Impact of microplastics on the human digestive system: From basic to clinical

Figure 1 Mechanism of the damage from microplastics to oral cavity. Microplastics induce oxidative stress, which triggers an inflammatory response, releasing inflammatory factors that damage the oral mucosa and increase microplastics absorption; and change the oral flora species and cause health problems. MPs: Microplastics; TNF: Tumor necrosis factor; IL: Interleukin.

Figure 2 How microplastics do harm to gastrointestine. Microplastics alter the gastrointestinal flora species and cause dysbiosis by changing the environment; reduce nutrient absorption and affect the growth of commensal flora; induce oxidative stress-mediated apoptosis of epithelial cells and increase permeability; act as a carrier to carry pathogens and plasticizers; and cause mechanical damage to the gastrointestinal tract. MPs: Microplastics; ROS: Reactive oxygen species; SOD: Superoxide dismutase; Nrf: Nuclear factor erythroid 2-related factor.

Figure 3 Mechanism of how microplastics influence lipid metabolism in liver. Microplastics up-regulate the expression of cytochrome P4502E1 and promote lipid peroxidation; down-regulate the expression of peroxisome proliferator-activated receptor and affect lipid metabolism; induce mitochondrial autophagy through the adenosine5’-monophosphate-activated protein kinase/UNC-51-like kinase pathway and affect energy supply; and carry fatty acids into the liver. MPs: Microplastics; CYP2E1: Cytochrome P4502E1; PPAR: Peroxisome proliferator-activated receptor; LPO: Lipid peroxides; AMPK: Adenosine5’-monophosphate-activated protein kinase; ULK1: UNC-51-like kinase; FA: Fatty acid; ATP: Adenosine triphosphate.

Figure 4 How microplastics act in the liver fibrosis. Microplastics enhance the expression of transforming growth factor-β and fibronectin, as well as the Wnt/β-catenin pathway and the cGAS/STING pathway to promote the progression of hepatic fibrosis; cirrhotic complications disrupt the intestinal barrier and increase the absorption of microplastics. MPs: Microplastics; TGF: Transforming growth factor.

Figure 5 Mechanism of the damage from microplastics to pancreatic cells. Microplastics induce oxidative stress causing oxidative damage; adsorb di(2-ethylhexyl) phthalate and act synergistically with it to promote oxidative stress in pancreatic intracellular endoplasmic reticulum and induce apoptosis in pancreatic cells; di(2-ethylhexyl) phthalate damage pancreatic β-cells’ DNA and reduce insulin secretion. MPs: Microplastics; ROS: Reactive oxygen species; DEHP: Di(2-ethylhexyl) phthalate.

Figure 6 The role that microplastics play in the cGAS/STING pathway. Microplastics induce oxidative stress, produce a large number of reactive oxygen species, damage DNA in the nucleus, and induce mitochondrial autopahgy. Damaged DNA enters the cytoplasm and interacts with double-stranded DNA sensor cGAS to catalyse guanosine triphosphate and adenosine triphosphate to form cyclic GMP-AMP. Cyclic GMP-AMP binds to STING homomeric diplosomes to activate downstream pathway and induce increased expression of transcription factors interferon regulatory factor 3 and phosphorylated nuclear factor-kappaB. Phosphorylated nuclear factor-kappaB, in turn, amplifies the action of the cGAS/STING signal. MPs: Microplastics; ROS: Reactive oxygen species; AMPK: Adenosine5’-monophosphate-activated protein kinase; ULK1: UNC-51-like kinase; IRF3: Interferon regulatory factor 3; p-NFκB: Phosphorylated nuclear factor-kappaB; cGAMP: Cyclic GMP-AMP; ATP: Adenosine triphosphate; GTP: Guanosine triphosphate.

Figure 7 Damage from the combination of microplastics and di(2-ethylhexyl) phthalate to pancreatic cells through glucose-regulating protein 78/C/EBP homologous protein/Bcl-2 pathway. The combination of di(2-ethylhexyl) phthalate and microplastics can induce oxidative stress and produce a large number of reactive oxygen species. Endoplasmic reticulum stress can be caused by various intracellular substances through reactive oxygen species. After stress, complexes formed by glucose-regulating protein 78, inositol-requiring enzyme 1, protein kinase RNA-like ER kinase, and activating transcription factor 6 on the endoplasmic reticulum can be disintegrated, thus promoting the activation of C/EBP homologous protein. Activation of C/EBP homologous protein can aggravate oxidative stress, but also promote the expression of apoptotic genes and induce apoptosis. MPs: Microplastics; SOD: Superoxide dismutase; DEHP: Di(2-ethylhexyl) phthalate; GSH: Glutathione; ROS: Reactive oxygen species; VEGF-A: Vascular endothelial growth factor A; ER: Endoplasmic reticulum; CHOP: C/EBP homologous protein; GRP78: Glucose-regulating protein 78; ATF6: Activating transcription factor 6; IRE1: Inositol-requiring enzyme 1; PERK: Protein kinase RNA-like ER kinase.