Fluoride Action Network

Abstract

Intestinal microflora plays a key role in maintaining the homeostasis between immune and host health. Here, we reported the fluoride-induced changes of rectal structure and microflora in mice. The morphology of rectal tissue was observed by hematoxylin and eosin staining. The rectal development parameters (the thickness of mucosa, intestinal gland and muscle layer) were evaluated. The proliferation of rectal epithelial cells was evaluated via BrdU labeling. The distribution of goblet, glycoprotein and mast cell were evaluated by specific staining. Rectal microflora was detected using 16S rRNA high-throughput sequencing. The results showed that the rectal structure was seriously damaged and the proliferation of rectal epithelial cells was significantly inhibited by fluoride. The distribution of goblet cells, glycoprotein and mast cells decreased significantly after fluoride exposure. The relative richness of microfloras was changed after fluoride treatment, such as increased Bacteroidetes and decreased Firmicutes. In summary, this study indicated that excessive fluoride damages the intestinal structure, disturbs the intestinal micro-ecology and causes intestinal microflora disorder in mice. Findings mentioned in the present study enrich a new scope for elucidating fluoride toxicity from intestinal homeostasis.

Original abstract online at https://link.springer.com/article/10.1007%2Fs11356-019-07201-8

References

Abdelqader A, Al-Fataftah AR, Da? G (2013) Effects of dietary Bacillus subtilis and inulin supplementation on performance, eggshell quality, intestinal morphology and microflora composition of laying hens in the late phase of production. Anim Feed Sci Technol 179(1-4):103–111. https://doi.org/10.1016/j.anifeedsci.2012.11.003

Apas AL, Arena ME, Colombo S, Gonzalez SN (2015) Probiotic administration modifies the milk fatty acid profile, intestinal morphology, and intestinal fatty acid profile of goats. J Dairy Sci 98(1):47–54. https://doi.org/10.3168/jds.2013-7805

Arabestani MR, Rajabpour M, Yousefi Mashouf R, Alikhani MY, Mousavi SM (2015) Expression of efflux pump MexAB-OprM and OprD of Pseudomonas aeruginosa strains isolated from clinical samples using qRT-PCR. Arch Iran Med 18(2):102–108

Arumugam M, Raes J, Pelletier E et al (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174. https://doi.org/10.1038/nature09944

Bili?-Šobot D, Kubale V, Škrlep M, ?andek-Potokar M, Prevolnik Povše M, Fazarinc G, Škorjanc D (2016) Effect of hydrolysable tannins on intestinal morphology, proliferation and apoptosis in entire male pigs. Arch Anim Nutr 70(5):378–388. https://doi.org/10.1016/10.1080/1745039X.2016.1206735

Bautil A, Verspreet J, Buyse J, Goos P, Bedford MR, Courtin CM (2019) Age-related arabinoxylan hydrolysis and fermentation in the gastrointestinal tract of broilers fed wheat-based diets. Poult Sci. https://doi.org/10.3382/ps/pez159

Bhatia S, Prabhu PN, Benefiel AC, Miller MJ, Chow J, Davis SR, Gaskins HR (2015) Galacto-oligosaccharides may directly enhance intestinal barrier function through the modulation of goblet cells. Mol Nutr Food Res 59(3):566–573. https://doi.org/10.1002/mnfr.201400639

Chen L, Zhang M, Li H, Tang S, Fu X (2014) Distribution of BrdU label-retaining cells in eccrine sweat glands and comparison of the percentage of BrdU-positive cells in eccrine sweat glands and in epidermis in rats. Arch Dermatol Res 306(2):157–162. https://doi.org/10.1007/s00403-013-1397-7

Chakravorty S, Helb D, Burday M, Connell N, Alland D (2007) A detailed analysis of 16S ribosomal RNA gene segments for the diagnosis of pathogenic bacteria. J Microbiol Methods 69(2):330–339. https://doi.org/10.1016/j.mimet.2007.02.005

Chauhan SS, Mahmood A, Ojha S (2013) Ethanol and age enhances fluoride toxicity through oxidative stress and mitochondrial dysfunctions in rat intestine. Mol Cell Biochem 384(1-2):251–262. https://doi.org/10.1007/s11010-013-1804-6

Chauhan SS, Ojha S, Mahmood A (2011) Modulation of lipid peroxidation and antioxidant defense systems in rat intestine by subchronic fluoride and ethanol administration. Alcohol 45(7):663–672. https://doi.org/10.1016/j.alcohol.2010.10.008

De la Fuente B, Vázquez M, Rocha RA, Devesa V, Vélez D (2016) Effects of sodium fluoride on immune response in murine macrophages. Toxicol in Vitro 34:81–87. https://doi.org/10.1016/j.tiv.2016.03.001

Dec K, Lukomska A, Maciejewska D, Jakubczyk K, Baranowska-Bosiacka I, W?sik A, Chlubek D, Gutowska I (2017) The influence of fluorine on the disturbances of homeostasis in the central nervous system. Biol Trace Elem Res 177(2):224–234. https://doi.org/10.1016/10.1007/s12011-016-0871-4

Díaz-Rizzolo DA, Kostov B, López-Siles M, Serra A, Colungo C, González-de-Paz L, Martinez-Medina M, Siso-Almirall A, Gomis R (2019) Healthy dietary pattern and their corresponding gut microbiota profile are linked to a lower risk of type 2 diabetes, independent of the presence of obesity. Clin Nutr. https://doi.org/10.1016/j.clnu.2019.02.035

Ge J, Zhang C, Sun YC, Zhang Q, Lv MW, Guo K, Li JL (2019) Cadmium exposure triggers mitochondrial dysfunction and oxidative stress in chicken (Gallus gallus) kidney via mitochondrial UPR inhibition and Nrf2-mediated antioxidant defense activation. Sci Total Environ 689:1160–1171. https://doi.org/10.1016/j.scitotenv.2019.06.405

Gerritsen J, Smidt H, Rijkers GT, de Vos WM (2011) Intestinal microbiota in human health and disease: the impact of probiotics. Genes Nutr 6(3):209. https://doi.org/10.1007/s12263-011-0229-7

Islam M, Mishra PC, Patel R (2011) Fluoride adsorption from aqueous solution by a hybrid thorium phosphate composite. Chem Eng J 166(3):978–985. https://doi.org/10.1016/j.cej.2010.11.087

Jin C, Peng K, Liu T, Wang L, Cao W, Song H, Liu H (2013) Distribution law of goblet cells in the intestinal tracts of African ostrich chicks. Agric Sci Technol 14(1):103. https://doi.org/10.1186/s12917-018-1690-y

Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC (2008) The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci 105(39):15064–15069. https://doi.org/10.1073/pnas.0803124105

Kojima A, Nakano K, Wada K et al (2012) Infection of specific strains of Streptococcus mutans, oral bacteria, confers a risk of ulcerative colitis. Sci Rep 2:332. https://doi.org/10.1038/srep00332

Kim YS, Ho SB (2010) Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep 12(5):319–330. https://doi.org/10.1007/s11894-010-0131-2

Kamada N, Núñez G (2014) Regulation of the immune system by the resident intestinal bacteria. Gastroenterology 146(6):1477–1488. https://doi.org/10.1053/j.gastro.2014.01.060

Lambert GP (2009) Stress-induced gastrointestinal barrier dysfunction and its inflammatory effects. J Anim Sci 7(suppl_14):101–E108. https://doi.org/10.2527/jas.2008-1339

Luo Q, Cui HM, Peng X, Fang J, Zuo ZC, Deng JL, Liu J, Deng YB (2013) Intestinal IgA+ cell numbers as well as IgA, IgG, and IgM contents correlate with mucosal humoral immunity of broilers during supplementation with high fluorine in the diets. Biol Trace Elem Res 154(1):62–72. https://doi.org/10.1007/s12011-013-9713-9

Lynch SV, Pedersen O (2016) The human intestinal microbiome in health and disease. N Engl J Med 375(24):2369–2379. https://doi.org/10.1056/NEJMra1600266

Liu J, Wang HW, Lin L, Miao CY, Zhang Y, Zhou BH (2019) Intestinal barrier damage involved in intestinal microflora changes in fluoride-induced mice. Chemosphere. https://doi.org/10.1016/j.chemosphere.2019.06.080

Liao Y, Chen J, Brandt BW, Zhu Y, Li J, van Loveren C, Deng DM (2015) Identification and functional analysis of genome mutations in a fluoride-resistant Streptococcus mutans strain. PLoS One 10(4):e0122630. https://doi.org/10.1371/journal.pone.0122630

Li GN, Xia XJ, Tang WC, Zhu Y (2016) Intestinal microecology associated with fluoride resistance capability of the silkworm (Bombyx mori L.). Appl Microbiol Biotechnol 100(15):6715–6724. https://doi.org/10.1007/s00253-016-7480-1

Lan A, Andriamihaja M, Blouin JM, Liu X, Descatoire V, de Maredsous CD, Davilaa AM, Walkerb F, Toméa D, Blachier F (2015) High-protein diet differently modifies intestinal goblet cell characteristics and mucosal cytokine expression in ileum and colon. J Nutr Biochem 26(1):91–98. https://doi.org/10.1016/j.jnutbio.2014.09.007

Lin J, Zhao HS, Qin L, Li XN, Zhang C, Xia J, Li JL (2018) Atrazine triggers mitochondrial dysfunction and oxidative stress in quail (Coturnix C. coturnix) cerebrum via activating xenobiotic-sensing nuclear receptors and modulating cytochrome P450 systems. J Agric Food Chem 66(25):6402–6413. https://doi.org/10.1021/acs.jafc.8b01413

Luo Q, Cui H, Peng X, Fang J, Zuo Z, Deng J, Liu J, Deng Y (2016) Dietary high fluorine alters intestinal microbiota in broiler chickens. Biol Trace Elem Res 173(2):483–491. https://doi.org/10.1007/s12011-016-0672-9

Osho SO, Wang T, Horn NL, Adeola O (2017) Comparison of goblet cell staining methods in jejunal mucosa of Turkey poults. Poult Sci 96(3):556–559. https://doi.org/10.3382/ps/pew324

Ohkusa T, Koido S (2015) Intestinal microbiota and ulcerative colitis. J Infect Chemother 21(11):761–768. https://doi.org/10.1016/j.jiac.2015.07.010

Parvez S, Malik KA, Ah Kang S, Kim HY (2006) Probiotics and their fermented food products are beneficial for health. J Appl Microbiol 100(6):1171–1185. https://doi.org/10.1111/j.1365-2672.2006.02963.x

Sartor RB (2008) Microbial influences in inflammatory bowel diseases. Gastroenterology 134(2):577–594. https://doi.org/10.1053/j.gastro.2007.11.059

Shi J, Wang Y, He J et al (2017) Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model. FASEB J 31(8):3695–3709. https://doi.org/10.1096/fj.201700034R

Schwarzer M, Hermanova P, Srutkova D, Golias J, Hudcovic T, Sinkora M, Zwicker C, Wiedermann U, Tuckova L, Kozakova H, Schabussova I (2019) Germ-free mice exhibit mast cells with impaired functionality and gut homing and do not develop food allergy. Front Immunol 10:205. https://doi.org/10.3389/fimmu.2019.00205

Sartor RB, Wu GD (2017) Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology 152(2):327–339. https://doi.org/10.1053/j.gastro.2016.10.012

Tang W, Zheng X, Li D, Xiao Y, Yang C, Shang S, Shi M, Zhu Y (2018) Effects of sodium fluoride on the reproductive development of Bombyx mori. Environ Toxicol Pharmacol 64:41–47. https://doi.org/10.1016/j.etap.2018.09.009

Tilg H, Cani PD, Mayer EA (2016) Gut microbiome and liver diseases. Gut 65(12):2035–2044. https://doi.org/10.1136/gutjnl-2016-312729

Tang WW, Kitai T, Hazen SL (2017) Gut microbiota in cardiovascular health and disease. Circ Res 120(7):1183–1196. https://doi.org/10.1161/CIRCRESAHA.117.309715

Vitetta L, Bambling M, Alford H (2014) The gastrointestinal tract microbiome, probiotics, and mood. Inflammopharmacology 22(6):333–339. https://doi.org/10.1007/s10787-014-0216-x

Vangay P, Johnson AJ, Ward TL, al-Ghalith GA, Shields-Cutler RR, Hillmann BM, Lucas SK, Beura LK, Thompson EA, Till LM, Batres R, Paw B, Pergament SL, Saenyakul P, Xiong M, Kim AD, Kim G, Masopust D, Martens EC, Angkurawaranon C, McGready R, Kashyap PC, Culhane-Pera KA, Knights D (2018) US immigration westernizes the human gut microbiome. Cell 175(4):962–972. https://doi.org/10.1016/j.cell.2018.10.029

Vlasova AN, Chattha KS, Kandasamy S, Liu Z, Esseili M, Shao L, RajashekaraG SLJ (2013) Lactobacilli and bifidobacteria promote immune homeostasis by modulating innate immune responses to human rotavirus in neonatal gnotobiotic pigs. PLoS One 8(10):e76962. https://doi.org/10.1371/journal.pone.0076962

Wang HW, Liu J, Zhao WP, Zhang ZH, Li SQ, Li SH, Zhu SQ, Zhou BH (2019) Effect of fluoride on small intestine morphology and serum cytokine contents in rats. Biol Trace Elem Res 189(2):511–518. https://doi.org/10.1007/s12011-018-1503-y

Wang HW, Zhao WP, Liu J, Tan PP, Zhang C, Zhou BH (2017) Fluoride-induced oxidative stress and apoptosis are involved in the reducing of oocytes development potential in mice. Chemosphere 186:911–918. https://doi.org/10.1016/j.chemosphere.2017.08.068

Yang B, Wang Y, Qian PY (2016) Sensitivity and correlation of hypervariable regions in 16S rRNA genes in phylogenetic analysis. Bioinformatics 17(1):135. https://doi.org/10.1186/s12859-016-0992-y

Zhou BH, Zhao J, Liu J, Zhang JL, Li J, Wang HW (2015) Fluoride-induced oxidative stress is involved in the morphological damage and dysfunction of liver in female mice. Chemosphere 139:504–511. https://doi.org/10.1016/j.chemosphere.2015.08.030