Porcine study reveals meurotoxic and pro-inflammatory effects of microplastics on enteric nervous system

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Jul 18 2024

A recent Nutrients study investigates the effects of polyethylene terephthalate (PET) microplastics on the neuronal population in the porcine jejunum.

Study: Oral Exposure to Microplastics Affects the Neurochemical Plasticity of Reactive Neurons in the Porcine Jejunum. Image Credit: SIVStockStudio / Shutterstock.com

Similarities between human and pig digestive systems

The jejunum is the middle part of the small intestine where food digestion and nutrient absorption occur. The enteric nervous system (ENS) regulates proper immune response, as well as enzyme and electrolyte secretion, within the jejunum.

The ENS is a dense network of nerve connections that are concentrated in two main plexuses including the myenteric plexus (Auerbach’s plexus-AP) and submucous plexus (Meissner’s plexus-MP). Auerbach’s plexus is present between the longitudinal and circular layers of smooth muscle along the entire length of the gastrointestinal (GI) tract, whereas Meissner’s plexus is located in the mucous membrane of the small and large intestine. Together, these plexuses regulate the motor and secretory functions of the GI tract.

MP is associated with the transfer of food content through the digestive tract. The intestinal muscle layers are relaxed and stimulated through different molecules. For example, the muscles of the GI tract are relaxed by inhibitory neurotransmitters, such as nitric oxide (NO), vasoactive intestinal peptide (VIP), purines, pituitary adenylate cyclase-activating peptide (PACAP), and stimulated by acetylcholine (ACh), galanin (GAL), or tachykinins like substance P-SP. Comparatively, epithelial secretory functions are regulated by the submucous plexus neurons.

The association between the ENS and digestive tract in pigs is similar to that of humans. Here, the submucous plexus can be divided into the inner submucous plexus (ISP) and outer submucous plexus (OSP). VIP and ACh are key neurotransmitters of the secretomotor neurons of this plexus, and NO exhibits inhibitory activities.

Human and pig exposure to plastics

Many plastics penetrate the natural environment by forming nano- and microplastics through chemical and physical processes. One study has shown that about 480 million particles can be formed from a single half-liter PET bottle.

Continual and long-term exposure to these nano- and microplastic fragments can negatively affect the environment and all living organisms. An individual can be exposed to microplastics through dermal, inhalation, and oral routes.

The presence of microplastics in humans has been confirmed in the placenta, breast milk, feces, lungs, blood, spleen, sputum, and bronchoalveolar fluid. Pigs are also exposed to microplastics through their feed, which may be stored in plastic containers or plastic bags.

About the study

The current study selected polyethylene terephthalate (MP-PET) for its experiments because it is commonly used in the food industry for packaging food and beverages.

A total of 15 sexually immature pigs that were eight weeks old were selected for this study. At the acclimatization stage, pigs were fed twice with commercial feed and had access to water ad libitum.

Pigs were then randomly divided into control, low-dose (LD), or high-dose (HD) groups. For 28 days, the LD and HD groups received 0.1 g of MP-PET/day/animal and one g of MP-PET/day/animal, respectively. Microplastics were orally administered using a capsule applicator once daily. The control group received empty capsules.

After 28 days of treatment, animals were euthanized following standard protocol, and tissue samples, including an eight cm section of the jejunum, were collected for histological examinations.

Study findings

Under normal physiological conditions, neuronal nitric oxide synthase (nNOS)-positive neurons were most abundantly found in the control samples. However, this abundance was significantly reduced in the HD group. A significant reduction in cholinergic neurons in HD and LD groups was also observed.

LD and HD MP-PET exposure reduced the population of cocaine- and amphetamine-regulated transcript (CART)-positive neurons. An increase in the neuronal population was only found for galanin (GAL). As compared to the submucous plexuses, MP exhibited a reduction in the percentage of SP-positive neurons.

This neurotoxicity may be due to altered neurotransmitter levels, microplastic accumulation in the mitochondria causing its dysfunction, direct physical damage, induction of oxidative stress, or disruption of the gut microbiome. Microplastic accumulation also triggers the expression of pro-apoptotic proteins such as caspase 3, bcl-2-like protein 4 (BAX), and cytochrome c, as well as the production of pro-inflammatory cytokines like interleukin 8 (IL-8), nuclear factor κB (NF-κB), and tumor necrosis factor α (TNF-α).

Throughout the study period, no changes in behavior, appetite, onset of diarrhea, or growth inhibition were observed in any pigs.

Conclusions

The current study indicated that oral exposure to microplastics influences ENS function through potential neurotoxic and pro-inflammatory pathways. Although additional research is needed to elucidate the exact mechanisms involved this process, the study findings suggest that GAL and SP may induce inflammation in the ENS of the porcine jejunum.