Gut Permeability = Why We Are Sick and Fat?
Photo credit: Gravitz. Nature, 2012.
Photo credit: Gravitz. Nature, 2012.
Microbial Influence
We co-evolved with the microbes in our gut to escape pathogens, parasites, predation and starvation (emo, nutritional, mental, etc), whilst hunting for palatable food, prey and partners. (Isn't your partner palatable?) Simultaneously we enjoy all benefits that our co-existing gut microanimalia provide -- digestion of indigestible fibers/resistant starches, butyrate/short-chain-fatty-acids, neuroendocrine modulation, boosted immunity and tolerance, to name only a few. They weigh 1-2 kg in our daily feces, contribute to massive biofilms (slime communities) in our guts and sinuses, and line every interface where human interiors meet exteriors. The microbiota are not a small forgotten organ any longer.
It has been realized for decades that 70-80% of human immune cells are in the GI system; I believe however a large proportion (70-80%??) of our total immune system IS the gut microbiota. The # of genes collectively in a microbiome are 150 times larger than the genome of their host human. Besides digestion and metabolism, our microbiota perform far more than we perhaps currently understand in cross-talking with the immune system, its maturation and role in homeostasis and energy balance.
Dysbiosis and Intestinal Permeability as Origins of Disease
Modified: GREER, MORGUN, AND SHULZHENKO, 2013
Emerging data like the study reviewed here showing the rodent T1DM disease model was averted by the presence of a soil based microbial strain known as SFB (segmented filamentous bacteria; genus Arthromitus) confirm and highlight the vital role played by commensal gut species in our immune system. I find it notable that the hearty and robust spore-forming ones that originate from dirt sources are producing some of the most interesting scientific findings since we co-evolved with ancient dirt for millenia.
Since the vast majority of microbial fermentation occurs in the caecum, appendix, and remainder of the large colon in humans, our small intestines are nearly sterile and absent of bacteria and fungi except at the end (ileum) where commensal species take residence. Studies on TH17, one of the important arms of the immune system, show that no TH17 cells will appear in the small intestines until commensal microbes inhabit the area. Germ-free rodents will miss an entire arm of the immune system until colonization with introduction of a SFB-containing commensals.
Toxic and Germ-free Fetuses, Babies, Children and Adults
The collective status of our guts pretty much reflects the status of our current macroecological niche for humans I think... massively insolvent, blatantly bereft of vision, and irrevocably impoverished. In China I read everyday of villages blighted with river and ground water poisoning by illegal corporate dumping of industrial waste. Post-modern towns are plaqued with leagues of cadium or arsenic poisoned children. Even locally in our neighborhood Pudong, Shanghai, lead toxicity was detected in many children living near manufacturing plants called Johnson Controls International Battery Inc. In the USA, coal burning which provides 30-50% of current energy demands has tainted the air/water/soil and caused mercury and arsenic accumulation in marshes and wetlands and the flora and fauna that reside there. Birds no long sing, woo, mate or care for their young appropriately. Mercury-toxic birds are literally the canaries in our toxic macroecological niche. What about human canaries, our children? I think epidemic rises in toxin related diseases are accurate and reliable reflections because toxins disrupt the intestines and microbiotia:
--AUTISM (1:50 currently compared with 15 years ago 1:10,000)
--CELIAC DISEASE (6.4-fold increase in 20 yrs, Scotland)?
--OBESITY AND METABOLIC DISEASES
Our hyper-hygiene and dirt-avoidance culture extends to the over utilization of potent broad spectrum antibiotics piled into the feed of poultry, pigs, cattle dairy/egg production and in modern conventional healthcare. In the a new study by Stanford researchers, the mechanism for why pathogenic gut strains invade after a single course of antiobiotics has been illuminated. Pathogenic strains C. diff and S. typhi are shown to take advantage of the abundant sialic acid and fucose sugars that are left after antibiotic extermination of 'good' commensal gut flora. The researchers also report in a model where C. diff and S. typhi were genetically altered to fail to utilize sialic acid, expansion by the pathogens was impaired.
Modern Obesity: Inflammation, Intestinal Permeability
Modified: GREER, MORGUN, AND SHULZHENKO, 2013
Modified: GREER, MORGUN, AND SHULZHENKO, 2013
Toxins Delete the Good Microflora, Stimulate the Bad Microflora
When I had toxicity from gluten, oral birth control, antibiotic overutilization, thimerosal vaccines (tetanus, annual flu, blah blah blah), titanium and mercury amalgams, I had no idea that each and every one of these factors promote pathogenic gut flora, vitamin B12 deficiency, and kill or inhibit beneficial 'good' gut flora.
Did these toxic factors make me fat? Absolutely.
It was not [CALORIES IN = CALORIES OUT].
Fermented Fiber Produces SCFA Which Activate Immunomodulating G-Protein Receptors (GPRs): In pubmed studies, each of the above toxic factors are highly linked to gut dysbiosis and obesity. Stopping or eliminating each of the above eliminated subsequent inflammation and obesity for me (combined with Asian paleo + exercise). Understanding the human superorganism anatomy and physiology gives pause to recognize the role the gut flora had in the ups/downs of my health over the decades. Recall about ~10% of total energy expenditures are estimated to be supplied by hindgut fermentation that occurs in the caecum and colon (versus 20-30% for other omnivores). Production of SCFA, small chain fatty acids (acetate, proprionate, butyrate), and other downstream metabolite byproducts (succinate) bind receptors known as FFA2/FFA3 and SUCNR1, respectively, that control and regulate inflammation (TNF, interleukins, NFkB) and immune function. Metabolite sensing occurs through these G-protein receptors much like how omega-3 EPA+DHA bind 'omega-3 receptors' GPR120 and elicit their anti-inflammatory and immunomodulating actions. FFA2 (GPR41) receptors are found in enteroendocrine cells, adipocytes, neutrophils, eosinophils and pancreatic islets; and FFA3 (GPR43), enteroendocrine cells, pancreatic islets and sympathetic ganglia.
I believe these effects on GPRs design a metabolic flux which tunes metabolism UP and DOWN based on the messages that our food, movement, minds, and microbiota co-create. My new formula for comprehending energy balance might be...
Calories In = Calories Out (MICROBIOTA) + Calories Out (HUMAN) + [HEAT]*FLUXXX
(SUPERORGANISM)
Main pathways of energy metabolism for dietary fats, fiber and carbohydrates
Fermentation of indigestible fiber and resistant starch to SCFA
Photo credit: Nature Reviews
Diabesity: Recall pesticides are highly associated with Diabesity.... Coming to China actually forced our family to go as much as we can 100% organic and non-GMO (although all labels are dubious). In the States, when my in-laws cooked for our family I didn't have control (eg they were too cheap to buy organic). In the USA, the organic label is also dubious to me but for the most part it's way way way better than in China.
MonSATAN GMO Seeds
Round Up Ready Crops (glyphosate) -- Alfalfa, Canola,
Corn, Cotton, Soybean, Sugarbeets
Round Up Ready Crops (glyphosate) -- Alfalfa, Canola,
Corn, Cotton, Soybean, Sugarbeets
Recent research demonstrated that glyphosate (Round-Up Ready) allows growth of pathogens and kills the friendlies in studies of intestinal microecology in chickens. EWP studies show babies and people's toxomes contain on average 200-300 known carcinogens, chemicals, heavy metals and pesticides. 100% of all participants (n=9) in the EWG #1 Commonweal Study had metabolites of organophosphate pesticides, and 55% -- organochlorine pesticides. Do pesticides in our food and contaminating our water/soil disrupting our gut? I would say emphatically yes. In China, Round Up Ready sweet corn is mega popular. China imports that and millions of metric tons of GMO cotton, soy beans, corn, rapeseed and sugar beet.
For several years now, commercialized GM cotton, papaya, sweet pepper, tomato, poplar, and petunia have been grown without public awareness. One journalist reports that 90% of China grown cotton is GMO cotton (2008). The report also found 40 billion tons of soybeans were imported in 2009. GMO Soy likely goes into thousands of Chinese products here -- (rancid) cooking oil, animal/poultry/aquaculture feed, tofu, soy milk, soy sauce, etc. 40 BILLION TONS OF GMO. Asians love their soy OY OY OY... It's truly the land of sarcopenia and soy, no? Is this behind the epidemic of obesity and diabetes in China among children, adults and elderly alike?
Chinese companies offer a ton of Glyphosate (Round Up Ready)
Source: Alibaba
Horizontal Gene Transfer. Does horizontal gene transfer (HGT) between DNA from consumed GMO corn and corn products to our gut microbiota occur? Another emphatic YES. How do you reverse it if your microbiota is transformed? I wish I knew... Bacteria and fungi live in biofilms and exchange DNA within the matrix. Like a meme gone viral. Evidence for both DNA and lectin proteins from GMO Bt corn has been found in animals and humans that consume Bt corn. The DNA was found to survive and persist for a long time in the gut/rumen.
Photo credit: Heritage J. Nature, 2004.
I talked about Bt corn previously here: 50 Shades of F*ckd and Cancer. Every pesticide corporation has a GMO Bt corn brand. Bt is a lectin (like gluten) and disrupts intestinal epithelium in susceptible victims which can lead to gut dysbiosis and/or death. It was very effective pesticide in the beginning.
Rootworms and other pests have rapidly shown field resistance to nearly every brand -- Syngenta's Agrisure and Monsatan's YieldGuard. Dupont/Dow's Herculex has not as much, therefore Monsatan has reported they are planning to incorporate Herculex to synthesize TWO TOXINS into their new SmartStax corn -- in an attempt to overcome inherent field resistance. GMO is brilliant, no?
Unfortunately significant Bt lectin protein has been detected in fetus, pregnant women and non-pregnant women in already one clinical trial. Can we look forward to double the toxins next? Can we afford to because we are kinda 50 Shades of F*ckd already...
Boobies and Breastmilk Microbiota
Symbionts Are Everywhere: Our microvilli produce siliac acid and fucose (9- and 6-carbon sugars) at the tips for commensal gut flora to feast and graze on. I call it 'pharming the gut'. Again, like much of life on earth -- hominids, insects, fish, frogs, mammals -- we have evolved with gut symbionts, encouraging them to take residence and producing incentives for their maintenance. We should strive to avoid screwing our symbionts...
The baby-mother relationship is another example of the ultimate symbiosis.
Photo credit: Fernandez L et al, 2013.
Initially breastmilk was considered sterile but like many things in science, this was inaccurate. Colostrum contains over 700 live organisms (European Society of Neurogastroenterology and Motility: Gut Microbiota Worldwatch). Are these important? Why? Lysates of strains such as Lactobacillus and Bifodobacter have been shown to tighten up the intestinal tight junctions. Several strains in probiotics have been shown to be associated reduced mortality in NICU settings and against often fatal necrotizing enteric colitis.
Although babies are born with leaky guts to accomodate mothers' large proteins direct access into blood and lymph circulation (immunoglobulins, IgM), they appear to get a lot of help from natural commensals to switch and develop intestinal impermeability.
Photo credit: Cabrera-Rubio et al, 2012.
Where does mammary microflora originate from? Some researchers hypothesize there is a special conduit that transfers gut flora to the mammary glands, an 'entero-mammary pathway'. Lymph circulation? It is unknown and not entirely elucidated. Researchers looked at microbiota in breast milk (at 0 mon/colostrum, 1mon and 6 months), different areas of the mother's body and compared flora between elective C-section and vaginal/non-elective C-sections. Breastmilk from C-section moms resembles mouth/oral and skin flora; whereas, breastmilk from moms who went through vaginal birth or some modicum of vaginal delivery that ended in non-elective C-section (that was me) showed flora that matched the gut and feces. Birth does something to make proper milk. "The fact that the milk microbiome of mothers who gave birth by nonelective cesarean section had a normal microbial composition that was comparable to that of breast milk from mothers who delivered vaginally suggests that physiologic (eg, hormonal) changes produced in the mother during the labor process may influence the composition of the bacterial community."
Are Toxins + Early Post-Natal Gluten Exposure J*cking Us? Gluten peptides also traverse and are dispensed to the baby during lactation from a gluten-eating moms. Does this contribute to the gargantuan rise in celiac and autism? Babies are born sterile but breastmilk has over 700 organisms to colonize and modulate intestinal permeability. If babies are born under circumstances where mom doesn't provide the needed commensal gut bacteria (overweight/obese mom (me, again), elective C-section, antibiotics at birth), it could be plausible IMHO that peptides like gluten in mother's milk will cross directly into the baby's blood circulation without the 'blockage' or junction tightening effect from missing commensals. Gluten on its own also opens zonulin, further impairing, I suspect, a baby's gut permeability.
We may need commensal gut critters not only for immunity but also for chelation and elimination of modern, industrial heavy metals. Studies show several soil-based bacteria microbes chelate and bind toxic metals.
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