72 healthy female mice were exposed to fluoride at concentrations of 0, 25, 50 and 100 mg/Liter. While this is far higher than the 1 mg/Liter typically found in municipally treated water, scientists typically use water fluoride levels at a 10-fold higher concentration with mice to achieve the same blood fluoride levels found in humans. After 70 days of drinking fluoridated water, mice showed damage to their microbiome in 3 main areas. 1) Reduced amounts of short chain fatty acids (which prevent autoimmunity & reduce inflammation) - 2) Reduced antimicrobial peptides (which eliminate viruses, harmful bacteria and fungi) - and 3) Reduced number of goblet cells (which produce mucin needed for maintaining the intestinal barrier and preventing leaky-gut.
As the full study are behind a "pay-wall," I am not able to get detailed results of specific fluoride levels and biological effects. However, considering that fluoride can have any effect on this critical defenses. for these changes.
ABSTRACT
Colon microenvironment and microbiota dysbiosis are closely related to various human metabolic diseases. In this study, a total of 72 healthy female mice were exposed to fluoride (F) (0, 25, 50 and 100 mg/L F−) in drinking water for 70 days. The effect of F on intestinal barrier and the diversity and composition in colon microbiota have been evaluated. Meanwhile, the relationship among F-induced colon microbiota alterations and antimicrobial peptides (AMPs) expression and short-chain fatty acids (SCFAs) level also been assessed. The results suggested that F decreased the goblet cells number and glycoprotein expression in colon. And further high-throughput 16S rRNA gene sequencing result demonstrated that F exposure induced the diversity and community composition of colonic microbiota significantly changes. Linear Discriminant Analysis Effect Size (LEfSe) analysis identified 11 predominantly characteristic taxa which may be the biomarker in response to F exposure. F-induced intestinal microbiota perturbations lead to the significantly decreased SCFAs levels in colon. Immunofluorescence results showed that F increased the protein expression of interleukin-17A (IL-17A) and IL-22 (P < 0.01) and disturbed the expression of interleukin-17 receptor A (IL-17RA) and IL-22R (P < 0.05 or P < 0.01). In addition, the increased expression of IL-17A and IL-22 cooperatively enhanced the mRNA expression of AMPs which response to F-induced microbiota perturbations. Collectively, destroyed microenvironment and disturbed AMPs are the primary reason of microbiota dysbiosis in colon after F exposure. Colonic homoeostasis imbalance would be helpful for finding the source of F-induced chronic systemic diseases.
Snippets from the orginal article
Animals and treatment
A total of 72 healthy female 21-day-old Kunming mice were purchased from the Experimental Animal Centre of Zhengzhou University, which were fed with a standard diet and housed under a 12 h light/dark cycle at a temperature of 22 °C ± 2 °C room for one week. After 7 days of acclimation, the mice were randomly divided into 4 groups of 18. The experimental design is as follows: mice in control group were given distilled water and standard diet, whereas the mice in the F groups were fed with...
Effect of F on the morphology, goblet cells number and glycoprotein expression in colon
Fig. 1 showed that, compared with the control group (Fig. 1A1), F exposure induce histopathological lesions in colonic tissues consisting of shortening and atrophy of colonic gland, mild to moderate necrosis of enterocytes, and a decrease in the number of goblet cells (Fig. 1B1, C1 and D1). With increasing F dose intake, the damage of colon tissue was more serious.
AB-PAS and PAS staining showed the distribution of goblet cells and glycoproteins. Obviously, the numbers of AB-PAS positive cells
Discussion
The intestinal barrier plays a pivotal role in maintaining the intestinal homoeostasis. Mucin glycoproteins secreted by goblet cells assemble into mucus layer is the front line of host defense against endogenous and exogenous irritants which play an important role in intestinal infections (Kim and Ho, 2010). Mucin glycoproteins secreted by goblet cells assemble into mucus layer is the front line of host defense against endogenous and exogenous irritants which play an important role in
Conclusion
Our results revealed that F destroy colonic microenvironment, lead to decrease the goblet cells number and glycoprotein secretion. Meanwhile, F disturbed AMPs expression by increased the level of IL-17A and IL-22. Destroyed microenvironment and disturbed AMPs are the primary reason of microbiota dysbiosis in colon after F exposure (Fig. 7). These results would be helpful for understanding the mechanism of F-induced colonic homeostasis imbalance. Colonic homoeostasis imbalance may be the source