acid plastics catalysed by gut enzymes triggers acute inflammation

Abstract

Although the risks of microplastics in environmental exposure and human health are being increasingly studied, little is known about the behavior of "eco-friendly" bioplastics in humans, especially their effects on our gastrointestinal tract. Here we demonstrate that enzymatic hydrolysis of bio-based polylactic acid (PLA) microplastics rapidly generates an excess of nanoplastic particles by competing for triglyceridedegrading lipase during gastrointestinal processes. These tiny nanoparticles are oligomers formed by hydrophobic-driven self-aggregation, and upon exposure the oligomers and their associated nanoparticles can bioaccumulate in in vitro and several in vivo organs, including the liver, intestine, and even in the brain. Severe intestinal damage and in ammation are also observed, the toxic effect of which is mostly pronounced from hydrolyzed oligomer products. Furthermore, the oligomers' potential protein target screening using large scale pharmacophore model reveals that oligomers can interact with matrix metallopeptidase 12 protein (MMP12), which is further validated using protein binding assay. A close mechanistic study reveals high binding a nity of oligomers to the catalytic zinc ion nger domain, leading to MMP12 inactivation and mediating the adverse bowel in ammatory effect following PLA oligomer exposure. Since biodegradable plastics are highly proposed as one solution for the global plastic problem, understanding the gastrointestinal fate and toxicity of bioplastics, will provide groundbreaking data on bioplastics as a substantial risk to human health.

Polylactic Acid Microplastics Do Not Exhibit Lower Biological Toxicity in Growing Mice Compared to Polyvinyl Chloride Microplastics

“…Nanoplastics and MPs with small particle sizes can even enter cells, directly interfering with intracellular lipid synthesis, transport, and metabolic homeostasis . Besides, the toxic oligomers released by PLA-MPs in the body were another vital factor for exacerbating the abnormalities of the digestive system and lipid metabolism in the body . Therefore, compared with conventional nondegradable MPs, PLA-MPs have the property that they can be partially degraded in the body, which will produce a large number of nanoparticles and toxic polymers, which will further enhance their toxicity in vivo. , …”

“…58 Besides, the toxic oligomers released by PLA-MPs in the body were another vital factor for exacerbating the abnormalities of the digestive system and lipid metabolism in the body. 59 Therefore, compared with conventional nondegradable MPs, PLA-MPs have the property that they can be partially degraded in the body, which will produce a large number of nanoparticles and toxic polymers, which will further enhance their toxicity in vivo. 59,60 PLAH Exposure Altered the Diversity and Composition of Fecal Microbiota.…”

Nanoplastics alter ecosystem multifunctionality and may increase global warming potential

“…Moreover, the distinct consequence of high doses and positively charged NPs on soil microbial community structure were clearer at the family level, wherein families with significantly higher relative abundance in PS‐N 3 treatment in NPs group was 1.8 and 2.7 times of that in PS‐N 0.3 and PS‐S 3 treatment, respectively (Figure 1d). Generally, small size plastic contaminants are widely perceived to exert their impacts on microorganisms in a dose‐dependent manner (Liu et al, 2021; Liu et al, 2023; Wang, Li, et al, 2023). Our observations indicate that the alterations of NPs on microbial communities were motivated by high doses and the positive surface charge of NPs.…”

“…The increasing plastic pollution is undoubtedly becoming a global problem (Borrelle et al, 2020; Stegmann et al, 2022). Owing to the poor management of plastic waste, the large plastic debris can be fragmented into microplastics (0.1 μm–5 mm) and nanoplastics (<0.1 μm) under the actions of mechanical abrasion, thermal/photo‐degradation, and biological degradation (Schiferle et al, 2023; Wang, Li, et al, 2023). Therefore, it is not surprising that microplastics (MPs) and nanoplastics (NPs) are detected in both urban and remote locations (Allen et al, 2022; Machado et al, 2018).…”

Oligomers and Monomers from Biodegradable Plastics: An Important but Neglected Threat to Ecosystems

“…To date, only sporadic studies have revealed the toxic effects of oligomers and monomers generated by BPs on organisms. In a mouse model, polylactic acid (PLA) nanoparticle oligomers were formed during gastrointestinal processes and bioaccumulated in the liver, intestine, and brain, causing intestinal damage and acute inflammation . Polycaprolactone (PCL) oligomers generated by hydrolysis inhibited the growth activity and nitrogen fixation of two cyanobacterial species .…”