Fluoride and the Skin Microbiome Hair Follicle Disaster
Fluoride is Genotoxic and the Damage is HERITABLE.
Hello friends. In part two of this series, I began to explain fluorides neutralizing and transformative effects on Interleukin17a [6] and several pathways by which this gene disruption manifests as disease. To go further we will explore how this applies to germinal phenotype expression on fetal follicle induced by fluoride and how this damage is made heritable. We will also make the first connection to how Precision Fermentation can offer the platform to deliver a probiotic solution to the damage fluoride has caused.
As you will see using commensal bacteria to ameliorate these pathologies is not only highly efficacious but the most direct physical method to deliver therapy because it goes to the heart of the damaged metabolism caused by fluoride. The reasons will become evident because of the number of shared obligate biological pathways.
“Here, we first established a male ICR mouse model by treating mice with sodium fluoride (NaF) (100 mg/L) via the drinking water for 91 days. The results showed that fluoride increased the expression of the proinflammatory factors IL-1β and IL-17A, which led to splenic inflammation and morphological injury. The results revealed that fluoride disrupted riboflavin transport, transformation, metabolism, and mitochondrial function. Interestingly, IL-17A partly mediated fluoride-induced riboflavin metabolism disorder and immunotoxicity in the spleen. This work not only reveals a novel toxic mechanism for fluoride but also provides new clues for exploring the physiological function of riboflavin and for diagnosing and treating the toxic effects of fluoride in the environment.” [1]
With these findings we have new evidence that the same disfunctions affecting the body can also affect the microbiome and that these commensal pathways are being modified interdependently. This link is the first step in applying a truly synergistic detoxification regime to removing fluoride in a well designed durable and heritable product.
We can make another commensal link via these transformational modifications in the spleen. The specific transformations caused by fluoride are again shared by our tissues and the microbiome.
“The germinal center (GC) is a dynamic structure formed by proliferating B cells in the follicles of secondary lymphoid organs during T cell-dependent antibody responses to exogenous antigens. GC is composed by a dark zone, enriched in proliferating centroblasts (CBs), and a light zone where CBs migrate and transform into centrocytes (CCs), a minority of which is selected to survive, undergoes Ig class-switch recombination, and differentiates into memory B cells or long-lived plasma cells. CBs express CXCR4 and are attracted to the dark zone by stromal cell-derived CXCL12, whereas CCs express CXCR5 and are recruited to the light zone along a gradient of CXCL13 produced by follicular dendritic cells (FDCs). [3]
This dark zone plays a critical role in preventing the attachment of fluoride ions to the developing follicle. I point you back to article three, in this series, for a more complete explanation as to why melanin repels fluoride from adsorbing to the keratinized surface of said developing follicle.
“Therefore, CXCL12 and CXCL13 play crucial roles in the regulation of GC B cell trafficking. Among the numerous molecules involved in GC formation ... IL-17A belongs to the IL-17 cytokine superfamily, together with 5 additional structurally related cytokines … IL-17A renders freshly isolated tonsil GC B cells competent to migrate to CXCL12 and CXCL13 through a NF-κBp65-dependent mechanism.” [2]
With these relatively new insights into the pathways linking the microbiome to them this information should come as a new idea for most reading this article. But the facts are fluoride is damaging not just your bodies tissues, but your commensal support network that you depend on for survival. Now that we are aware of the mitochondrial link lets now make another strong connection to the potential of novel probiotics to ameliorate the damage caused by fluoride over exposure.
“…fluoride induced hepatointestinal injury and enterohepatic circulation disorder by altering the synthesis, transporters, and FXR-FGF15 pathway regulation of total bile acid. Importantly, the ileum was found to be the most sensitive and fluoride changed ileal microbiome particularly by reducing abundance of Bifidobacterium. While vitamin B2 supplementation attenuated fluoride-induced enterohepatic circulation dysfunction through IL-17A and ileal microbiome, Bifidobacterium supplementation also reversed fluoride-induced hepatointestinal injury.” [3]
And from another paper we also learn the obligate pathway for heritable il17a deficiency fluoride damage to germ cells “… exposure to excessive F levels caused testicular damage, decreased semen quality, negatively affected testicular morphology, and increased the inflammatory response.” The”…findings prove that IL-17A plays a key role in the exacerbation of testicular injuries in F-exposed mice, and that IL-17A deficiency can alleviate F-induced injury by inhibiting the immune response and apoptosis in the testis. These data suggest that targeting IL-17A may be a useful therapeutic strategy for treating F-mediated toxicity in the testis.[4]
Finally to drive the point all the way home and establish with certainty that commensal probiotics are a novel therapy for the remediation of fluoride toxicity let’s look at this final example of a heritable G.R.A.S. commensal bacteria that can become the beginning of a family of new medicines. From 2024 we read:
Fluoride, a ubiquitous environmental pollutant, poses a significant public health threat. Our previous study revealed a correlation between fluoride-induced testicular pyroptosis and male reproductive dysfunction. However, the underlying mechanism remains unclear. Wild-type and interleukin 17A knockout mice were exposed to sodium fluoride (100 mg/L) in deionized drinking water for 18 weeks. Bifidobacterium intervention (1 × 109 CFU/mL, 0.2 mL/day, administered via gavage) commenced in the 10th week. Sperm quality, testicular morphology, key pyroptosis markers, spermatogenesis key genes, IL-17A signaling pathway, and pyroptosis pathway related genes were determined. The results showed that fluoride reduced sperm quality, damaged testicular morphology, affected spermatogenesis, elevated IL-17A levels, and induced testicular pyroptosis. Bifidobacterium intervention alleviated adverse reproductive outcomes. Fluoride-activated testicular pyroptosis through both typical and atypical pathways, with IL-17A involvement. Bifidobacterium supplementation attenuated pyroptosis by downregulating IL-17A, inhibiting NLRP3 and PYRIN-mediated caspase-1 and caspase-11 dependent pathways in testis, thereby alleviating fluoride-induced male reproductive damage. [5]
Thank you for taking the time to read this article series and be open to thinking about probiotics as a novel chassis for the delivery of targeted therapy and medicine. If you see that these chassis can not only fix the damage done to an individual but offer corrective modifications, that are G.R.A.S., to be inherited by your potential offspring is groundbreaking. This conversation needs to be had.
[1] Fluoride induces immunotoxicity by regulating riboflavin transport and metabolism partly through IL-17A in the spleen
https://pubmed.ncbi.nlm.nih.gov/38968825/
[2] IL-17 superfamily cytokines modulate normal germinal center B cell migration
https://pubmed.ncbi.nlm.nih.gov/27566830/
[3] Fluoride induces hepatointestinal damage and vitamin B2 mitigation by regulating IL-17A and Bifidobacterium in ileum
https://pubmed.ncbi.nlm.nih.gov/39097090/
[4] Interleukin 17A deficiency alleviates fluoride-induced testicular injury by inhibiting the immune response and apoptosis
https://pubmed.ncbi.nlm.nih.gov/33297146/
[5] Fluoride induces pyroptosis via IL-17A-mediated caspase-1/11-dependent pathways and Bifidobacterium intervention in testis
https://pubmed.ncbi.nlm.nih.gov/38554964/
[6] Interleukin-17A
https://en.wikipedia.org/wiki/Interleukin-17A