Dr. Subotich reversed a case of Rheumatoid Arthritis. This sent me down a rabbit hole of microbiology and pharmacology. We cover liposacharides, IL-17, gut microbiota, and how molecular mimicry is creating false endocrine signs which have so many doctors failing where Dr. Subotich is succeeding.

Notes and References

• One of the key herbs she used is is chai hu, radix bupleuri. In The Journal: BioMed Research International, 2017: in an article titled: Radix Bupleuri: A review of traditional uses, botany, phytochemistry, pharmacology, and toxicology. Yang Fude , Dong XiaoXv Et al had this to say

• “Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects.”

• I looked at the compendium of Traditional Chinese Medicine,by Li Jingwei et al., people’s medical publishing house 2004. Xiao Chai hu tang is

• 1. Anti inflammatory 

• 2. Antioxidant 

• 3. Antipyretic analgesic (Kills pain and reduces heat)

• 4.Regulates immunity 

• 5. Antibiotic 

• In Nature Reviews: Immunology Michelle G. Rooks and her partner in Crime Wendy S Garrett said, in their delicious article Gut Microbiota, Metabolites and host immunity.

• “Microbial communities, their metabolites and components are not only necessary for immune homeostasis, they also influence the susceptibility of the host to many immune-mediated diseases and disorders.”

• So if you have an auto immune disorder it pays to look at the guts.

• In the March 15th 2016 issue of Cell Press to read what Pawan Kumar, Leticia Monin, et al found that Intestinal interleukin-17 receptor signaling controls gut microbiota and autoimmune inflammation. What is so special about interleukin-17? Interleukin-17 (IL-17) and IL-17 receptor (IL-17R) signaling are essential for regulating mucosal host defense against many invading pathogens. Commensal bacteria, especially segmented filamentous bacteria (SFB), are a crucial factor that drives T helper 17 (Th17) cell development in the gastrointestinal tract.

• Does anything in Wind aka xiao chai hu + san ren tang influence this?

• According to Xue yang, Ji Yang, and Hejian Zou, A component of Huang qin, baicalin inhibits IL-17 mediated joint inflammation in Murine Adjuvant-Induced Arthritis

• Okay, so case closed. Baicalin cures RA right?

• Well, no. It will drop inflammation and has this effect, but we need to look at cultivating the garden as a whole to have long term immune regulation. Okay so is there anything in the way of eating some vegetables and calling it good? According to Aila J Ahola et al:

• Lipopolysaccharides (LPS), also frequently called endotoxins, are lipid-soluble outer-membrane components of Gram-negative bacteria. …the bacteria colonized in the intestinal tract are a major source of LPS in humans. Importantly, LPS may be translocated from the intestine into the systemic circulation. During the prandial state, for example, the lipid regions of the LPS particle are incorporated into the forming chylomicrons, thereby enabling its absorption. The paracellular translocation of LPS, on the other hand, may be enhanced upon impairment of the integrity of the mucosal epithelial barrier.

• The nastier your diet, the more of these endotoxins are kicking around in the gut and they get into your blood stream. 

• Fewer Bacteroidetes and more Firmicutes seem to characterize the gut microbiota of obese people as compared with that of lean individuals.

• LPSs can cause a condition of “metabolic endotoxemia” characterized by low-grade inflammation, insulin resistance, and augmented cardiovascular risk. LPSs are a powerful trigger for the innate immune system response.

• Increase in intestinal tight junctions and increase intestinal permeability. This creates endotoxemia.

• Endotoxemia is associated with stress, obesity, and auto immune diseases. This appears to rise with high fat modern diets, yet fat isn't completely to blame.

• High fat diets, but not ketogenic increases liposacharides and endotoxins

• The modern diet with preservatives, pesticides, and heavy fat content causes excess liposacharides. These cause internal chaos.

• Liposacharides have risen in the US diet along with obesity and prevalence of diabetes. Now their prevalence is spiking in China as well. The shift from a plant based diet been associated with increased diabetes, lowered fertility, and autoimmune disorders.

• Rice and vegetables was associated with more with prevotella bacteria while bacteroides is associated with higher animal fats. The relative ratios of gut bacteria may be useful in the near future for diagnosing complex chronic diseases associated with variations in gut microbiota.

• This shift in gut bacteria and its related pattern of diseases is starting to be called an “Enterotype” This may be useful as a general categorization in the way that traditional concepts of yin bodies and yang bodies are or the short hand found in Greco-Roman concepts of the 4 humours with Choleric, meloncholic, sanguine or phlegmatic. These were essentially used to find a person's enterotype and even their temperament. Its important to remember that the enterotype can change relatively quickly, but even as it does that won't immediately alleviate the systemic stresses or advantages caused by having a given enterotype.

• Even when this does shift we need to remember that this does not necessarily cause an immediate cleansing of endotoxins that have already seeped into the blood.

• There is also a matter of damage caused by inflammation and imbalances already caused in the endocrine system. This is extra challenging because liposacharides can mimic hormones through a process called "molecular mimicry."

• Molecular mimicry of host structures by the saccharide portion of lipopolysaccharides (LPS) of the gastrointestinal pathogens Campylobacter jejuni and Helicobacter pylori is thought to be associated with the development of autoimmune sequelae.

• This is why an extract of an herb won’t save the day. Its essential to carefully clean the blood restore gut harmony, and remove the molecular mimicry that is making the body look artificially deficient. In this day and age with the modern diet blaming the thyroid, or a deficiency can no longer by our base assumption. 

• Liposacharides also influence the entire body as they throw off gasotransmitter balance and their relationship to healthy gut bacteria. This further compromises the immuno-endocrine system.

• We must look at what is interfering and remove it. Dr. Jin Zhao DTCM Ph.D has long stressed that modern people are not the same as ancient Chinese and we must adapt accordingly. His focus on removing "hidden damp" was a big inspiration for Dr. Subotich. He was the first to tell me in details about dampness blocking the san jiao, collaterals, and kidney function. His observations are also echoed by modern epidemiology regarding liposacharides and molecular mimicry. This should change our perspective when it comes to diagnosis and treatment. We should first and foremost look at the influences of endotoxins and liposacharies because these are the great challenges of our age. Dr. Subotich’s was able to rapidly alleviate RA symptoms and biomarkers by truly getting to the root cause and helping the patient to cultivate a garden within.

References:

1.Yang, Fude, et al. "Radix Bupleuri: a review of traditional uses, botany, phytochemistry, pharmacology, and toxicology." BioMed research international 2017 (2017).
2. Li Jingwei and other editors. Compendium of Traditional Chinese Medicine - 2nd Edition [M]. Beijing: People's Medical Publishing House, 2004:李经纬等主编.中医大词典——2版[M].北京：人民卫生出版社，2004：
3.Rooks, Michelle G., and Wendy S. Garrett. "Gut microbiota, metabolites and host immunity." Nature Reviews Immunology 16.6 (2016): 341.
4. Kumar, Pawan, et al. "Intestinal interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation." Immunity 44.3 (2016): 659-671.
5. Yang, Xue, Ji Yang, and Hejian Zou. "Baicalin inhibits IL-17-mediated joint inflammation in murine adjuvant-induced arthritis." Clinical and Developmental Immunology 2013 (2013).
6. Ahola, Aila J., et al. "Dietary patterns reflecting healthy food choices are associated with lower serum LPS activity." Scientific Reports 7.1 (2017): 6511.
7. Manco, Melania, Lorenza Putignani, and Gian Franco Bottazzo. "Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk." Endocrine reviews 31.6 (2010): 817-844.
8. Guo, Shuhong, et al. "Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14." The American journal of pathology 182.2 (2013): 375-387.
9. de Punder, Karin, and Leo Pruimboom. "Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability." Frontiers in immunology 6 (2015): 223.
10. Pendyala, Swaroop, Jeanne M. Walker, and Peter R. Holt. "A high-fat diet is associated with endotoxemia that originates from the gut." Gastroenterology 142.5 (2012): 1100-1101.
11. Wu, Gary D., et al. "Linking long-term dietary patterns with gut microbial enterotypes." Science 334.6052 (2011): 105-108.
12. Moran, A. P., and M. M. Prendergast. "Molecular mimicry in Campylobacter jejuni and Helicobacter pylori lipopolysaccharides: contribution of gastrointestinal infections to autoimmunity." Journal of autoimmunity 16.3 (2001): 241-256.