Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

Abstract

Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

Synthesis and Physicochemical Transformations of Size‐Sorted Graphene Oxide during Simulated Digestion and Its Toxicological Assessment against an In Vitro Model of the Human Intestinal Epithelium

“…[57] In addition, food matrix effects have been shown to modulate the bioactivity of ENMs, [32,35] and the gut microbiome and proteome of animals is known to be sensitive to the presence of chemically active particulates. [28,29,60] Therefore, we plan to apply the methods developed here to interrogate the physicochemical transformations, toxicological assessment, and effect on gut microbiome and proteome of GO in the presence of more complex food models.…”

Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

“…Tissue-specific activity assay has demonstrated the important functions of DAF-16 in regulating longevity in the intestine and neurons of nematodes30. Interestingly, our previous study has suggested that mutation of sod-3 gene resulted in a susceptible property of nematodes to GO toxicity on lifespan, reproduction, and locomotion behavior, and induced a more severe induction of ROS production in GO exposed nematodes1921. In the present study, we employed an in vivo assay system of C. elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its potential molecular mechanisms.…”

“…Regarding the cellular mechanisms of GO toxicity, the published data have suggested that GO toxicity might be consequent to the bioavailability, induction of reactive oxygen species (ROS), enhanced intestinal permeability, disrupted innate immune response, and prolonged defecation cycle length in nematodes16171920. Previous studies have also implied the crucial role of intestinal biological barrier against GO toxicity in nematodes1721. It has also been reported that the induction of oxidative stress might play a key role in the chemical mechanism for GO induced shortened longevity in exposed nematodes15.…”

Wnt Ligands Differentially Regulate Toxicity and Translocation of Graphene Oxide through Different Mechanisms in Caenorhabditis elegans

“…To investigate the in vivo translocation and distribution of GO, Rho B was loaded on the GO by mixing Rho B solution (1 mg/mL, 0.3 mL) with aqueous GO suspension (0.1 mg/mL, 5 mL) as described58. The unbound Rho B was removed by dialysis against the distilled water over 72 h. The finally resulting GO/Rho B was stored at 4 °C.…”