Quite Possible that Il-17 Inhibition Can Rejuvenate Stem Cells

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Also indole byproducts from tryptophan could be THEE REASON for L. Reuteri rejuvenation effect in another study.

Interleukin-17 (IL-17) can play a role in stem cell renewal, particularly by promoting the proliferation and differentiation of certain stem cell populations, contributing to tissue repair and regeneration in various contexts, although its exact function depends on the tissue type and inflammatory environment involved; in some cases, high levels of IL-17 can also negatively impact stem cell function by disrupting their niche or promoting excessive differentiation.



Key points about IL-17 and stem cell renewal:
  • Tissue repair and regeneration:
    Studies show that IL-17 can stimulate the proliferation of stem cells in tissues undergoing repair following injury, like in the gut epithelium where it helps replenish damaged cells by promoting epithelial stem cell division.

  • Mesenchymal stem cells:
    IL-17 has been found to promote the proliferation and differentiation of mesenchymal stem cells (MSCs), which can contribute to bone regeneration by stimulating osteoblast activity.


  • Muscle regeneration:
    Research indicates that IL-17 produced by certain immune cells can contribute to muscle regeneration by promoting the proliferation of muscle progenitor cells.


  • Potential downsides:
    While beneficial in certain situations, excessive IL-17 production can lead to inflammation and disrupt the stem cell niche, potentially impairing stem cell function.


  • Signal transduction:
    IL-17 exerts its effects on stem cells through specific receptors, activating signaling pathways that lead to changes in gene expression, promoting cell proliferation and differentiation.


  • ______

    Supplement with tryptophan-associated metabolites improved engraftment efficiency of aged HSCs​


    Many microbiota-derived metabolites play vital roles in the regulation of host inflammation and hematopoiesis via the bloodstream.21 To identify the microbiota-derived metabolites responsible for restoration of aging hematopoiesis, LC-MS untargeted metabolomic analysis of fecal samples was performed in mice upon FMT.

  • Principal component analysis indicated that fecal samples of FMT-YA displayed distinct metabolite profiles compared with the FMT-AA group (Figure 7A-B). Specifically, tryptophan-associated metabolites, including tryptophan, indole-1-acetic acid (IAA), and indole and indole-3-carbinol (I3C), were significantly upregulated in FMT-YA mice (Figure 7C). Upregulation of tryptophan-associated metabolites in FMT-YA mice was also observed in PB and BM plasma (supplemental Figure 6A-B).

  • Of note, indole and indole derivatives could prevent oxidative stress and reduce inflammatory response in vitro and in vivo.35,36

  • We then determined the enriched pathways of these metabolites by Kyoto Encyclopedia of Genes and Genomes analysis. Pathways related to various amino acids were enriched in FMT-YA mice, especially in phenylalanine, tyrosine, and tryptophan-related metabolites (Figure 7D). Spearman correlation analysis was performed to explore the potential association between the gut microbiota and metabolites.

  • Lachnospiraceae are positively correlated with tryptophan, indole, and indole derivatives (supplemental Figure 6C-D), which was consistent with previous reports that Lachnospiraceae were involved in the production of tryptophan and indole.37







  • Notice in this chart that when tryptophan metabolites(indole) go down then IL-17 goes up and stem cell renewal goes down:












  • Lactobacillus reuteri (L. reuteri) is a probiotic bacteria known to produce indole derivatives, particularly indole-3-aldehyde (I3A), which are metabolites derived from tryptophan and play a significant role in modulating immune response and gut health by activating the aryl hydrocarbon receptor (AhR) pathway; essentially, L. reuteri helps regulate the immune system through the production of these indole compounds.



    Key points about L. reuteri and indole:
    • Indole production:
      L. reuteri is one of the primary bacteria in the gut microbiome that can metabolize tryptophan into various indole derivatives, including I3A.

    • Aryl hydrocarbon receptor (AhR) activation:
      Indoles produced by L. reuteri act as ligands for AhR, a transcription factor that influences immune cell function and can regulate inflammation.


    • Immune modulation:
      By activating AhR, L. reuteri-derived indoles can influence the development and function of immune cells, potentially contributing to anti-inflammatory effects.


    • Potential therapeutic applications:
      Research suggests that L. reuteri and its indole metabolites may be beneficial in conditions like atopic dermatitis, cancer, and inflammatory bowel disease due to their immunomodulatory properties.

      +++++++++++++++

      Takeaway: obvious supplementation with indole compounds like I3A
    • Available here:
    • https://plantcelltechnology.com/pro...6FvdPDeSAwJLnN8RpyMnA0knBkAfTN7lfbdTaIyHYJPar

  • Problem is though and others have found out that DIM just doesn't work for Androgenetic Alopecia perhaps due to it's very low bioavailability and other factors.

  • https://link.springer.com/article/10.1007/s00044-024-03277-1
  • Despite their beneficial biological activities, indoles have clinical limitations due to poor bioavailability, solubility, rapid metabolism, and limited membrane permeability.
___________

3-indoleacetic acid (3-IAA) – Exploring its impact on human health and metabolism​

biocrates.com

3-indoleacetic acid (3-IAA) – Exploring its impact on human health and metabolism - biocrates life sciences ag

The metabolite of this month is 3-IAA, known as the most common plant growth hormone.
biocrates.com biocrates.com
 
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Thus, the improvement of intestinal barrier integrity may be a vital link in rejuvenating aged HSCs with young microbiota. Furthermore, we observed a lower expression of intestinal inflammatory markers in FMT-YA(me: YA = young) mice, including interferon gamma, IL-6, and IL-4 (Figure 5F-H). Taken together, these data suggest that young gut microbiota was supportive and protective for intestinal barrier integrity in aged mice.
 
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Pursuing intestinal barrier integrity and what to do about it as Jeffrey Mark MD explains:
www.therealgutdoctor.com

The Surprising Link Between Leaky Gut and Hair Loss - Functional Medicine Doctor | The Real Gut Doctor In San Ramon

Exploring the link between leaky gut and hair loss. Discover how gut health can impact hair growth and strategies to address the issue.
www.therealgutdoctor.com www.therealgutdoctor.com

"When I started to notice my hair thinning, I never imagined that the root cause might be inflammation stemming from my gut. It turns out that an unhealthy gut can lead to a condition known as 'leaky gut', where the intestinal barrier becomes compromised. This allows toxins and inflammatory substances to leak into the bloodstream, which can trigger inflammation throughout the body, including the scalp.Chronic inflammation can disrupt the normal hair growth cycle, leading to hair loss or thinning. It's a complex process, but essentially, when the body is in a state of inflammation, it can signal hair follicles to enter the resting phase prematurely, halting hair production.Moreover, inflammation can damage the hair follicles directly, preventing new hair from growing.To better understand the impact, here's a list of factors that can exacerbate inflammation"
 
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Akkermansia muciniphila (Akk), a mucin-degrading bacterium found in the mucus layer of the human gut, is a potential probiotic as it helps regulate the immune system and reduce inflammation.1, 2 However, despite growing interest in Akk, its precise mechanisms of action and potential human health applications are yet to be fully elucidated.

Several studies have examined the potential benefits of Akk as an oral supplement, particularly in the form of capsules and beverages. For example, live Akk bacteria significantly reduced insulin resistance, total cholesterol, low-density lipoprotein cholesterol, and body weight compared to the placebo group.3,

4 Akk improves gut barrier function and reduces autoimmune and chronic inflammatory diseases.5 In addition, daily administration of Akk prevents age-related decline in colonic mucous layer thickness, thereby attenuating inflammation and immune-related processes in old age, suggesting that Akk may contribute to the promotion of healthy aging.6 These results suggest that Akk may have potential health benefits. However, further research is required to fully understand its effects on human health and determine how best it can be incorporated into diets.


It is the equivalent of finasteride at least in the mice on countering the testosterone injections. Is is without finasteride side effects would be the question that needs answered.

The hair growth efficacy of Akk was comparable to that of finasteride, which was used as the positive control drug. No significant change in body weight was observed in any of the experimental groups (Figure 1C).

AKT plays a critical role in hair growth regulation by promoting the survival and proliferation of hair follicle cells.15

Live and pasteurized Akk increased the testosterone-induced inhibition of p-AKT and exerted a more pronounced increase in AKT phosphorylation than finasteride (Figure 3A,B)

. Live and pasteurized Akk increased β-catenin levels, a key regulatory protein in hair growth,16 although significant differences were not observed between the live and pasteurized Akk groups. Akk also increased the expression levels of cyclin D1, which is crucial in regulating cell cycle progression.17 Furthermore, we observed a significant increase in the family members of the fibroblast growth factor, including Fgf7, Igf1, Fgf7, Fgf10, and Fgf21 in the Akk-treated groups (Figure 3C). Collectively, Akk appears to influence hair growth by regulating cell proliferation through β-catenin activation, cell cycle progression, and growth factor expressions.
 
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