Abstract
Microplastics (MPs) are known to cause liver toxicity as they can spread through the food chain. Most researches on their toxicity have focused on individual organs, neglecting the crucial “gut-liver axis”—a bidirectional communication pathway between the gut and liver. Probiotics have shown promise in modulating the effects of environmental pollutants. In this study, we exposed mice to Lactobacillus rhamnosus GG (LGG, 100 mg/kg b.w./d) and/or polystyrene microplastics (PS-MPs, 5 mg/kg b.w./d) for 28 d via gavage to investigate how probiotics influence live toxicity through the gut-liver axis. Our results demonstrated that PS-MPs induced liver inflammation (increased IL-6 and TNF-α) and disrupted lipid metabolism. However, when combined with LGG, these effects were alleviated. LGG also improved colon health, rectifying ciliary defects and abnormal mucus secretion caused by PS-MPs. Furthermore, LGG improved gut microbiota dysbiosis induced by PS-MPs. Metabolomics and gene expression analysis (Cyp7a1 and Cyp7b1) indicated that LGG modulated bile acid metabolism. In summary, LGG appears to protect the liver by maintaining gut homeostasis, enhancing gut barrier integrity, and reducing the liver inflammation. These findings confirm the potential of LGG to modulate liver toxicity caused by PS-MPs through the gut-liver axis, offering insights into probiotics' application for environmental pollutant detoxification.
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Abbreviations
- MPs:
-
microplastics
- PS-MPs:
-
polystyrene microplastics
- TEM:
-
transmission electron microscopy
- LGG:
-
Lactobacillus rhamnosus GG
- SPF:
-
specific pathogen-free
- DW:
-
distilled water
- H&E:
-
Hematoxylin-eosin
- AB-PAS:
-
Alcian Blue-Periodic Acid Schiff
- PBS:
-
phosphate buffered saline
- TP:
-
total protein
- BCA:
-
bicinchoninic acid
- ALT:
-
alanine aminotransferase
- AST:
-
aspartate aminotransferase
- SOD:
-
superoxide dismutase
- GSH-PX:
-
glutathione peroxidase
- LPS:
-
lipopolysaccharide
- ELISA:
-
enzyme-linked immunosorbent assay
- qRT-PCR:
-
quantitative real-time polymerase chain reaction
- OTUs:
-
operational taxonomic units
- PLS-DA:
-
partialleast squares discriminant analysis
- UPGMA:
-
unweighted pair-group method with arithmetic mean
- LDA:
-
Linear discriminant analysis
- LEfse:
-
linear discriminant analysis effect size
- UPLC-Q-TOF-MS:
-
ultra performance liquid chromatography- quadrupole-time of flight- mass spectrometer
- QC:
-
quality control
- KEGG:
-
the Kyoto Encylopaedia of Genes and Genomes
- HMDB:
-
the Human Metabolome Database
- OPLS-DA:
-
orthogonal partial least-squares discrimination analysis
- FC:
-
fold change
- VIP:
-
variable importance in projection
- SCMs:
-
significantly changed metabolites
- SD:
-
standard deviations
- ANOVA:
-
a one-way analysis of variance
- Keap1-Nrf2/ARE:
-
kelch-like ECH associated protein 1- nuclear factor-erythroid-2-related factor 2/ antioxidant response element
- SCFAs:
-
short-chain fatty acids
- TNF-α:
-
tumor necrosis factor-α
- IL-6:
-
interleukin-6
- Cyp7a1:
-
cytochrome P450 family 7 subfamily A member 1
- Cyp7b1:
-
cytochrome P450 family 7 subfamily B member 1
References
Arellano-Garcia L, Trepiana J, Martinez JA, Portillo MP, Milton-Laskibar I (2023) Beneficial effects of viable and heat-inactivated Lactobacillus rhamnosus GG administration on oxidative stress and inflammation in diet-induced NAFLD in rats. Antioxidants 12(3):717. https://doi.org/10.3390/antiox12030717
Bazeli J, Banikazemi Z, Hamblin MR, Chaleshtori RS (2023) Could probiotics protect against human toxicity caused by polystyrene nanoplastics and microplastics? Front Nutr 10:1186724. https://doi.org/10.3389/fnut.2023.1186724
Berger K, Burleigh S, Lindahl M, Bhattacharya A, Patil P, Stalbrand H, Nordberg KE, Hallenius F, Nyman M, Adlercreutz P (2021) Xylooligosaccharides increase Bifidobacteria and Lachnospiraceae in mice on a high-fat diet, with a concomitant increase in short-chain fatty acids, especially butyric acid. J Agric Food Chem 69(12):3617–3625. https://doi.org/10.1021/acs.jafc.0c06279
Bhutto SU, You XY (2022) Spatial distribution of microplastics in Chinese freshwater ecosystem and impacts on food webs*. Environ Pollut 293:118494. https://doi.org/10.1016/j.envpol.2021.118494
Bonanomi M, Salmistraro N, Porro D, Pinsino A, Colangelo AM, Gaglio D (2022) Polystyrene micro and nano-particles induce metabolic rewiring in normal human colon cells: A risk factor for human health. Chemosphere 303(Pt 1):134947. https://doi.org/10.1016/j.chemosphere.2022.134947
Cassidy K, Elyashiv-Barad S (2007) US FDA’s revised consumption factor for polystyrene used in food-contact applications. Food Addit Contam 24(9):1026–1031. https://doi.org/10.1080/02652030701313797
Chen L, Lam JCW, Tang L, Hu C, Liu M, Lam PKS, Zhou B (2020) Probiotic modulation of lipid metabolism disorders caused by perfluorobutanesulfonate pollution in zebrafish. Environ Sci Technol 54(12):7494–7503. https://doi.org/10.1021/acs.est.0c02345
Ding Y, Yan Y, Chen D, Ran L, Mi J, Lu L, Jing B, Li X, Zeng X, Cao Y (2019) Modulating effects of polysaccharides from the fruits of Lycium barbarum on the immune response and gut microbiota in cyclophosphamide-treated mice. Food Funct 10(6):3671–3683. https://doi.org/10.1039/c9fo00638a
Dong R, Zhou C, Wang S, Yan Y, Jiang Q (2022) Probiotics ameliorate polyethylene microplastics-induced liver injury by inhibition of oxidative stress in Nile tilapia (Oreochromis niloticus). Fish Shellfish Immunol 130:261–272. https://doi.org/10.1016/j.fsi.2022.09.022
Dou C, Shang Z, Qiao J, Wang Y, Li H (2021) Clostridium butyricum protects IPEC-J2 cells from ETEC K88-induced oxidative damage by activating the Nrf2/ARE signaling pathway. Oxid Med Cell Longev 2021:4464002. https://doi.org/10.1155/2021/4464002
Evangelakos I, Heeren J, Verkade E, Kuipers F (2021) Role of bile acids in inflammatory liver diseases. Semin Immunopathol 43(4):577–590. https://doi.org/10.1007/s00281-021-00869-6
Geng Y, Zhang Z, Zhou W, Shao X, Li Z, Zhou Y (2023) Individual exposure to microplastics through the inhalation route: Comparison of microplastics in inhaled indoor aerosol and exhaled breath air. Environmental Science & Technology Letters 10(6):464–470. https://doi.org/10.1021/acs.estlett.3c00147
Greenblum S, Turnbaugh PJ, Borenstein E (2012) Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease. Proc Natl Acad Sci USA 109(2):594–599. https://doi.org/10.1073/pnas.1116053109
Gruszewska E, Cylwik B, Gudowska M, Panasiuk A, Flisiak R, Chrostek L (2019) The concentration of total sialic acid in chronic hepatitis B and C. Ann Clin Biochem 56(1):118–122. https://doi.org/10.1177/0004563218792292
Holmes E, Li JV, Athanasiou T, Ashrafian H, Nicholson JK (2011) Understanding the role of gut microbiome-host metabolic signal disruption in health and disease. Trends Microbiol 19(7):349–359. https://doi.org/10.1016/j.tim.2011.05.006
Hong Y, Wu S, Wei G (2023) Adverse effects of microplastics and nanoplastics on the reproductive system: A comprehensive review of fertility and potential harmful interactions. Sci Total Environ 903:166258. https://doi.org/10.1016/j.scitotenv.2023.166258
Horvatits T, Tamminga M, Liu B, Sebode M, Carambia A, Fischer L, Puschel K, Huber S, Fischer EK (2022) Microplastics detected in cirrhotic liver tissue. EBioMedicine 82:104147. https://doi.org/10.1016/j.ebiom.2022.104147
Hu C, Liu M, Wan T, Tang L, Sun B, Zhou B, Lam JCW, Lam PKS, Chen L (2021) Disturbances in Microbial and Metabolic Communication across the Gut-Liver Axis Induced by a Dioxin-like Pollutant: An Integrated Metagenomics and Metabolomics Analysis. Environ Sci Technol 55(1):529–537. https://doi.org/10.1021/acs.est.0c06884
Jin Y, Wu S, Zeng Z, Fu Z (2017) Effects of environmental pollutants on gut microbiota. Environ Pollut 222:1–9. https://doi.org/10.1016/j.envpol.2016.11.045
Kalhan SC, Edmison J, Marczewski S, Dasarathy S, Gruca LL, Bennett C, Duenas C, Lopez R (2011) Methionine and protein metabolism in non-alcoholic steatohepatitis: evidence for lower rate of transmethylation of methionine. Clin Sci 121(4):179–189. https://doi.org/10.1042/CS20110060
Kang DJ, Betrapally NS, Ghosh SA, Sartor RB, Hylemon PB, Gillevet PM, Sanyal AJ, Heuman DM, Carl D, Zhou H, Liu R, Wang X, Yang J, Jiao C, Herzog J, Lippman HR, Sikaroodi M, Brown RR, Bajaj JS (2016) Gut microbiota drive the development of neuroinflammatory response in cirrhosis in mice. Hepatology 64(4):1232–1248. https://doi.org/10.1002/hep.28696
Konturek PC, Harsch IA, Konturek K, Schink M, Konturek T, Neurath MF, Zopf Y (2018) Gut-liver axis: How do gut bacteria influence the liver? Med Sci 6(3):79. https://doi.org/10.3390/medsci6030079
Korpela K, Mutanen A, Salonen A, Savilahti E, de Vos WM, Pakarinen MP (2017) Intestinal microbiota signatures associated with histological liver steatosis in pediatric-onset intestinal failure. J Parenter Enteral Nutr 41(2):238–248. https://doi.org/10.1177/0148607115584388
Li A, Wang Y, Kulyar MF, Iqbal M, Lai R, Zhu H, Li K (2023) Environmental microplastics exposure decreases antioxidant ability, perturbs gut microbial homeostasis and metabolism in chicken. Sci Total Environ 856(Pt 1):159089. https://doi.org/10.1016/j.scitotenv.2022.159089
Lin P, Guo Y, He L, Liao X, Chen X, He L, Lu Z, Qian ZJ, Zhou C, Hong P, Sun S, Li C (2021) Nanoplastics aggravate the toxicity of arsenic to AGS cells by disrupting ABC transporter and cytoskeleton. Ecotoxicol Environ Saf 227:112885. https://doi.org/10.1016/j.ecoenv.2021.112885
Liu TH, Wang J, Zhang CY, Zhao L, Sheng YY, Tao GS, Xue YZ (2023) Gut microbial characteristical comparison reveals potential anti-aging function of Dubosiella newyorkensis in mice. Front Endocrinol 14:1133167. https://doi.org/10.3389/fendo.2023.1133167
Ma J, Gong S, He Y, Gao W, Hao W, Lan X (2021) Effects of oral sialic acid on gut development, liver function and gut microbiota in mice. Lett Appl Microbiol 73(1):20–25. https://doi.org/10.1111/lam.13447
Machate DJ, Figueiredo PS, Marcelino G, Guimarães RCA, Hiane PA, Bogo D, Pinheiro VAZ, Oliveira LCS, Pott A (2020) Fatty acid diets: Regulation of gut microbiota composition and obesity and its related metabolic dysbiosis. Int J Mol Sci 21(11):4093. https://doi.org/10.3390/ijms21114093
Mamun AA, Prasetya TAE, Dewi IR, Ahmad M (2023) Microplastics in human food chains: Food becoming a threat to health safety. Sci Total Environ 858(Pt 1):159834. https://doi.org/10.1016/j.scitotenv.2022.159834
Mu YW, Sun JY, Li ZY, Zhang WX, Liu ZD, Li C, Peng C, Cui GQ, Shao H, Du ZJ (2022) Activation of pyroptosis and ferroptosis is involved in the hepatotoxicity induced by polystyrene microplastics in mice. Chemosphere 291:132944. https://doi.org/10.1016/j.chemosphere.2021.132944
Mukherjee A, Lordan C, Ross RP, Cotter PD (2020) Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health. Gut Microbes 12(1):1802866. https://doi.org/10.1080/19490976.2020.1802866
Piao Y, Liu Y, Xie X (2013) Change trends of organ weight background data in sprague dawley rats at different ages. J Toxicol Pathol 26(1):29–34. https://doi.org/10.1293/tox.26.29
Ren S, Marques D, Redford K, Hylemon PB, Gil G, Vlahcevic ZR, Pandak WM (2003) Regulation of oxysterol 7alpha-hydroxylase (CYP7B1) in the rat. Metabolism 52(5):636–642. https://doi.org/10.1053/meta.2003.50106
Senathirajah K, Attwood S, Bhagwat G, Carbery M, Wilson S, Palanisami T (2021) Estimation of the mass of microplastics ingested - A pivotal first step towards human health risk assessment. J Hazard Mater 404:124004. https://doi.org/10.1016/j.jhazmat.2020.124004
Sharma V, Anderson D, Dhawan A (2012) Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis 17(8):852–870. https://doi.org/10.1007/s10495-012-0705-6
Shen R, Yang K, Cheng X, Guo C, Xing X, Sun H, Liu D, Liu X, Wang D (2022) Accumulation of polystyrene microplastics induces liver fibrosis by activating cGAS/STING pathway. Environ Pollut 300:118986. https://doi.org/10.1016/j.envpol.2022.118986
Shen X, Liang X, Ji X, You J, Zhuang X, Song Y, Yin H, Zhao M, Zhao L (2021) CD36 and DGAT2 facilitate the lipid-lowering effect of chitooligosaccharides via fatty acid intake and triglyceride synthesis signaling. Food Funct 12(18):8681–8693. https://doi.org/10.1039/d1fo01472b
Shi C, Han X, Guo W, Wu Q, Yang X, Wang Y, Tang G, Wang S, Wang Z, Liu Y, Li M, Lv M, Guo Y, Li Z, Li J, Shi J, Qu G, Jiang G (2022) Disturbed gut-liver axis indicating oral exposure to polystyrene microplastic potentially increases the risk of insulin resistance. Environ Int 164:107273. https://doi.org/10.1016/j.envint.2022.107273
Sonnenburg ED, Zheng H, Joglekar P, Higginbottom SK, Firbank SJ, Bolam DN, Sonnenburg JL (2010) Specificity of polysaccharide use in intestinal bacteroides species determines diet-induced microbiota alterations. Cell 141(7):1241–1252. https://doi.org/10.1016/j.cell.2010.05.005
Sun W, Yan S, Meng Z, Tian S, Jia M, Huang S, Wang Y, Zhou Z, Diao J, Zhu W (2022a) Combined ingestion of polystyrene microplastics and epoxiconazole increases health risk to mice: Based on their synergistic bioaccumulation in vivo. Environ Int 166:107391. https://doi.org/10.1016/j.envint.2022.107391
Sun Y, Zhang S, Nie Q, He H, Tan H, Geng F, Ji H, Hu J, Nie S (2022b) Gut firmicutes: Relationship with dietary fiber and role in host homeostasis. Crit Rev Food Sci Nutr 1-16. https://doi.org/10.1080/10408398.2022.2098249
Surana NK, Kasper DL (2017) Moving beyond microbiome-wide associations to causal microbe identification. Nature 552(7684):244–247. https://doi.org/10.1038/nature25019
Tao J, Deng P, Lin M, Chen C, Ma Q, Yang L, Zhang W, Luo Y, Chen S, Pi H, Zhou Z, Yu Z (2023) Long-term exposure to polystyrene microplastics induces hepatotoxicity by altering lipid signatures in C57BL/6J mice. Chemosphere 347:140716. https://doi.org/10.1016/j.chemosphere.2023.140716
Thompson RC, Olsen Y, Mitchell RP, Davis A, Rowland SJ, John AWG, McGonigle D, Russell AE (2004) Lost at sea: Where is all the plastic? Science 304(5672):838–838. https://doi.org/10.1126/science.1094559
Wan F, Han H, Zhong R, Wang M, Tang S, Zhang S, Hou F, Yi B, Zhang H (2021) Dihydroquercetin supplement alleviates colonic inflammation potentially through improved gut microbiota community in mice. Food Funct 12(22):11420–11434. https://doi.org/10.1039/d1fo01422f
Wang L, Chen J, Zhang X, Xu M, Zhang X, Zhao W, Cui J (2023a) Effects of microplastics and tetracycline on intestinal injury in mice. Chemosphere 337:139364. https://doi.org/10.1016/j.chemosphere.2023.139364
Wang S, Wu H, Shi X, Wang Y, Xu S (2023c) Polystyrene microplastics with different sizes induce the apoptosis and necroptosis in liver through the PTEN/PI3K/AKT/autophagy axis. Sci Total Environ 899:165461. https://doi.org/10.1016/j.scitotenv.2023.165461
Wang X, Wang Z, Cao J, Dong Y, Chen Y (2023b) Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation. Microbiome 11(1):17. https://doi.org/10.1186/s40168-022-01452-3
Wlcek K, Stieger B (2014) ATP-binding cassette transporters in liver. Biofactors 40(2):188–198. https://doi.org/10.1002/biof.1136
Yang JZ, Zhang KK, Liu Y, Li XW, Chen LJ, Liu JL, Li JH, Chen L, Hsu C, Zeng JH, Xie XL, Wang Q (2023b) Epigallocatechin-3-gallate ameliorates polystyrene microplastics-induced anxiety-like behavior in mice by modulating gut microbe homeostasis. Sci Total Environ 892:164619. https://doi.org/10.1016/j.scitotenv.2023.164619
Yang Q, Liang Q, Balakrishnan B, Belobrajdic DP, Feng QJ, Zhang W (2020) Role of dietary nutrients in the modulation of gut microbiota: A narrative review. Nutrients 12(2):381. https://doi.org/10.3390/nu12020381
Yang Y, Yu J, Huo J, Yan Y (2023a) Sesamolin Attenuates Kidney Injury, Intestinal barrier dysfunction, and gut microbiota imbalance in high-fat and high-fructose diet-fed mice. J Agric Food Chem 71(3):1562–1576. https://doi.org/10.1021/acs.jafc.2c07084
Ye J, Zhao Y, Chen X, Zhou H, Yang Y, Zhang X, Huang Y, Zhang N, Lui EMK, Xiao M (2021) Pu-erh tea ameliorates obesity and modulates gut microbiota in high fat diet fed mice. Food Res Int 144:110360. https://doi.org/10.1016/j.foodres.2021.110360
Yin K, Wang D, Zhang Y, Lu H, Hou L, Guo T, Zhao H, Xing M (2023) Polystyrene microplastics promote liver inflammation by inducing the formation of macrophages extracellular traps. J Hazard Mater 452:131236. https://doi.org/10.1016/j.jhazmat.2023.131236
Yin K, Wang D, Zhang Y, Lu H, Wang Y, Xing M (2022) Dose-effect of polystyrene microplastics on digestive toxicity in chickens (Gallus gallus): Multi-omics reveals critical role of gut-liver axis. J Adv Res 52:3–18. https://doi.org/10.1016/j.jare.2022.10.015
Yu J, Chen L, Wu B (2023) Size-specific effects of microplastics and lead on zebrafish. Chemosphere 337:139383. https://doi.org/10.1016/j.chemosphere.2023.139383
Zhang K, Zhu L, Zhong Y, Xu L, Lang C, Chen J, Yan F, Li J, Qiu J, Chen Y, Sun D, Wang G, Qu K, Qin X, Wu W (2023b) Prodrug integrated envelope on probiotics to enhance target therapy for ulcerative colitis. Adv Sci 10(4):e2205422. https://doi.org/10.1002/advs.202205422
Zhang Y, Hou B, Liu T, Wu Y, Wang Z (2023a) Probiotics improve polystyrene microplastics-induced male reproductive toxicity in mice by alleviating inflammatory response. Ecotoxicol Environ Saf 263:115248. https://doi.org/10.1016/j.ecoenv.2023.115248
Zhao L, Shi W, Hu F, Song X, Cheng Z, Zhou J (2021) Prolonged oral ingestion of microplastics induced inflammation in the liver tissues of C57BL/6J mice through polarization of macrophages and increased infiltration of natural killer cells. Ecotoxicol Environ Saf 227:112882. https://doi.org/10.1016/j.ecoenv.2021.112882
Zheng H, Wang J, Wei X, Chang L, Liu S (2021) Proinflammatory properties and lipid disturbance of polystyrene microplastics in the livers of mice with acute colitis. Sci Total Environ 750:143085. https://doi.org/10.1016/j.scitotenv.2020.143085
Zhong X, Zhao Y, Huang L, Liu J, Wang K, Gao X, Zhao X, Wang X (2023) Remodeling of the gut microbiome by Lactobacillus johnsonii alleviates the development of acute myocardial infarction. Front Microbiol 14:1140498. https://doi.org/10.3389/fmicb.2023.1140498
Funding
This study was supported by the National Natural Science Foundation of China (22306100) and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (NO. 23KJB610012).
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Changhao Yu: Validation, Formal analysis, Investigation, Writing - original draft. Yawen Xu: Methodology, Investigation. Yiping Wei: Methodology, Investigation. Yuxue Guo: Investigation. Yi Wang: Investigation. Ping Song: Methodology, Supervision. Jing Yu: Conceptualization, Methodology, Software, Writing - review & editing, Funding acquisition, Project administration.
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Yu, C., Xu, Y., Wei, Y. et al. Gut microbiota and liver metabolomics reveal the potential mechanism of Lactobacillus rhamnosus GG modulating the liver toxicity caused by polystyrene microplastics in mice. Environ Sci Pollut Res 31, 6527–6542 (2024). https://doi.org/10.1007/s11356-023-31564-8
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DOI: https://doi.org/10.1007/s11356-023-31564-8