Tuesday, September 24, 2013

Feeding the Microbiota: Non-Starch Polysaccharides (NSP), Resistant Starch (RS) and Mucous


"During the co-evolution of man and microbes, the human intestinal tract is colonised by some thousand species of bacteria. Gut borne microbes outnumber the total of body tissue cells by a factor of ten. Recent metagenomics analysis of the human gut microbiota has revealed the presence of some 3.3 million genes, as compared to the mere 23 thousand genes present in the cells of the human body tissues."

--Rijkers et al, Gut Microbiota in health and disease: a personalised summary of 
the 3rth workshop

Everything Our Microanimalia Do For Us
How Shall We FEED THEM?

Seed, Weed and Feed the GUT

I've talked already about many ways to seed the gut (fermented foods, SBO probiotics, dirt, etc) to complement the existing microbiota and weed the gut -- removing toxins, mercury, pathogenic overgrowth, parasites and worms.  How should we properly water and feed the gut?

The primary foods are fiber, mucous and starch that resists small intestine digestion. If the gut is diseased, crowding out pathogens and removing parasites is also important. If the microbiota lacks diversity, then diversity needs to be cultivated and nurtured.  Studies show the obese, inflamed, autistic and heart diseased lack microbiota diversity of species and phyla.

Feeding and nourishing the microbiota isn't a special skill... our ancestors thrived and survived in special microecological as well as macroecological niches... and so did the gut microbes.  How did ancestrally derived foods benefit the microbes and what do they specifically provide for us?  Do we rely on them for immunity? For activation of important immune factors (glutathione, our #1 master antioxidant)?  For activation of plant-derived antioxidants like lignans, etc?  For removal of toxic and carcinogenic bile acids?  To balance the steroid hormone pool?

Yes to all.

I like ancestral diets. They must've worked I figured because we are here...

Being Asian I enjoy starches and after regaining insulin sensitivity (after being 50 lbs overfat), I burn starches adequately during glycolytic activity. With VLC/ketosis, I had cortisol dysregulation and to heal metabolism fully I had to eat carbs regularly. Being previously metabolically broken and still recovering from some toxicity (heavy metals, contraceptive endocrine disruption), however, I don't overdo the starches because I'll notice that I regain bodyfat mega fast.  Typically intake may be 1/4 of plate at most meals).

Our family eat certain starches regularly -- carrots, radishes, steamed pumpkin, bamboo shoots, fermented sauerkraut/carrots/radishes, tubers (yellow, purple, white, small potatoes, yams), flours (tapioca, sweet potato) and soaked grains/seeds (psyllium, millet, sorghum, black sesame, rice (purple, brown, white, glutinous)).   The variety depends on what is in season and carried by the organic farms -- Mahota, FIELDS, BioFarm/Cityshop, etc.  All the above contain both fiber and resistant starches (RS) which the microbiota feed on.  Ultimately, both types of microbial food benefit us on many levels.

In fact some studies show synergism when both fiber and RS are consumed together compared to fiber alone (beta-glucan) or RS alone for insulin and glucose reduction and regulation. Behall, et al:  synergism -- MEN and WOMEN. Below is the outcomes from the female study examing the impact on BG and insulin with intake of beta-glucan + RS. The levels of both were modulated low v. high and vice versa. Higher beta-glucan and higher RS produced the most marked improvements in metabolism. High amounts of either were satisfactory as well (see yellow/insulin,  orange/glucose lines and green circles).  Low amounts of either fiber or RS, not nearly as wonderful metabolic outcomes in this study.

Beta-glucan is a special soluble fiber (NSP)-- it's not made by mammals. It's found in yeast cell walls, whole grains, and mushrooms.  It's been shown to not only affect the microbiota but also improve immune function, wound healing, metabolic dysregulation, cancer/tumour sizes, and inflammation.  A recent study tracked the fate of beta-glucan in the gut and immune lymphoid tissues.  Researchers found "these large -1,3-glucans were taken up by gastrointestinal macrophages and shuttled to reticuloendothelial tissues and bone marrow. Within the marrow, the macrophages degraded the -1,3-glucan and secreted small soluble biologically active fragments that bound to CR3 of mature bone marrow granulocytes. Once recruited from the bone marrow by an inflammatory stimulus, these granulocytes with -1,3-glucan-primed CR3 could kill iC3b-coated tumor cells."

Resistant starch (RS) is found to be quite as plentiful as beta-glucan and plant fibers however cooking breaks it down to a form that we can digest (enzymatic, mastication, acidic).  The amount remaining in a food that escapes our digestive juices varies by many factors -- species, maturity of the plant, cooking/cooling methods, food acidity, to name just a few. RS is different from beta-glucan and fiber due to its tightly bound double helical glucose polymer structure.  Yes it is coiled up like DNA....  Solubilization in cooking water 'releases' the starches into a gelatin matrix which our spit amylases and pancreatic carb-ases can breakdown to glucose for absorption in the stomach and small intestine.  Any undigested amounts enter the caecum and colon.  The amount of SFCA produced upon caecal and colon fermentation varies as well depending on an individuals microbiota species, large intestine health status, etc.

The average intake of RS in China is 14.9 g/day from wheat, rice and starch products (mung bean, sweet potato noodles); compared with average USA 3-8 g/day intake it is about 2 to 5 fold increased. However, I don't think this holds true any longer for Chinese urban dwellers. When my parents grew up in a small rural village in Taiwan (with pigs and 'home organic' e.g. subsistence farms), they were poor and only ate potatoes, yams, mung beans, rice, and vegetables with very scarce meat/fish/pork belly or chicken or eggs. I believe their childhood intake fiber and RS intake were far more than currently, if not triple or quadruple.

Combined with veggies, most people's diets contain a mix of carbohydrates: rapid digesting (simple sugars, disaccharides), slow digesting (complex carbohydrates), nonstarch polysaccharides (FIBER = b-glucan, xylan, glycan, gums, pectin, mucin, cellulose, hemi-cellulose etc), and resistant starches (RS) to fuel both our human cells and the microbiota.  Our microbiota in the large intestines will eat and ferment fiber, RS, and the mucous produced in the protective layer of the gut.

Most Dietary Starches Contain Both b-Glucan or other soluble fiber + RS
Source: Behall et al

For SIBO and intestinal permeability, it's actually healing to minimize fermentation if it is occurring pathogically in the small intestines... where it shouldn't be.  The surface of the small intestines is not designed to support extensive networks of microbial growth which requires thick mucous.  The integrity of the small intestines can easily be compromised and fail to serve its function (digestion and absorption) when inappropriate growth manages to perpetuate whether it's 'good' v 'pathogenic' bacteria, yeasts or mycobacteria or parasites/worms.

The ONE (optimal nutri eval) is one of the best tools to measure the microbial/fungal metabolic by-products in the urine by opportunistic and pathogenic species in the small intestines.  The GDX/Metametrix GI function stool test is unique to identify microbial overgrowth, dysbiosis, pancreatic digestive enzyme capacity, small intestinal fat/fiber/protein malabsorption, and parasites/worms as well as assess microbial sensitivity to herbal and pharmaceutical antimicrobials.

Diet absolutely shifts bacterial communities in the gut ecology -- simple sugars lowers the good, raises the bad. More fiber and RS both raise the good (in Bacteroidetes -- Prevotella, etc), lowers the bad (in Firmicutes -- virulent strains of clostridas, E. coli's, enterococci, streps).  This is borne out in pig, children and human studies.  Flint et al do a great review here which includes a raffinose study (fiber from legumes) that enriched and ↑ F. prausnitzii, Bifidobacterium spp.  Like many of the good gut flora, Bifidobacter tightens up the intestinal tight junctions as super tight as a nun's **ss, which is enteroproctive and immunoprotective again gastroenteritis, intestinal permeability and necrotizing enterocolitis in trials. Guess what?  Magnesium deficiency compromises Bifidobacter and intestinal permeability (or which came first?).  Bifido appears to enjoy magnesium. In rodent studies fed a mag-deficient diet, intestinal permeability and quantitative changes to cecal bifidobacteria were associated.

My kids and I have scr*wed up Bifido (not bad but could be far better -- 3.2; Brent Pottenger's Bifodobacter is over 20% more and rocks at 3.9)... and we have low mag...  Brent has also has had zero cavities and therefore zero mercury amalgams.  Perhaps my fam and I need to forage us  some raw unpasteurized human breastmilk because it is enriched with Bifido?

Below is a human study n=10 on the microbiota shifts comparing RS2 and RS4 intakes (55 grams/day x3wks, then 2 wk washout).  Even among resistant starches, there is selective species enrichment.

The authors state in the results:  "Ten human subjects consumed crackers for three weeks each containing either RS2, RS4, or native starch in a double-blind, crossover design. Multiplex sequencing of 16S rRNA tags revealed that both types of RS induced several significant compositional alterations in the fecal microbial populations, with differential effects on community structure. RS4 but not RS2 induced phylum-level changes, significantly increasing Actinobacteria and Bacteroidetes (+++)while decreasing Firmicutes(-). At the species level, the changes evoked by RS4 were increases in Bifidobacterium  adolescentis and Parabacteroides distasonis, while RS2 significantly raised the proportions of  Ruminococcus bromii and Eubacterium rectale when compared to RS4. The population shifts caused by RS4 were numerically substantial for several taxa, leading for example, to a ten-fold increase in bifidobacteria in three of the subjects, enriching them to 18–30% of the fecal microbial community. The responses to RS and their magnitudes varied between individuals, and they were reversible and tightly associated with the consumption of RS."

Similar enrichment in enterocytes occurred in a rat weanling study feeding either basal diet or RS 5% for 28 days. I like this study because it demonstrated increased glutathione (our #1 master antioxidant; I have a GSTT1 deletion so mine is mildly compromised) by over 2-fold and improved pancreatic elastase secretion (digestive enzymes) in the RS fed groups.  [***Personally I eshew all rat studies unless they're vegetarian studies because (1) rats don't have a gallbladder and (2) they're not as omnivorous as humans or pigs so the data is incomparable, particularly the (ludicrous) meat/colon ca/nitrosamine studies.]

Shifting Microbiota Communities: GI Fx Stool Test and Optimal Nutri Eval (ONE)

Brent Pottenger's case:  Recall his Prevotella, Bacteroidetes and Firmicutes are quite stunning and no biomarkers of dysbiosis.  He has likely very little mercury (no history of cavities). His diet: near carnivory, fermented full fat Greek + some veggies both raw/cook (per Pottenger's cats).  The microbiota sequencing reveals a beautiful display of healthy guts.  Previously he c/o acne and migraines which are signs of SIBO and intestinal permeability.

My case: The Prevotella, Bacteroidetes and Firmicutes (2013) are impressively improved and robust compared with the initial 2011 when I had CFS, fogginess, fraility (sarcopenia), rank mood, and on/off body fat.  The SIBO is gone except for residual dysbiotic biomarkers from a parasite and Morganella. [yes wtf I dunno where the origin was but my children also have pathogenic overgrowth or parasites but we all different. I suspect I got it from one the irresistable poopers, see below]

Would you like to do a GI fx stool test and see your microbiota and do a ONE to evaluate nutrient deficiencies, dysbiotic markers and 8OHdG (DNA damage)?  Let me know and show me!  (Cost $99 and $129, respectively, plus admin fee $50).  Let's conduct paleo gut experiments.

What had I done?
--for two years
  • gluten free, casein free, exercise/yoga (some barefoot on soil/lawn)
  • removed mercury, gold, titanium parts and oral chelation on/off
  • sleep, adrenal/gut support, antioxidants incl pycnogenol, omega-3, minerals
  • Prescript Assist, FloraMend
  • whole food diet (rainbow tubers, veggies, organic meat, lard/ghee)
  • fermented pao cai, Beijing radishes, carrots

--for two months prior to the GI fx stool test
  • Seed: Raw unpasteruized sauerkraut at nearly every meal and drank the brine, SBO probiotics
  • Weed: charcoal and bentonite clay; removed gut irritants (alcohol -- studies here and here)
  • Feed: Kraut and fiber rich foods (basmati rice, vegetables, potatoes, etc)

Energy Flux and Metabolism in Superorganisms

I consider this formula for energy flux:

Calories In (SUPERORGANISM) = Calories Out (MICROBIOTA) + Calories Out (HUMAN) + HEAT*Fluxxx

Rapid and slow digesting starches (RDS, SDS) impact blood sugars and insulin sensitivity by raising BG. The effect on insulin sensitivity and how they burn fat in the mitochondria actually depends on the individual, their insulin sensitivity and the carb/glycemic load.  See Major Paleo De-Mything.

On the other hand, insoluble or soluble fiber and RS do not raise insulin or blood sugars. In fact fiber and RS have been shown in several trials to behave like protein and omega-3 fats by raising insulin sensivity.  Both fiber and RS naturally have glycemic indices of 'zero', 'bulk' up food, increasing fecal transmit time as well as fecal microbial biomass. Combined with digestible carbs, RS and fiber both tend to prevent spiking of glucoses, thus blunting the effects of high GI (glycemic index) foods and sweets. Both fiber and RS definitely lower inflammation but appear to do so via routes which are intimately tied to the microbiota.

Role of the Gut Microbiota in Nutrition and Health

The mouth and stomach digest ~10% of our carbs and the rest 90% is digested in the small intestines if all is functioning (pancreas, gallbladder, oral amylases, GI acidity, microvilli brush border enzymes, pepsin secretion, bile, peristalsis).  What escapes small intestinal degradation is later fermented by the microbiota in the large intestines (caecum, appendix, colon) to volatile organic acids, known as short chain fats -- acetate, proprionate and butyrate.  Although microbial byproducts provide some fuel to us  and the local enterocytes in the gut ecosystem (~10% of our total energy requirements compared with ~30% in other omnivores), actually much of the butyrate and other SCFA goes to provide energy to the microbiota . See above diagram 'Fermentation -- energy for bacterial growth'.  From my reading this amount varies. The SCFA collected at the colon depends on inflammation, IBD status, diabetic v. nondiabetic, etc.  I think it reflects SIBO and intestinal permeability factors which affect the microbiota.

SCFA play a role in the immune system and metabolic pathways by as binding fat-sensor receptors such as PPAR alpha, gamma, delta and GPR41/43.

How we chew the food and shear the particle sizes of resistant starch granules determines how much may be broken down in the small intestines. The first, top diagram above shows how digestive amylases 'etch' granules of resistant starches recovered in the intestines.  Food preparation also transforms the digestibility, crosslinks and polymerization of the starch matrix.  Longer heat, higher boiling/gelatinization, and maturity of the plant are all factors that predispose to higher digestibility and potential blood sugar impacts.   Cooling the starch and adding acidity (lemon, vinegar, fermentation) all lower small intestine digestibility by changing the coagulation of starches and protecting the starch granules from enzymatic degradation. Both refridgeration and autoclaving (high moist heat) polymerize the starch chains and raise RS.

So certain foods will have more RS as a result of food prep compared to the original food:
Fried rice or 'al dente' rice versus rice boiled in large volumes of water
Cold chinese rice ball snack rolled in lard/oil and seaweed versus warm steamed white rice
Sushi rice (room temp rice, sweetener +vinegar) versus warm steamed white rice
German cold potato salad with vinegar versus a boiled LARGE American monoculture GMO potato
Whole grain wheat pasta versus overboiled white pasta

Fermentation breaks down RS
Boiled poi (more) vv. Fermented poi (less)
Unfermented cooked rice v. Fermented Indian dosa rice or idli (less)

Autoclaving polymerizes amylose so raises RS
Processed (heating/reheating process) Uncle Ben's rice (but beware of the endocrine disrupting plastic it's encased in) v. freshly cooked long grain rice (less)

Evolution of RS

The amount of resistant starch appears to me to be related to the amount of protein in the tuber or grain/seed, on cursory review. I've tried to dig further but can't find anything.  The food sources which appear to have the most RS are the starch containing foods with intact cell walls and higher protein content legumes (9.5-11.1% dal, lentils, beans), whole grains (4.5-6%), or complete proteins (2% potato; 4.8-5.9% processed non-modified PS; steamed/cooled potato 31% and roasted/cooled potato 52.5%).  Perhaps amylose and other RS protect the peptides embedded in the starch matrix for tuber and grain/seed winter storage to buffer the Ice Age chill? Sprouting and germinating grains/seeds raise protein and nutritional content, but lowers RS.  Additionally, fermentation of starches is a trade-off -- fermentation lowers RS but raises protein/vitamin content.

Saturday, September 21, 2013

Why We Are Sick and Fat: Calories In (SUPERORGANISM) = Calories Out (MICROBIOTA) + Calories Out (HUMAN) + HEAT*Fluxxx

Gut Permeability = Why We Are Sick and Fat?
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

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)?

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

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.


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

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.

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.

Babies receive everything from mom -- life, love, heat, immunity (IgM), food, and water.  It's one of the most symbiotic relationships on earth outside of pair-bonded couples and tight knit families and communities. The baby is born sterile with no immune system, relying on mother's immunoglobulins to handle environmental viral or microbial assaults.  If advanced hominids and other mammals outsourced 70-80% of its immune system to gut microbiota, what does the timeline for acquisition of gut flora look like in babies?

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."

Another finding from this study was 'Milk from obese mothers tended to contain a different and less diverse bacterial community compared with milk from normal weight mothers.'

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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Sunday, September 15, 2013

My n=1 Pre- and Post-Microbiome, Digestion, SCFA, Fat Malabsorption, Pancreatic Insufficiency, Leanness F:B Ratio, and How I Healed SIBO and the Gut-HPA-Gonad Axis

Functional Lab Testing: GI Effects Stool Test (GI Fx)

There are several tests I think everyone should get if they are suffering from any chronic conditions, cancer, or inflammatory condition. One is the Metametrix/GDX GI Fx Stool test.  This is one of the most advanced tests that accurately, reliably and thoroughly evaluates the entire intestinal tract and the gut microbiota.

Using PCR sequencing on the 16S ribosome of microbial species and parasites, it accurately assesses both our microbiome (genetics) and those of any parasites.  The old 200-year technology of O&P x3 (ova and parasite) from 3 samplings of stool should be over; to achieve a positive identification, one must rely on the luck and fortune of the microbiologist viewing the smear on the slide to observe a parasite glide by or tiny ova like needles in a haystack.  I believe stool cultures are equally primitive technology and unreliable. Over 80-90% of stool microbes are obligate anaerobes and/or symbionts which are difficult or impossible to grow in culture or without their neighboring microbes necessary to sustain life.

***Read the Metametrix/GDX Interpretative Guide for the GI Fx Stool Test: HERE.

Example of a Super Super-Organism: B. Pottenger

My m=1 Microbiome: Data for Epimicrobiomics Thinkering

Brent Pottenger is not only hawwt, lean, muscular, sexxxy and smart... so is his poo.

Characteristics of excellent health and excellent poo:
(a) Pancreatic Enzyme Digestion:  Elastase 1, marker for pancreatic enzymes (greater than 300 = decent; greater than 500 or immeasurable = PALEO AWESOMENESS).  No deficiency of pancreatic enzymes, fat malabsorption, undigested plant fibers, undigested fats
(b) No microbial overgrowths detected. Stunning gradient of Bacteroides/Prevotella. Exceptionally robust Prevotella populations detected
(c) No yeast overgrowths detected
(d) No parasites, worms, flukes, protozoa or pathogenic overgrowths detected
(e) No gut inflammation, anti-gliadin sIgA (current gluten reactions) detected
(f) No excessive or missing SCFA (products of microbial fermentation -- both good and bad flora)
(g) Excellent adiposity ratio of Firmicutes:Bacteroidetes (leanness) and correlates with Mr.Pottenger's BF (~~ 7-9% I estimate).

Digestion, Fermentation 101

Here's a primer on the gastrointestinal tract, digestion and fore/hindgut fermentation in humans.   I co-lectured with Tim Gerstmar ND at the inaugural Ancestral Health Symposium in 2011 at UCLA.
Ironically, I was ill at AHS and suffering from chronic fatigue (CFS).  Leanness was difficult to achieve, brain fog massive, and immune tolerances extreme (gluten, dairy, fiber, FODMAPS). It had all started immediately after a titanium dental implant, lasting from 2010 until summer of 2012 when I had it removed.  Nothing worked (yes, I tried everything). Finally, last summer, all the titanium, mercury amalgams, and gold crowns were extracted, and almost within 10 minutes I lost 5 lbs of peripheral edema and gained clear headedness.  Gradually signs and symptoms of metal toxicity, adrenal dysregulation and gut dysbiosis mostly disappeared.  A few months ago, I started dreaming again. Off/on I've been lucky to have leanness but it wouldn't last long.  Gluten actually was no big issue for me after Paleo, but dairy/nut intolerances became very problematic causing ankle swelling, mild joint achiness, and bloating.

Follow up is based on the latest labs below and Dx: bacterial/amoeba overgrowth. Starting to feel already even better and digestion improved.  Here are snapshots of AFTER v. BEFORE treatment.

(a) Pancreatic Enzymes (SIBO)
In 2011, my gut was not digesting. Enzymes were not produced at either the brush border (microvilli/small intestine) or apparently secreted in adequate amounts by the pancreas. Why? Gut stress, immune dysregulation from both microbial overgrowth and metal toxicity/suppression. With undigested carbs, fermentation occurs producing volative SCFA (small chain fatty acids) where it's not supposed: the small intestine. Undigested fats are delivered to the large intestine causing sometimes greasy, floating stools. I never had this, but the GI Fx test was positive. Undigested proteins (vegetable, meat) ferment into volatile SCFA, polyamines and stinky compounds (sulfur groups are stinky, like rotten eggs). Together, these further damage the small intestinal mucosal surface and induces SIBO (small intestine bowel overgrowth). Good protective flora are lost and both good and pathogenic flora overgrow, in the wrong place. Undigested fats and plant fibers make it intact to the feces. After treatment (surgery, Hg removal, diet, exercise, lifestyle, supps), this imbalance all reversed.  See AFTER, 2013. No red zones.

(b) Microbial Overgrowth (SIBO, Caecum/Appendix, Large Colon)

Overgrowth of 'good' flora occurred: Clostridias, Fusobacteria, E.coli.  A spike in SCFA propionate increased correspondingly.  I lost good species -- carb-eating Bacteroides, Prevotella, and huge populations of Lactobacillus and Bifidobacter. In his NYT article on the gut microbiota, Michael Pollan talks about how he lost his brawny Prevotella spike and developed a 'creepy E.coli bloom' after only one round of oral antibiotics, HERE.  He appears to eat a metric ton of fermented foods, so no doubt he has regained his Prevotella by now.  I'm so grateful that my gut did!  In fact the little tube became enriched by most of what seemed to be lost --Firmicutes, Bacteroides, Prevotella, Lactobacillus --- except some Bifido.  Prevotella is considered one of the best ecological microbiome metrics for neurotypical and healthy guts. In a recent study of autistic v. neurotypical children, it was found that the main 'core' genus missing was Prevotella by B Kang and James B Adams, PLoS, 2013.  In the enterotypes of neuroatypical autistic children, Prevotella was entirely absent.  The researchers also noted that a gradient of both abundant Bacteroides and Prevotella appeared optimal. Prevotella is also one of the top 3 genera observed to line our GI tract from mouth to anus. Its primary role in the large intestines is digestion of human-indigestible plant polysaccharides from cellulose, xylan, glycan, resistant starch, pectin, plants, shoots/roots/tubers, fruits, legumes/lentils, seeds/nuts, and whole grains.   Children in Burkino Faso have the most stellar Prevotella spikes (53% of total B + F) on earth -- they eat little meat (or gluten grains) but obtain protein from both (1) consumption of termites and (2) I hypothesize... microbiota-N2-fixation (amino acid byproducts from air (N2) + cellulose fermentation... ??incl carnitine, etc) from Prevotella, Bacteroidetes and N2-fixing symbionts from the termite gut microbiota.

For more info, read Dr. Leo Galland: Intestinal Permeability, aka Leaky Gut.  Once gut imbalance occurs, SIBO can take over and wreak havoc. Recall the gut epithelial layer tis one single cell layer thick. Undigested food and enteric bacteria, yeasts and parasites can quickly breach a damaged gut-barrier and proceed straight into blood circulation.  They can translocate to other organs and induce food allergies (soy, corn, nuts, eggs, citrus, dairy, wheat, oats, etc).  When the immune system tries to eradicate these perceived invaders with antibodies, then auto-immune diseases unfold. Muscles/joints, body fat and organs start to dysfunction when the immune-complexes (antigen+antibody) junk up joints, receptors, tissues and blood/lymph vessels.

(c) Yeast/Fungi Overgrowth (SIBO, Caecum/Appendix, Large Colon)
Normal is 'zero' yeast. Except for Mr. Pottenger's, I've never seen a report where yeast is less than 2. NEVER.  (I've never seen parasite-free/overgrowth-free result either.)  I run the GI Fx on nearly every client. Everyone shows fungal overgrowth and  it's indicative of dysbiosis.  Yeast is opportunistic and quite literally a bugger.  For over one year, I was on oral fluconazole 1-2x/month (I h**te pharmaceuticals especially liver-damaging ones). Nothing else controlled the yeast and in fact I had to dose escalate for only marginal control. When I returned to the U.S. my sister introduced me to Natren, and with immense gratitude, it worked in 24hrs (despite titanium/mercury).  Later, Natren, Prescript Assist, FloraMend and FloraBalance all helped to restore balance and minimize out-of-control fungi and allowed me to 100% discontinue Rx fluconazole.

(d) Parasites Are Not Paleo (generally speaking)

Overgrowth of pathogens, parasites and worms do not cause problems for everyone when the gut is anti-fragile, robust and resilient.  In fact, these stressors can even improve gut health and stability by stimulating the immune system.

However for the great majority of individuals sadly this isn't the case in my clinical experience. Perhaps, people's toxome is too excessive. When parasites or pathogenic overgrowth are found in the context of dysbiosis symptoms, IMHO it is best to treat.  Test, not guess... Or treat empirically like you would treat a dog/cat/pet. There are many sources of parasites in the USA and third world countries (like China).  They are overlooked, underdiagnosed, and ultra prevalent. The CDC reports more than 60 million men, women and children carry the Toxoplasmo gondii parasite. Salads, fresh fruit and vegetables, pet dogs, pet cats, tap water, cash $$, electronics, work computers, open bodies of water, licking doorknobs, camping, etc. are all common sources of parasites.  Read Dr. Leo Galland: Parasites.

D*mn, can't get lean. Though I gradually appeared to regain health and hormones, I couldn't achieve leanness. Somewhere between 2010 and now, I picked up an amoeba growth (Endolimax nana, see above) and opportunistic bacteria Morganella morganii.  Both are relatively easy to treat with 2-3 rounds of combination botanicals which have anti-microbial/anti-parasitic/anti-candidal spectrums (berberine, wormwood/artemisinin, oregano oil, curcumin, black walnut, herbs/garlic/ginger/biopiperine, etc). Sometimes these overgrowths can be benign. I have no symptoms except inability to achieve desired leanness and mild (but annoying) residual food intolerances.  Being compromised by metal toxicity, CFS and adrenal exhaustion may also have been factors for the inability to 'crowd' out overgrowth. In countries, like South America, anti-parasitics are sold over-the-counter. Several excellent botanical formulations are at iherb, my favorite international farmacy: Para-Shield, Thorne Berberine-500, Curcumin +BiopiperineTricyline, Paradex, Scram, Vermi-Purge, Paracid Forte, etc. I've used Metagenics Parex before, but it appears no longer made in the US. Metagenics Candibactin-BR is also excellent but no longer at iherb.

(f) Gut Inflammation, Anti-Gliadin sIgA
Gut inflammation all normalized after treatment. I had been gluten-free for months prior to the initial GI Fx test but we had gone to France and Germany for Thanksgiving six months earlier and ate hordes-of-irresistible-gluten (e.g.buttery croissants). The positive anti-gliadin sIgA shows that the immune system was apparently still reacting. Depending on the person, antibodies may require 6-24 months or longer to clear.

(f) Volatile SCFA (products of microbial fermentation)
With gut dysbiosis, butyrate and SCFA were all disrupted and low.  Propionate spiked -- likely due to excessive fermentation in the small intestines by overgrowth of supposedly 'good' gut flora (Clostridias, Fuso and E coli).  After treatment, this trend flipped.  Butyrate and total SCFA were all up to upper-normal ranges. This indeed matches my overall health -- less food intolerances, better digestion, far less bloating/distention, improved sleep, resumption of REM/brain-dreaming, adrenal tolerance, good adrenal hormones, great gonadal hormones, regained ability to do endurance training.

(g) Adiposity Profile: Firmicutes to Bacteroidetes ratio
Too much of either Firmicutes or Bacteroidetes is not ideal. Both help in extracting energy from chemical bonds in food. SCFA are metabolites of Firmicutes and Bacteroidetes fermentation in the caecum/appendix and large intestine. Partly the way they work is that the SCFA end products bind to G-proteins (GPR41) to control inflammation, brain-gut-gonad axis (cortisol/heart rate/etc), immunity and fatness. Just as omega-3 EPA + DHA increase lean muscle, reduce body fat and improve insulin sensitivity and inflammation, SCFA appear to do the same. Approx 55/45 to 60/40 may appear ideal.

Urine Organic Acids, Oxidative Stress, Toxin Evaluation:  2013

The urine organic acids (ONE=optimal nutrition eval) confirms that the gut dysbiosis was not severe.  No yeast dysbiosis was detected outside of normal range (very happy about the lack of brain fog/aldehydes/mycotoxins, too). In fact, vitamins, minerals, adrenal function, mitochondrial energy production and fat burning were all decent or exceptional.  It did point out that I'm a little low on detox nutrients -- vitamin A, all the B vitamins (being COMT (+/-) heterozygous), tocopherols, glycine, glutamine, magnesium and zinc.

The O.N.E. shows toxins -- alpha-ketophenylacetic acid (from my #*$&@ iPhone cover, styrene, synthetic rubber, resins, polyesters (sports bras, workout outfits), plastics, Saran wrap) and a-hydroxyisobutyric acid (from MTBE, gasoline additive meant to help gas burn 'clean' now major contaminant in California drinking water despite banning in 2003). Apparently mod-high levels of both are being excreted in the urine (after having spent 2mon in Cali 'detoxing' LOL aha). These are endocrine disruptors and damage DNA.

My kids and I have the GSTT1 deletion (glutathione S-transferase T1), and do not detox many xenobiotics well. Studies are finding oxidative, DNA damaging, and hormonal effects with even low exposures of polyaromatic hydrocarbons, pollution, benzene, acrylonitrile (gloves, plastics)styrene, gasoline, mercury (thimerisol sensitization -- eye drops, vaccines), mercury (low birthweight babies), mercury (compromised urine detox-elimination), mercury in medical students (increased mercury body burden), and countless other chemicals/metals in GSTT1 null individuals.  This genotype is even linked to whacked gender ratios of their offspring when chemically exposed... Dr. Mark Hyman MD reports he has the GSTM1 deletion and its effects, here.

SIBO Treatment, Healing the Gut-Brain-HPAT-Gonad Axis, and Followup

How did this SIBO &!amp;#$@ mess get fixed? Functional medicine labs, diagnostics, and treatment provided all the tools that were needed to finally reclaim my prior health, leanness, and brain-gut-gonad axis.  I am thankful for the opportunities to interact with several practitioners, my brilliant sister 'M', functional medicine doctors, and WAPF leaders over the last few years -- some very briefly -- they gave me the insight that I needed.

The root cause and antecedent event was the titanium implant which appeared to trigger some immune compromised reaction. There are implant failures (not me -- purrrfect, excellent ossification) but not many test Ig-positive on traditional or functional testing (MELISA, Clifford) at this time. Clifford CCR testing showed reactions to all mercury amalgam and nickel, but nothing for gold or titanium. After it and all metal were removed, the typical integrative medicine strategies all worked -- probiotics, raw fermented vegetables, exercise (earlier too fatigued to do any workouts), naps, yoga, laughter/friends, spiritual support, digestive enzymes, omega-3, mag/zinc/minerals, adrenal adaptogens, adrenal protocols (carb+protein+fat, every 4 hrs, sea salt 1/4 tsp daily), pycnogenol, gut support (marshmallow, slippery elm), betonite clay, charcoal, ghee, organic lard, rainbow vegetables, pastured pork and egg yolks, frequent bone broths, etc.  For followup, I hope the next phase will yield further insights.


Share and show me your GI Fx tests or integrative medicine lab testing results... I'd love to see it!