Gram negative bacteria, endotoxin, jab adjuvants, and prenatal risks.

Lack of vitamin K2 and disrupted retinoid metabolism might be factors in prenatal loss of defects post CoV jabs.

Geoffrey Pain, PhD, gave a talk/Spaces on X.com yesterday which you can listen to as a recording here, x.com. It was hosted by Aussie Nomad, @damonmcclure3. Geoffrey Pain, PhD, is a chemistry focused scientist, an educator of college students. He is highlighting major errors or suspicions about the “high school student science fair team” who found a significantly large amount of DNA plasmid contamination in vials of Pfizer CoV injections….. but not much in the Moderna sample is part of his concern, BUT Anandamide’s post said that there were only Pfizer vials in the images. See the Substack,Anandamide (Kevin McKernan), who breaks it down clearly here, open.substack.com/pub/anandamide/p/sanity-sunday-and-psyop-soup.

Sanity Sunday and PsyOp Soup

The point of DNA plasmid contaminants being found in the Pfizer vials, the risk we are facing, is potentially getting cancer from there having been uptake of SV40 containing DNA plasmids. Or chimeric spike genetics may become part of a cell and long-term spike production would worsen their health and could spread in exosomes they release in breath or sweat.

• See this video for an industry person discussing gene uptake as a observed event. (x.com/DIY_Tardis) *Note that the comment with the video is satire, he is not really encouraging getting booster jabs.

• Same here: click for the video, second image, quoted below: (https://x.com/DIY_Tardis/status/1879023742170579122).

"We must stop messenger RNA (injections) at all costs."

"It is not only mad, it is evil."

~ Like exposing children to radium (radioactive poisoning) just to see what happens to them within 10-20 years.

- Angus Dalgleish, an expert in the early research on using mRNA for cancer 'vaccines' but the technique was so dangerous that approval could not be received to trial it for cancer patients. Click for video: (x.com/DIY_Tardis).

“Angus Dalgleish is a professor of oncology at St. George’s, University of London, best known for his contributions to HIV/AIDS research.” Wikipedia, Click for video interview of Angus Dalgleish discussing mRNA history of research as a ‘vaccine’ against cancer - so dangerous it turned out, that it was never approved for clinical trials on cancer patients. Video: (x.com/DIY_Tardis).

• A comprehensive list of reported adverse effects, with additional explanatory information about some of the conditions listed. (journal.rajeshtaylor.com/list-of-adverse-events-in-pfizers-covid-19-mrna-vaccine-post-marketing-experience-report/)

• Geoffrey Pain, PhD’s series of posts on the topic are linked within this post. He also discussed a problem in the CoV injections that also may add to risks seen from other traditional vaccines too - bacterial endotoxin used as an adjuvant.

The rest of this post is about LPS endotoxin and dietary strategies for reducing the inflammatory risks. LPS endotoxin is produced by Gram-negative bacteria like E. coli and they can be colony forming - make a biofilm cluster/capsule that makes them resistant to antibiotics and sterilizing cleansers. LPS endotoxin is used as an adjuvant in many vaccines - and it might add to negative reactions. However, Anandamide said no live E. coli contaminants have been found in CoV injections tested by various independent researchers. open.substack.com/pub/anandamide/p/sanity-sunday-and-psyop-soup.

Chimeric spike is known to increase negative effects of LPS though and addressing it therapeutically has been part of my CoV protocol since 2021, this post has some formatting issues as it was copied from transcendingsquare.com, and is so long it broke Substack and I can’t edit it, :-).

Nicotine aside

»>Aside: Nicotine is worth watching the news regarding: Leading Report, @LeadingReport, “BREAKING: Biden’s rule to effectively ban cigarettes by slashing nicotine by 98%, likely to be published by the FDA very soon.” (x.com/LeadingReport)

Ten milligrams, about 10 cigarettes worth, might be protective (against the cholinergic blocking effects of the S1 subunit of the chimeric spike), spread out over the 24hrs somewhat, tiny bits more often to maintain mood and body protection. It can be easy to overuse the lozenges and is addictive. Caution is warranted but the nicotine itself is not cancer causing like the smoke or additives of cigarettes are. And… does Biden really think no one will roll their own tobacco cigarettes? The smoke toxins wouldn’t be worth a 2% nicotine cigarette, and what kind of filler ‘tobacco’ would be used to reduce the nicotine content that much?

11) LPS toxicity enhanced by Spike protein,

- and increases inflammation.

Spike protein enhances bacterial LPS toxicity, "This study shows that it binds and aggregates bacterial lipopolysaccharide, exacerbating (innate, TLR4) inflammatory signaling." @gerdosi, (27):

Background info:

“Lipopolysaccharides (LPS) are the major elements of the cell walls of gram-negative bacteria; they are endotoxins, which cause a strong response in normal animal immune systems and have been used in inducing immune stress in animal models [1].

• LPS activates monocytes/macrophages to secrete various inflammatory cytokines [2],

• stimulates microglia, and decreases glutamatergic transmission that leads to memory deficits [3].

• LPS also damages the intestinal barrier function [4], restricts the expression of innate immune receptors in intestinal epithelial cells [5],

• and enhances neutrophilic lung inflammation and pulmonary edema [6].

Antibiotics have been reported to counteract a variety of problems caused by LPS [7,8,9]. Most synthesized antibiotics, however, are potentially unsafe because they may increase drug resistance in human pathogens [10]. To avoid this negative influence, much legislation has been adopted in Europe and most countries worldwide to ban or restrict the use of chemically synthesized antibiotics in animal feed (such as growth promoters), which has triggered a need to find effective, safe and natural alternatives to antibiotics [11,12,13].” (23) *Bullet points added for emphasis.

• Copper loaded chitosan is also discussed as a possible therapeutic rather than using antibiotics (a standard used for bacterial endotoxin LPS problems which is now limited for use in chickens; agriculture industry article). (23)

• Immunomodulators that promote Nrf2 help reduce risk from LPS.

• Nrf2 Promoting Foods/nutrients, [see above graphic *this is from a different post]. (5, 6)

• Quercetin has been found helpful against LPS toxicity in an animal-based study. (85)

Mushrooms are protective:

"Mushroom polysaccharides are seen as a biological regulator with various physiological activities obtained from the mycelium of ascomycetes and basidiomycetes Subphylum mushroom (Agaricus bisporus, agaric, Ganoderma lucidum, etc.) through deep liquid fermentation. They play an important role in regulating animal immune function through stimulating natural killer cells involving neutrophils and macrophage dependent immune system responses, in addition to modifying receptors such as those of dectin-1, toll-like receptor-2, scavengers and lactosylceramides [14]. Studies on poultry have shown that mushroom polysaccharides can enhance the specific immunoglobulin level of Eimeria tenella infected chickens [15], stimulate the growth of immune organs such as the spleen, thymus and bursa [16], and positively modify the intestinal microbiota in infected chickens [17]." *Eimeria tenella also makes lipopolysaccharide. (23)

From my pomegranate paper Tables - bitter taste receptors are protective because they work with or modulate TRP channels:

Bitter taste receptors work with TRP ion channels and voltage gated calcium channels within the kidney. (Zhou and Greka, 2016) TRPC5 is highly expressed in the kidney on podocytes and is involved in calcium ion influx. Inhibition or genetic deletion of TRPC5 channels reduced filtration barrier injury when lipopolysaccharide (LPS)- or protamine sulfate (PS) was given to induce kidney injury in mouse models. The mice were protected from albuminuria when TRPC5 channels were inhibited or knocked out. (Schaldecker, et al, 2013; Zhou and Greka, 2016)

~~

Immunomodulatory – reduces IL-6, TNF-α, increases nitric oxide and is anti-inflammatory. (Elkady, et al., 2021, Figure 3; Mastrogiovanni, et al., 2019; Sayed, et al, 2022) PPE reduced IL-6 and TNF-α in a dose related manner following LPS treatment in a cell study. The highest dose, 300 micrograms PPE reduced IL-6 after LPS treatment to below baseline and brought TNF-α near to baseline: Average IL-6 (pg/ml) in untreated cells, 106.7, in cells treated with LPS, 640.3, in cells treated with LPS and extract, 63.3; Average TNF-α (pg/ml) in untreated cells, 64.3, in cells treated with LPS, 987.3, and in cells treated with LPS and extract, 77.7. See Figure 1 for data for 75 and 150 µg extract. (Qabaha, et al., 2019, Figure 1)

~~

Anthocyanidins (blue/red pigments in berries, pomegranate, black beans, etc) are also protective against LPS effects. (Hou, et al, 2005)

~~~

The following is about Toll Like receptor 4 and LPS endotoxin and microbiome - we need the good guy species to help keep the bad ones in check. This overlaps with the ototoxicity series somewhat, but I need to spend more time organizing the microbiome material. Presenting as is:

Bacterial Endotoxin, a different known issue in the CoV injections, most any brand, and may be an adjuvant used in other traditional types of vaccines.

Bacterial endotoxin is very inflammatory and could be causing a variety of health symptoms post CoV injections, in addition to other chimeric spike effects.

Gram negative colony forming bacteria are damaging to health in many ways and produce the LPS endotoxin which triggers inflammatory protein production within the body. It or the bacteria are added on purpose as an ‘adjuvant’ to stimulate a strong immune response.

If you guessed pomegranate peel extract reduces risks from LPS or Gram-negative bacteria, then you get a gold star for your sticker chart. However, if you guessed other sources of catechins/ellagitannins, then you also get a gold star. I mention pomegranate the most because I have spent the most time looking into its benefits and the benefits are so numerous, and consistently beneficial, that there are loads of research studies using it now. But there are still only a few human clinical trials because of the expense of human trials, but the cell or animal studies show a pattern of safety and efficacy. Also synergistic value in extracts of the whole peel, rather than isolates - however the postbiotic urolithins were found to be potent against LPS endotoxin.

Balance within the microbiome is achieved in part by beneficial or benign species helping to control negative species from growing into a dominant species - more of an infection than a balanced community.

Our intestinal lining is protected by a layer of mucus - our own biofilm or glycocalyx. Gram-negative and certain other types of bacteria are harder to kill because of their forming a cluster or colony surrounded by a mucus biofilm too.

“The integrity of the gut mucosal barrier is essential for maintaining a chemical and physical barrier against food, environmental antigens, and microbes (28, 29). Goblet cells migrate up the villi after differentiating from crypt stem cells and turn over with the epithelial layer every 3–5 d. Goblet cells secrete mucins, particularly mucin 2 (Muc-2), that contribute substantially to the maintenance of mucosal integrity (30). Mucin secretion is regulated by a complex network of cholinergic stimulation and T-helper 2 (Th2) cytokines IL-4 and IL-13 (31–35).” (Blumberg, et al., 2016)

Without cholinergic stimulation, IL-4 and IL-13 cytokines, the biofilm mucus layer won’t form to protect the gut lining. Colitis is a symptom of cholinergic blocking snake venom or Cona snail toxins.

“Mammalian Toll-like receptors (TLRs)⁴ constitute a distinct and phylogenetically ancient class of the IL-1/TLR supergene family. TLRs recognize molecular patterns derived from pathogens, such as bacteria and fungi, and their activation results in the production of proinflammatory antimicrobial mediators (1). TLR4 was the first mammalian TLR identified (2) and its activation by LPS, a component of the outer cell wall of Gram-negative bacteria, is well established based on genetic studies (3). Effective TLR4 activation by LPS requires the interaction of LPS with CD14, which is enhanced by LPS-binding protein (3), and MD-2, a protein that associates with surface TLR4 molecules (4, 5). TLR4 activation increases expression of proinflammatory cytokines, such as TNF-α and IL-12, and costimulatory molecules, such as CD80 (B7-1) and CD86 (B7-2) (2, 6, 7) via a MyD88/IL-IR-associated kinase/TNFR-associated factor 6/NF-κB signaling pathway (8, 9) as well as by a poorly characterized MyD88-independent pathway (6).” (Dabbagh, et al., 2002)

Cranberries/extract helped the gut microbiome in a study mentioned in this review and a fiber diet rich diet also helps promote the butyrate producing species the colon needs for health. Modern standard diets tend to promote gut dysbiosis. Alcohol excess is also a gut microbiome negative. (Hills, et al., 2019) Zinc deficiency might add to risk of Gram-Negative bacteria because a zinc finger transcription protein is needed for us to be able to make bitter taste receptors and bitter taste receptors play a role in gut health. (Sekine, et al, 2012) Zinc is needed in significant amounts in our diet to feed the butyrate producing species. (Tako, Koren, 2020) Negative species can survive without zinc adequacy.

Avoid alcohol excess: “In alcoholic liver disease, alcohol consumption causes gut permeability by reducing the expression of REG3, a bactericidal protein normally responsible for restricting the mucosal colonization of luminal bacteria [57].” […]

“Autism spectrum disorder, which is often associated with constipation, has been connected to gut dysbiosis in the form of an increased Firmicutes/Bacteroidetes ratio and high levels of facultative anaerobes Escherichia/Shigella and the fungal genus Candida [60,61]. It is suggested that leaky gut contributes to the pathogenesis of autism by increasing systemic metabolites that alter the neuroimmune and neuroendocrine systems, thus affecting the brain and neurodevelopment [61,62,63].” […]

“Dysfunctions in GABA receptor signaling are implicated in anxiety and depression, and beneficial bacteria Lactobacillus and Bifidobacterium convert the amino acid glutamate into GABA [78,79].” […]

Eat inulin fiber: “In a study comparing young and middle-aged mice, dietary supplementation with prebiotic inulin was observed to increase Bifidobacterium and Akkermansia, reduce neuroinflammation and anxiety, and improve cognition in middle-aged mice [81]. The fact that alterations in gut microbiota can provide cognitive symptom relief could offer one basis for the relationship observed between quality of diet and one’s mental health status [82].” […]

“Both obesity and diabetes are characterized by insulin resistance and low-grade inflammation. A mouse study by Cani et al. points to bacterial LPS as a causative factor of insulin resistance, obesity, and diabetes [106]. Feeding and fasting cycles increased or decreased plasma levels of LPS, respectively, and metabolic endotoxemia was observed in mice fed a four-week high-fat diet that increased the proportion of gram-negative bacteria in the gut, raising plasma LPS concentration by a factor of two to three. Endotoxemia could also be induced via subcutaneous infusion of LPS for four weeks, resulting in weight gain and increased fasting hyperglycemia and hyperinsulinemia. LPS produces inflammation in adipocytes through the activation of toll-like receptor 4 signaling [107]. Thus, prebiotics that improve intestinal microbiota and reduce intestinal permeability are of potential clinical use for the treatment of diabetes [108,109]. Randomized controlled trials have reported improvements in glycemia and cardiovascular markers in T2D patients taking resistant starch, resistant dextrin, or inulin [110].”

This kind of fiber, not wheat bran: “Soluble, nonviscous fiber (inulin, wheat dextrin, resistant starch) is readily fermented.” […]

“In a 12-week mouse study, supplementing a high-fat diet with 10% fermentable flaxseed fiber dramatically increased butyrate production, energy expenditure, and Bifidobacterium and Akkermansia levels, while countering weight gain [118]. In contrast to the Western diet, consuming daily servings of fiber, fruit, and vegetables promotes the alpha diversity of bacterial species in the gut [12,102,119,120,121].” (Hills, et al., 2019)

PDL-1 - cancer promoter is inhibited by pomegranate peel urolithin A. (Shen, et al., 2023)

Urolithin A is not IN the pomegranate peel itself. We need butyrate producing species to make that from ellagitannins. Catechins, hydrolysable tannins, EGCG, are other names to look for if interested. Foods/beverages include green and black tea, Macha, goji berries, other berries, sumac powder or tea (edible magenta red berries, not the poisonous white ones), persimmons, quince, other things probably. Mother Nature’s cabinet overflows us if we choose to look. My promoting pomegranate is really promoting catechins - eat Sumac powder in Zaatar spice blend. Eat persimmons. Drink green tea. Nature offers us oodles of choices, but the medical focused doctors have blinders on to phytonutrients on average, not seeing them as a viable solution or even seeing them at all. You can’t read what you aren’t looking at, or aren’t shown, or are shown in a negative way, so you really don’t ever want to look at it.

The fact that mainstream media came out strongly against pomegranate years prior to CoV era (ridiculed in POM Wonderful commercials - the purple POM monster mascot, and on Youtube, and in other ways), and are still at it, suggests that we are not supposed to look at pomegranate for health, (or citrus peel, or garlic, or vitamin C, etc.) Maybe the POM Wonderful purple monster was supposed to suggest to shoppers that pomegranate juice helps calm anxiety and stress, which it can. But they were odd commercials. Aside: Boycott POM and the Wonderful company as the owners, the Resnicks, own much of California’s water supply, over 50%… and that just isn’t right. (forbes.com, 2021)

Persimmon and persimmon leaves or pomegranate leaves are sources of the ellagitannins. The medical insurance industry likes to have BIG bills, not practically free bills, as the (Un)Affordable Care Act set a cap on profit for insurance companies at 15% of the medical bill. That was supposedly to make health care more affordable but it led to the insurance companies encouraging padded bills. Fifteen percent of a million-dollar bill is $150,000, while it is only $1.50 if the bill was $10. If your copay is 20%, then that might seem like you are saving money on the $150,000 bill, you only owe $30,000. A ten dollar bill is easier to find in most people’s wallets, than $30,000.

AND the pomegranate peel would likely be more effective and safer for overall health - fewer side effect risks than most standard medications.

Pomegranate peel helps kill off negative microbiome species while also supporting growth of beneficial species. It is naturally a “smart” antibiotic… and antifungal, antiworm, antiparasitic. The beneficial effects of pomegranate peel are simply extremely numerous, and dose does matter, too much would be an irritant and similarly to aspirin/NSAIDs, it could cause COX2 inhibition symptoms if used in excess.

Urolithins, a postibiotic made from ellagitannins reduces Gram Negative Bacterial colony growth.

Short story on what to do about endotoxin risk - promote healthier butyrate producing species and urolithin production by eating a diet with adequate zinc, resistant starches and ellagitannin foods or beverages. The ellagitannins can be made into urolithins by butyrate and other beneficial species. The urolithin A and B showed significant reduction in Gram negative bacterial colony formation. (Shen, et al., 2023) *I get the impression that injections may have live colony ‘contaminants’ to produce the endotoxin, that is used as an immune response generating adjuvant.

Urolithin A is available as an isolate/supplement, but it would be expensive and would not be improving the gut microbiome balance of butyrate producing species which are critically important for colon health, preventing SIBO, and are specifically knocked out by chimeric spike effects. Butyrate species also may be making vitamin K2 for us which has anti-calcification effects for our soft tissues, pineal gland, and bone spur formation. A sudden lack in vitamin K/K2 could add to excessive menstrual bleeding symptoms. Generally, vitamin K2 is sufficient if the gut microbiome is healthy, as beneficial species make vitamin K2 for their own needs, and that gives us plenty too.

Newborns are routinely given vitamin K injections, and many may not need it, but others could. A study found that mothers who used steroid treatment prenatally were more likely to have newborns deficient in vitamin K and needed the supplemental injection. (Liu, et al., 2023) That observation is likely due to steroid treatment having a negative effect on the gut microbiome diversity. Any type of ongoing stress is similar in that we are producing our own ‘steroids’ and gut dysbiosis is seen with chronic stress. Colitis or irritable bowel syndrome are common with chronic stress.

An animal-based study on gut microbiome effects of prednisone treatment, found that Triangularia and Ciliophora species were reduced and fungal species changed in a negative direction. (Li, et al., 2023) Triangularia bacterial species produces chemicals that help protect against fungus and against Gram positive bacterial species. (Harms, et al., 2021) Ciliophora are protozoa - larger than bacteria and they eat bacteria and fungi. They generally are a commensal, benign species of the gut of invertebrates and mammals. They are known for causing fish illness in farmed fish and may make insects sick. ‘Ciliophora - an overview’ | ScienceDirect Topics.

“Our data showed that there were no changes in the richness of gut mycobiome in rats after prednisone treatment, but the diversity increased significantly. The relative abundance of genera Triangularia and Ciliophora decreased significantly. At the species level, the relative abundance of Aspergillus glabripes increased significantly, while Triangularia mangenotii and Ciliophora sp. decreased. In addition, prednisone altered the gut fungi-bacteria interkingdom interactions in rats after prednisone treatment. Additionally, the genus Triangularia was negatively correlated with m-aminobenzoic acid, but positively correlated with hydrocinnamic acid and valeric acid. Ciliophora was negatively correlated with phenylalanine and homovanillic acid, but positively correlated with 2-Phenylpropionate, hydrocinnamic acid, propionic acid, valeric acid, isobutyric acid, and isovaleric acid.”

• ‘Long-term prednisone treatment causes fungal microbiota dysbiosis and alters the ecological interaction between gut mycobiome and bacteriome in rats’ (Li, et al., 2023)

The zinc need is significant, the beneficial species are consuming about 30% of our daily dietary zinc - which means if we aren’t eating much zinc, than those species simply won’t grow well. Unhealthy gut microbiome species can tolerate a low mineral, high junk food diet. (Tako, Koren, 2020)

Bacterial Endotoxin in Vaccines ****This section is Brave AI’s take on the topic, with some quotes I added.

Colony forming bacteria, particularly those from Gram-negative species, can produce endotoxins as part of their outer cell wall. These endotoxins, which are lipopolysaccharides (LPS), can be present in bacterial vaccines and may act as adjuvants, enhancing the immune response. However, the presence of endotoxins can also lead to adverse effects such as fever, shock, and death due to their inflammatory properties.

“2.5. Colony Formation

A total of 1 × 10³ GBM cells were seeded on the 3.5 cm dish and treated with urolithin A or urolithin B for 14 days. Medium containing urolithins was renewed every three days.” (Shen, et al., 2023)

Take home point - more Urolithins, less colony forming bacterial growth. “Urolithin A and urolithin B inhibit GBM cell growth. U251 human (A) and ALTS1C1 mouse (C) GBM cells were administrated with urolithin A for 14 days. Medium containing urolithin A was replaced every 3 days. Cells were incubated with 0.1% crystal violet for 1 h. Colony formation was captured using a microscope. Quantitative results shown in (B,D). (E) U251 human GBM cells were treated with various concentrations of urolithin A (2, 5 and 10 μM) for 24, 48, and 72 h. The cell viability was detected by MTT assay. Each bar represents the mean ± standard error of the mean (n = 3). * p < 0.05 compared with the control group.” (Shen, et al., 2023)

In vaccine production, the amount of endotoxin remaining in the final vaccine formulation is carefully controlled. [*Geoff Pain, PhD, commented that this is not a factual statement by the AI - the vaccine industry can’t really guarantee the amount of endotoxin. See the replies to this post.] Purification steps are used to reduce the level of endotoxins, and residual bacterial protein, including potential endotoxins, is monitored during the manufacturing process. For example, the DPT (diphtheria, pertussis, tetanus) vaccine, which includes toxoids from exotoxin-producing bacteria, is administered with adjuvants to enhance the immune response and boost long-term immunity.

To mitigate the risks associated with endotoxins, vaccine manufacturers often use the Limulus amebocyte lysate (LAL) test to detect and quantify LPS in vaccine formulations. This test is based on the reaction of LPS with factors in the horseshoe crab’s blood, leading to a gel-clot formation that can be quantified. The LAL test can detect endotoxins down to very low concentrations, ensuring that vaccines meet safety standards.

In summary, while colony-forming bacteria can produce endotoxins that act as adjuvants in vaccines, their presence must be carefully managed to avoid adverse reactions. Vaccines are rigorously tested to ensure that the level of endotoxins is minimized and does not pose a risk to recipients.

1. pmc.ncbi.nlm.nih.gov, Bacterial endotoxins and exotoxins in intensive care medicine - PMC

2. fda.gov, Bacterial Endotoxins/Pyrogens | FDA

3. sciencedirect.com, Endotoxin - an overview | ScienceDirect Topics

4. sigmaaldrich.com, Cell Culture FAQs: Bacterial Endotoxin Contamination

5. sciencedirect.com, Bacterial Vaccine - an overview | ScienceDirect Topics

6. en.wikipedia.org, Exotoxin - Wikipedia

7. https://search.brave.com/search?q=colony+forming+bacteria+as+an+adjuvant+in+vaccines+produce+endotoxin&source=desktop&conversation=c95882b605df09b2838fc9&summary=1

Additionally: *Brave AI generally doesn’t mess up too badly, and I feel gives a rough idea of what a majority of search results are saying, so it is like checking Wikipedia to see what the CIA has to tell us. https://search.brave.com/search?q=pomegranate+peel+extract+promotes+toll+like+receptors&source=desktop&conversation=84dbd45a43ad256082e41c&summary=1

Pomegranate Peel and TLR Receptors

Pomegranate peel extract has been found to have various pharmacological properties, including anti-inflammatory, antimicrobial, and anticancer effects. However, there is limited information available on its specific effect on Toll-like receptors (TLRs).

Toll-like receptors are a class of proteins that play a key role in the innate immune system, recognizing pathogen-associated molecular patterns and triggering an immune response. While pomegranate peel extract has been shown to have immunomodulatory effects, its impact on TLRs is not well-documented.

Some studies suggest that pomegranate peel extract may inhibit the activation of certain TLRs, such as TLR4, reducing effects of LPS endotoxin. (Du, et al., 2019) TLR4 are involved in the recognition of lipopolysaccharides from Gram-negative bacteria. The extract’s polyphenolic compounds, including punicalagin and ellagic acid, may be responsible for this inhibitory effect. — ‘Pomegranate Peel Phytochemistry, Pharmacological Properties, Methods of Extraction, and Its Application: A Comprehensive Review,’ (Singh, et al., 2023)

• What else stimulates TLR4 production? Retinoic Acid. — ‘Retinoic Acid Facilitates Toll-Like Receptor 4 Expression to Improve Intestinal Barrier Function through Retinoic Acid Receptor Beta’. (Li, et al., 2017) Retinoid Toxicity might be additive to endotoxin risks, promoting hyperinflammation/cytokine storm/sepsis.

• How else are Gram Negative bacteria controlled by the body? By TRPV-1 or TRPA-1 ion channel signaling. (Alipizar, et al., 2017)

“…pomegranate peel polyphenols (PPPs) and their main components punicalagin (PC) and ellagic acid (EA)…"

“Our data showed that PPPs, PC, and EA inhibited LPS-induced intracellular ROS production and suppressed the mRNA and protein expression levels of TLR4 in a dose-dependent manner. Moreover, the anti-inflammatory mechanism was involved in blocking LPS-induced phosphorylation, degradation of IκB, and nuclear translocation of p65. Additionally, PPPs and PC [pomegranate peel polyphenols and punicalagin] exhibited a stronger anti-inflammatory effect than that of EA [ellagic acid].”

“Our previous studies have shown that PPPs and their main components PC and EA exert significant anti-inflammatory effects, which reduced the pro-inflammatory cytokines release by inhibiting MAPK activation. In addition, toll-like receptors (TLRs) play a crucial role in the molecular mechanisms of inflammatory processes (26). TLR4, a pattern-recognition receptor (PRR), emerges as a key player in the initiation and activation of inflammation and innate immune responses, leading to intracellular signaling cascade initiation. The study has shown that TLR4 signaling is responsible for MAPKs activation and NF-κB translocation (27). Thus, in order to further clarify the specific mechanisms of PPPs on regulating inflammatory response, and to further clarify the different efficacies among these pomegranate active components, we applied our current research.” (Du, et al., 2019)

Background information on the inflammatory process (well written, passing it forward):

“Inflammatory response plays an important role in both normal physiology and pathology (1). Prolonged inflammation can lead to many chronic diseases, including diabetes, cardiovascular disease, cancer, arthritis, and neurodegenerative diseases (2). The activation of inflammatory cascade produces various inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE₂), and pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 (3).

The production of reactive oxygen species (ROS) by phagocytic leukocytes (neutrophils, monocytes, macrophages, and eosinophils) is one of the most important characteristics in the inflammatory process. ROS activation could act as a significant and adverse participant in abnormal inflammatory diseases, and studies have shown that various antioxidants are able to prevent NF-κB activation (4, 5) and intracellular ROS generation (6).

The nuclear factor-kappa B (NF-κB) pathway has been identified as a key mediator of inflammation and serves as an important target for drug development (7). In normal cells, inactivated NF-κB is bound to inhibitor of κB (IκB) in the cytoplasm. In terms of cell stimulation, NF-κB is activated by the phosphorylation of IκB, which further leads to ubiquitination and proteasome degradation of IκB (8). The resulted free NF-κB translocates to the nucleus, where it binds to κB-binding sites in the promoter regions of target genes and induces the transcription of pro-inflammatory mediators and cytokines (9, 10).” (Du, et al., 2019)

To summarize previous research findings, Nrf2 promoters are also NF-kB inhibitors because a Clock protein is shared - one is night shift and one is day shift when our circadian cycle is in balance. So ALL Nrf2 promoting substances are pretty much also NF-kB inhibitors — and vice versa. If NF-kB is ‘On’ all the time, then healing and repair is not getting done during sleep.

Brave AI: However, more research is needed to fully understand the relationship between pomegranate peel extract and TLRs. The extract’s effects on TLRs may vary depending on the specific context, such as the type of immune cell or the presence of other immune-modulating compounds. In summary, while pomegranate peel extract has immunomodulatory properties, its specific effect on Toll-like receptors is not well-established and requires further investigation.

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“The consumption of PPE reduced amyloid plaque density, increased the expression of neurotrophin BDNF and reduced the activity of acetylcholinesterase enzyme. A reduction in lipid peroxidation and in the concentration of the pro-inflammatory cytokine TNF-α was also observed in the PPE group. No hepatic lesions were observed in animals treated with PPE. In conclusion, administration of pomegranate peel extract has neuroprotective effects involving multiple mechanisms to prevent establishment and progression of the neurodegenerative process induced by infusion with amyloid-β peptide in mice.” (Moezelle, et al., 2016)

The mice that pomegranate peel extract along with amyloid-β peptide 1-42 were less likely to not find their way out of a maze.

“Male C57Bl/6 mice were chronically infused for 35 days with amyloid-β peptide 1–42 (Aβ) or vehicle (control) using mini-osmotic pumps. Another group, also infused with Aβ, was treated with PPE (p.o.– βA+PPE, 800 mg/kg/day). Spatial memory was evaluated in the Barnes maze. Animals treated with PPE and in the control group exhibited a reduction in failure to find the escape box, a finding that was not observed in the Aβ group.” (Moezelle, et al., 2016)

Pomegranate peel may have estrogen receptor effects promoting anti-depressant effects during menopause or peri-menopause. (Valdés-Sustaita, et al., 2017)

Acetyl-L-carnitine is an amino acid that is needed as a cofactor for the mitochondrial electron transport chain: “Acetyl-L-carnitine and free carnitine, essential for brain cell energy, are found to plummet in women with cognitive decline.” - Mario Nawfal, (x.com/MarioNawfal); (Pennisi, et al., 2020); Lack of acetyl-L-carnitine was associated with more severe depression. (med.stanford.edu/news/all-news/2018/07/study-links-depression-to-low-blood-levels-of-acetyl-l-carnitine.html)

Can the gut microbiome make acetyl-L-carnitine? Maybe, it can make carnitine or carnitine-like substances, but species are not well known.

Gut Microbiome and Carnitine

Acetyl-L-carnitine is a metabolite of carnitine and supplementing with it has been found to improve gut inflammation and immune homeostasis in mice with dextran sodium sulfate-induced colitis. It is known that bacteria from the family Lachnospiraceae can produce carnitine mimics that inhibit carnitine function in the brain. (Brave AI summary/edited)

Lachnospiraceae are beneficial butyrate producing species: Lachnospiraceae - Wikipedia. Bacteria in general though, need us to eat carnitine as they need it but generally don’t make it. (Ghonimy, et al., 2018) Meat/animal protein is the main dietary source of carnitine, leaving vegans at risk of carnitine deficiency.

“Animal tissues are the main source of carnitine, especially muscles which possess about 95% of the body’s carnitine pool [6,7].” (Ghonimy, et al., 2018)

Too much carnitine or egg yolk, may be a health negative for our heart and cardiovascular system due to a metabolite, TMAO. A balance in animal products and phytonutrient and fiber rich plant foods may be the most health promoting. 3,3-dimethyl-1-butanol (DMB), found in some foods, may help reduce the amount of TMAO that is made by gut species by inhibiting a needed enzyme. (Hills, et al., 2019)

Where can we find 3,3-dimethyl-1-butanol (DMB) at a grocery store?

Answer: Cold-pressed olive oil. (Le Bras, 2018)

We need to eat a good diet for our gut microbiome, because they feed us a variety of important nutrients that they make from resistant starches and fiber in our diet including vitamin K2 and butyrate and other short chain fatty acids.

“Carnitine has vital roles in the endogenous metabolism of short chain fatty acids. It can protect and support gut microbial species, and some dietary fibers can reduce the available iron involved in the bioactivity of carnitine. There is also an antagonistic relationship between high microbial populations and carnitine bioavailability. This review shows the interactions between carnitine and gut microbial composition. It also elucidates the role of carnitine bacterial metabolism, mitochondrial function, fiber fermentability, and short chain fatty acids (SCFAs).” […]

“Carnitine (γ-trimethylamino-β-hydroxybutyric acid) is a quaternary ammonium molecule required for the transport of long-chain fatty acids (LCFAs) into the mitochondria, where β-oxidation takes place [1]. Moreover, carnitine is involved in buffering the equilibrium between acyl-CoA and CoA [2]. Carnitine can be synthesized in mammals [3], but not in bacteria, where carnitine or its immediate precursors are imported into the cells [4].” (Ghonimy, et al., 2018)

Short-chain fatty acids produced by the gut microbiome from fiber and resistant starches include butyrate, propionate, and acetate. (Ghonimy, et al., 2018) Acetate seems to help reduce appetite, risk of obesity, and improve blood sugar metabolism. (Hernández, et al., 2019)

“Carnitine can act in a direct or indirect manner with dietary fibers; this is because of the various interactions carnitine has with the gut microbiome [8]. Dietary fibers are heterogeneous and consequently have different effects on both the gut microbial community and the host animal [9,10]. The main end products of bacterial fermentation of dietary fiber are short chain fatty acids (SCFAs) [11], vitamins [10], H₂ and CO₂ [12]. Moreover, the intestinal microbiota can control various biological processes such as nutrient absorption, lipid and glucose homeostasis, and systemic inflammation [13]. SCFAs can improve the well-being of the host animal. For instance, butyrate is the preferred energy source for colonic epithelium cells [14]. Such an energy source can decrease the rate of formation of secondary bile acids from primary bile acids, and protect the host against colorectal cancer. Additionally, higher concentrations of primary bile acids have been observed in non-atherosclerosis patients than in atherosclerosis patients [15,16]. Moreover, propionate reduces the biosynthesis of cholesterol [17], providing protection against cardiovascular disease (CVD) [18]. Most acetate molecules are absorbed from the circulatory system by the liver, and used as an energy source. They are also used as a substrate to form cholesterol and long-chain fatty acids (LCFAs) [19,20].” (Ghonimy, et al., 2018)

Many chemicals of modern life, including glyphosate and pesticides, have negative effects on the gut microbiome. (Chiu, et al., 2020)

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use.

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