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)?
--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

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.


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.






Citations

Gravitz L. Nature. 2012 May 17;485(7398):S12-3.

Oregon State University (2013, September 16). Gut microbes closely linked to proper immune function, other health issuesScienceDaily

Greer RL, Morgun A, Shulzhenko N. J Allergy Clin Immunol. 2013 Aug;132(2):253-62.

Esteve E, Ricart W, Fernández-Real JM. Curr Opin Clin Nutr Metab Care. 2011 Sep;14(5):483-90.

Blad CC, Tang C, Offermanns S. Nat Rev Drug Discov. 2012 Aug;11(8):603-19.

Ivanov II,  Littman DR.  Cell. 2009 Oct 30;139(3):485-98.




DePalma A. "Mercury’s Harmful Reach Has Grown, Study Suggests,"  NY Times 1/23/2012.



Birdsong Differs between Mercury-Polluted and Reference SitesHallinger K, et al.  2010 The Auk 127(1):156-61. 
Shehata AA, Schrödl W, Aldin AA, Hafez HM, Krüger M.  Curr Microbiol. 2013 Apr;66(4):350-8

Aris A, Leblanc S. Reprod Toxicol. 2011 May;31(4):528-33. 

Sharma R, McAllister TA, et al. J Agric Food Chem. 2006 Mar 8;54(5):1699-709.

Bertheau Y, Martin P, et al. J Agric Food Chem. 2009 Jan 28;57(2):509-16.


Duggan PS, Chambers PA, Heritage J, Michael Forbes J. Br J Nutr. 2003 Feb;89(2):159-66.

Chowdhury EH, Nakajima Y, et al. J Anim Sci. 2003 Oct;81(10):2546-51.

Heritage J. Nat Biotechnol. 2004 Feb;22(2):170-2.

Jost T, Lacroix C, Braegger CP, Rochat F, Chassard C. Environ Microbiol. 2013 Aug 23. 

Fernández L, Rodríguez JM, et al.  Pharmacol Res. 2013 Mar;69(1):1-10.

Sultana R, McBain AJ, O'Neill CA. Appl Environ Microbiol. 2013 Aug;79(16):4887-94.

Bergmann KR,, De Plaen IG, et al. Am J Pathol. 2013 May;182(5):1595-606. 

Bethune MT, Khosla C. PLoS Pathog. 2008 Feb;4(2):e34. doi: 10.1371/journal.ppat.0040034. 

Chirdo FG, Rumbo M, Añón MC, Fossati CA. Scand J Gastroenterol. 1998 Nov;33(11):1186-92.

Qixiao Zhai, et al.  Appl Environ Microbiol. 2013 March; 79(5): 1508–1515.

Marc Monachese, Jeremy P. Burton, Gregor Reid. Appl Environ Microbiol. 2012 September; 78(18): 6397–6404. 

Zhang L, Li J, Zhou K. Bioresour Technol. 2010 Apr;101(7):2084-9.

21 comments:

Anonymous said...

I really enjoy your blog and especially your writing on the microbiome.

Is eating soil/dirt something you would recommend to improve gut flora?

Dr. B G said...

LOL -- of course. I was formula fed and received frequent antibiotics growing up. I think as a result I developed asthma (none of my younger siblings did) but I think what prevented other allergic types of conditions was the dirt I played in sometimes. I ran around all over the place until dark a lot on the east coast and liked to dig up ant hills for some add reason...

Can one find organic dirt? In the 70s one could, now, dunno....

Have you heard of Edible Earth by Magnetic Clay, company that produces Prescript Assist? I've taken that briefly (until I broke my jar)-- it's awesome!

Anonymous said...

Thank you for the reply!

You seem to have so much knowledge on the microbiota that I want to ask some more questions that I hope you take the time to answer:

- What do you think about resistant starch in regards to gut flora? You've probably seen the posts on freetheanimal.com

- In summary, what do you think is the best approach for someone looking to improve their gut flora? (No fecal transplant)

Keep up the excellent work!

Dr. B G said...

Hi,

I love your questions -- I wish I knew more but let's discuss what is known and make our observations from science, stories and history...

For RS (resistant starch), I think it definitely has a role for healthy gut function. Our good flora in the large colon need it to ferment into vitamins, amino acids, short chain fatty acids and oodles of other beneficial nutrients for us to absorb and utilize. Many of these we absolutely need for optimal health. Obviously I believe many things we are not currently measuring that the microbiota supply to us, for instance, immune function.

The people who cannot tolerate RS are those with SIBO. The inappropriate flora in the small intestines (which should be nearly sterile) will end up fermenting everything down the chute including RS, sugar and other disaccharides, FODMAPS, fiber, whole foods (meat, starches, etc). Some people know/feel it. Others with SIBO are pretty asymptomatic but they display the diseases of western civilization ....
--autoimmune diseases
--mood disorders, alcoholism
--heart disease, hypertension, strokes
--kidney, liver, gallbladder disease
--metabolic disorders, obesity, T2DM
--psoriasis, eczema, acne, rashes
--allergies, asthma, anaphylaxis to different foods or mold
--on and on and on

How to improve? There are great guides out there for SIBO and gut health. Healing starts when the bad things can be crowded and eliminated, then gradually the good flora can re-populate the gut and many things can rebuild (immunity, integrity of the small intestines/microvilli, damaged organds, cessation of autoimmune immune complexes and auto-antibodies).

One of the struggles I believe that people can have with the gut (because I HAD NEARLY ALL OF THEM SERIOUSLY NO JOKE)... is how difficult it is to actually pinpoint the root problem with gut health. for many it is actually toxins. I get frustrated...No one in paleoland acknowledges the lack of synchronicity with our polluted environment, the corrupt Big Medicine/Pharma and Big Dental industrial complexes, and our poor health... People do paleo (and/or RS) and still do not see their health goals attained -- lean mass gain, body fat loss, hormone balancing, adrenal dysregulation correction, etc. Certainly it is exponentially harder to heal now compared with only 15-20 yrs ago. Why? I've heard this from dozen of people and practitioners.

Dr. B G said...

(cont)
Yes -- I've read some of freetheanimal.com but I don't see deep and profound objective improvements. My metrics are different. I like to see hormones (serum or urine), Hgba1c, fasting and postprandial insulin (not just BG), and other longevity metrics... like increase in lean mass, reduction in BF% (body fat%), and improvements in adrenal and sex steroid hormones. Show me your free T.... Show me progesterone and estradiol for both men and women because these are truly j*cked and lead to sustained inflammation and other problems.

Obviously I like the Metametrix/GDX tests particularly the GI fx stool test and the first morning urine ONE (optimal nutri eval). Show me these metrics which also assess neurotransmitter metabolites, organic acids from dysbiosis, vitamins/minerals and metrics for environmental havoc (plastics, gasoline additives). These are the modern age metrics that need to be ultimately fixed to fix the gut, no? Gas and bloating help but many are just too oblivious to take note. Mental gaps, brain fog, and irritable, short moods generally escape as signs of intestinal dysbiosis yet these are the best, most clearest signs and symptoms.

To fix the gut, follow the functional medicine guidelines from Cleveland Clinic

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/preventive-medicine/integrative-medicine/

The 4R Model
Remove
One clinical paradigm used extensively in functional medicine is referred to as the 4R model. The first approach in the 4R model, remove, refers to the elimination of pathogenic organisms including fungi, pathogenic bacteria, parasites, and other ingested substances that include environmental toxins and foods. Food allergy is believed to be mediated by the passage of incompletely digested proteins across the intestinal epithelium, where it stimulates an immune response with the production of IgG antibodies. With continued ingestion of these proteins and translocation across the intestinal epithelium due to leaky gut, immune complexes are formed that result in immune activation. This is in contrast to the traditional concept of food allergy, which is IgE mediated and can represent a life-threatening, immediate type of immune reaction.

Infants have been shown to have impaired tight junctions of the enterocytes, and introduction of antigenic foods within the first 6 to 12 months is associated with the development of inflammatory skin conditions. Symptoms suggesting IgG-mediated food allergies include irritable bowel syndrome, apthous ulcers in the oral mucosa, serous otitis media, migraine headaches, asthma, chronic sinusitis, nasal congestion (without rhinorrhea), eczema, and memory loss. IgG-mediated food allergy might trigger other disorders (through stimulation of the immune system via immune complexes) such as rheumatoid arthritis and inflammatory bowel disorders. Peptides produced through the partial hydrolysis of gluten and casein that leak across an impaired GI mucosa have opioid properties and can result in neurobehavioral symptoms.

Leaky gut can be related to infections, use of NSAIDs, and the development of dysbiosis related to antibiotic use. One study has demonstrated a higher incidence of functional GI complaints in patients who had received antibiotics months before the development of symptoms. 22 Studies have also suggested that antibiotics can increase the risk of Crohn's disease. 23 Leaky gut can be tested for by ingesting lactulose and mannitol and measuring urinary ratios of these substances in the urine. Lactulose is not normally absorbed, and an elevated ratio might suggest impaired mucosal integrity.

Dr. B G said...

(cont)
Removal of offending foods by following an oligoantigenic diet and observing clinical improvement is the gold standard for assessing food allergies. Elimination diets are typically continued for approximately 1 month, and then food groups are reintroduced every 4 days or so. If symptoms recur with re-introduction (it can take a week of continued ingestion to develop clinical symptoms due to the delayed type of response from immune complex formation), then that food is identified as a possible trigger. Food allergy testing for IgG antibodies is also commercially available and can help guide decisions regarding dietary modifications. The results from these tests seem to be quite variable, so proceeding straight to the elimination diet is a better practice if possible.

Replace
Replace, the second approach in the 4R program, refers to the supplementation of digestive factors that may be reduced, therefore preventing optimal function. Hydrochloric acid production in the gastric mucosa is necessary for the optimal digestion of proteins and for the absorption of nutrients such as calcium. With increasing age, impairment in the production of HCl becomes more common. Osteoporosis has been described in patients taking proton pump inhibitors, which may be related to this mechanism. Pancreatic enzymes may be functionally deficient in a variety of clinical conditions including eczema and steatorrhea. The symptoms in patients with irritable bowel syndrome can improve with the addition of empirical supplemental pancreatic enzymes.

Reinoculate
Reinoculate is the third step. This refers to the supplementation of desirable microorganisms (probiotics) into the GI tract. This balance, involving hundreds of species of bacteria, can be impaired through the use of antibiotics and through exposure to environmental toxins. The environmental influence on the colonization of the intestinal microflora begins at the time of delivery and continues for the first 2 years of life. The maternal microflora inoculates the infant and influences the development of this symbiotic relation-ship and eventual milieu of the GI tract. Commonly prescribed probiotics include Lactobacillus and Bifidobacteria. Within each of these groups of bacteria, there are many species, and each has its unique characteristics and produces different effects in clinical trials.

Probiotics can inhibit pathogenic bacteria through a variety of proposed mechanisms that include competition for bacterial adhesion sites and bactericidal activity against pathogenic bacteria. Probiotics produce metabolites, such as butyric acid, that are beneficial to barrier function and colonocyte health. Studies have demonstrated the effectiveness of probiotics in children with viral diarrhea illness. Use of probiotics shortened the course of diarrhea and reduced hospitalization. 24 Probiotics have also been shown to modulate the course of ulcerative colitis 23 Saccharomyces boulardii, when given in conjunction with vancomycin, has been demonstrated to reduce the likelihood of recurrent Clostridium difficile enterocolitis. 25 Caution must be exercised in extremely ill patients because the use of this normally nonpathogenic organism has resulted in fungemia. The use of probiotics together (synbiotics) has been shown to be beneficial in specific clinical situations.

In addition to reinoculation, the addition of prebiotics can provide nutritional substrate for the beneficial bacteria that in turn results in the production of short-chain fatty acids (SCFAs), which are believed to provide up to 70% of the nutritional energy used by colonic cells. Examples of prebiotics include fructans, fructo-oligossaccharides, inulin, and arabinogalactans. Soluble fiber is also an important nutritive source for probiotics.

Dr. B G said...

(cont)

Repair
Repair is the final step in the 4R program. Nutrients that have been shown to support the repair process of the intestinal epithelium include glutamine, zinc, pantothenic acid, and essential fatty acids. Glutamine represents the major metabolic fuel for the epithelial cells in the small intestine. Pantothenic acid (vitamin B5) is needed for the production of coenzyme A (CoA) and acyl carrier proteins (ACP). CoA is a cofactor in more than 70 enzymatic pathways, and ACP is an essential cofactor for the fatty acid synthase complex. Essential fatty acids such as omega-3 from fish oils are involved in cell membrane function and also have anti-inflammatory properties.

Laboratory testing to support the clinician is commercially available. Stool testing for meat fibers can imply adequacy of HCl and pancreatic enzymes involved in protein digestion. Stool fat analysis can suggest adequacy of lipase production. SCFA levels can suggest the amount and composition of the beneficial bacteria. Stool cultures can assess quantitative measures of Lactobacillus and Bifidobacteria along with pathogenic bacteria and yeast. Stool should also be examined for ova and parasites. In patients with irritable bowel syndrome, empirical treatments with these supplements in a stepwise fashion can result in significant clinical improvements that might not have been evident based on laboratory results.

Dr. B G said...

Anon-- I talked about the antioligogenic diet under the migraine post. This is helpful for many. In the AHS talk, the elemental (liquid) diet is also super helpful but i find all of these may still be challenging one someone's adrenals are off-line or unplugged (dysregulated). The glucose/dextrose is challenging for BG control.

Cortisol -- cortisol causes ulcers and micro intestinal permeability so it can go without saying that those who cannot control cortisol have SIBO and intestinal permeability. Certainly I've struggled and I've fortunately discovered many many many 'reset' buttons that exist for cortisol and adrenal reprogramming (yoga yoga yoga massage qigong taichai; walking in green nature, embracing friends, oxytocin boosters, sex, herbal adaptogens, mag, zinc, B vitamins, extra omega-3, phosphatidylcholine, melatonin, stopping xfit (yeah sorry), stopping met cons (SORRY!), stopping ketosis and VLC, achieving circadian stability (day v night rhythms), etc).

Three things that helped my recovery the most are:

(1) Exercise (chronic cardio at low-mod intensity) -- this moves the gut along, prevents stalls in peristalsis which is common from decades of gut damage. There is scarring of the nerves which control peristalsis. The flora actually enjoy aeration and oxygenation I believe strongly. I think many paleo folks have misunderstood the value of cardio... I am NOT TALKING about enduro workouts for like Ironman 70.3 or other insane high intensity, high adrenaline extended torture. Just aerobics at talking conversational pace for a mininum one hour daily (or 10,000 steps).

(2) Fermented foods that are raw and unpasteurized at every meal. I did this for ~2mos before the GI fx stool testing and I think this made the biggest diff because I didn't do any of the diets, in fact, my kids and I kinda porked out returning to the USA (GFCF sorta). 'Kraut did all the 4Rs. It 'removes' by crowding out the nasties.

(3) Charcoal, edible earth, bentonite clay -- these bind up toxins for immediate elimination. REMOVE the sh*t that happens. We are animals and we get parasites or pathogenic overgrowths. Have you watched Planet Earth? Did it not shock you how often the animals are seen traveling, foraging and eating clay from water holes? Some evade dangerous predators or tread past high precipices to obtain a certain type of clay. Why do animals do such crazy things? Because parasites are not paleo. They need to be extracted pro-actively when problematic. Certain clays also provide salt and rare minerals missing from diet or depleted from stress/poor diet. That is us too... we are depleted of zinc, magnesium and many of the B vitamins. Why? I have no idea. My kids and I supp all of these very routinely and have a pristine diet, yet we scored helluv low (yellow zones, rare red zones) on the Optimal Nutri-Eval. Surprise to me. I can tell enpirically as well (blotchy skin, acne, hormone results etc) but it is nice to have the objective data. Where do the stressors come from? The gut. Parasites and the pathogenic overgrowths (fungal, opportunistic, etc)

Thoughts? What have you tried? How do you objectively evaluate? Is this spam?

Dr. B G said...

Here's a paleo version of GAPS

http://www.eat-real-food-paleodietitian.com/support-files/SIBO-gut-healing-protocol.pdf


Resistant starch (rice, potatoes, etc) are added in the 3rd/final stage after initial healing.

The RD did a fantastic job and I like the chart summary. Check it out

Anonymous said...

Thanks for the really thorough answer!!:)

I came by this blog by accident, and it's definitely a new favorite (Dr. Art Ayers at Cooling Inflammation isnæt posting more either so I need some new reading material on the microbiome)

I've got some raw potato starch (resistant starch) and I'm also considering regularly eating some dirt, hence my questions.

I've already incorporated probiotics, prebiotics and fermented foods in my diet, but my GI tract is still not in optimal condition...


Dr. B G said...

Hey Anon,

Very glad that you enjoy the topic! Tell me what you would like to hear more about. Future topics are
--fossilized feces
--ancient mummy microbiota
--how we are not vegans per our microbiota
--mental health and the microbiota
--how toxins affect all the above


I love Art Ayers -- we had some deep convo a few years ago. I concur that cooling inflammation is certainly key in all Western ciz diseases. I hope you find the source of the fire! Follow the flames.

Hyman one of the vocal leaders (and very pretty) of functional medicine always says that the problem with conventional medicine is that they take the battery out of the fire detector while the house continues to burn down....

Let me offer you the tools to evaluate your suboptimal gut. You will help me as well as I would love to see more health recovery via healing our microbiota which is the immune system. Have you heard of the American Gut Program? The first results just came out...
http://americangut.org/wordpress/wp-content/uploads/2013/09/module1_Sept_16_small.pdf


However it is very non-descript and uninformative compared to the Metametrix/GDX comprehensive GI function stool PCR analysis of the 16S rRNA of our microbiota, digestive capacity, identification of pathogenic overgrowth and parasites.

Would you like to do one and also assess the organic acids on urine?

With insurance (exluding HMO ones) GDX offers theses labs for a really excellent price, starting about one year ago. In the program EasyPay deposit the cost is as below and I will charge a half-off discounted consult fee ($50):
Optimal nutri eval (ONE) $129
GI fx stool analysis $99

Let me know. I can drop ship by FedEx ground in 3-7 business days.

I like BG blood glucose measurements (of course I AM DRBG) but it is an incomplete metric to follow health. Find the source of the smoke and flames. Utilize advanced metrics.

RE: dirt. I love dirt but dirt is like real estate. Optimum is a factor of: Location LOCATION LOCATATION! The dirt that has been shown most helpful imho to humans is compost and dirt at the roots of our edible plants... there is a symbiotic relationship between the microbial nitrogen fixers that reside at the roots of the plant and that particular plant, which extends to us -- the ultimate 'consumer'. We actually may benefit abundantly as our immunity thrives upon ingestion of these microbes that live on and near plants in the soil. They in turn harvest our gut products (sialic acid, fucose, tasty glycans, etc) and the byproducts of other microbes and complete another symbiotic ecosystem in our gut environment.... Anyway I think you should consider prudent collection of dirt!

grace

Anonymous said...

Excellent!

I would like to see posts on all the topics you mention, and also I would really like to see a post where you summarize the important things to do for å healthy biome...

I would like to do a metametrix test, but the thing is that I live in Europe which makes these things extremely expensive to ship through FedEx, as I experienced with American Gut (around $150 to send the package)

Thanks again

Dr. B G said...

Hello,

Great -- I'm getting busy soon (my hibernation in the burb home is nearly over) so these are all percolating and hopefully can publish before getting overwhelmed.

Did you do the American Gut????! Please share how it went! What did you think of the first report? Are they completely clueless?? Have you read Jeff Leach's take (well of course you must have)...? I love LEACH ;) I don't know how exactly he calculated the Prevotella spikes -- his is robust. If you look at Brent Pottenger's, it is also equally robust IMHO and his diet is nearly carnivorous with fremented high fat Greek yogurt + coffee. Thoughts?

I'd love to see the changes in your microbiota with the change in quality of low GI carbs, fiber and gut healing biohacking... it's a bummer you are limited by the shipping costs. Can you contact some academic institutions in Europe who would love to microarray ur poo? Want me ask around for you?

Yes -- expensive for me to ship FedEx from China USD$50-100 so slightly less. Actually bodily fluids including stools are illegal so we have to go thru approved channels which are costly due to admin fees... I won't be able to repeat the testing until we return to the States, Australia, UK or EU.

g

Anonymous said...

I haven't gotten the results from the American gut project yet, and I'm unsure whether they even received my sample since I ended up sending it through regular mail since FedEx was so expensive.

I like Jeff Leach and his writing on the human microbiome, but I think he focuses too much on fermentable fibers (if that's possible;)) and he never mentions those people with severe gut flora damage, and only seems to focus on soluble fiber, dirty veggies etc. which might be enough for regular people with some mild damage to the gut microbiota, but not for all those people with moderate-severe IBS, skin problems and more.

Dr. B G said...

Thats because Leach is 'healthy'... he must not have pathogenic overgrowth and parasites during the project, and at least I hope it would be revealed. I wonder if they had pre-paleo microbiome versus his post-paleo Am Gut one??? That would be extremely revealing.

Ayers does look at diseased guts but I find his understanding is limited as well. In functional medicine, EVERYTHING is the gut -- the alpha and omega...

Anonymous said...

I'd like to see you dig into the role of plant pollen in the ancient diet. Plant pollen seems to escape digestion in the small intestine much like resistant starch and other fermentable fibers.

Coprolite studies show high levels of plant pollen--indicating it was eaten in large quantities--not just there by accident. Specifically, cattail pollen seems to have been a prized food.

Dr. B G said...

Have you eaten pollen? It's delicious tasting of flowers, nectar and honey -- Berkeley Bowl and many health food stores sell pollen in the refridgerated region. I don't know where or what plant honestly my pollen came from but the granules were about large sea salt size.

Eating pollen is purported to lower allergies. No doubt there are immune benefits and no doubt ancient hominids learned to harvest them, just like early small grain grasses (SGG). The question really is what didn't and don't hominids eat...??! Certainly it is the case now -- adulterated GMO and transgenic food is about 70-90% of most industrial nations' food pyramids -- wheat, soy, corn/HFCS, canola oil, sugar.

Did you see this post on neanderthal extinction?

http://drbganimalpharm.blogspot.jp/2010/07/middle-to-late-paleolithic-neanderthals.html

majkinetor said...

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%??)
I keep seing this repeated without any reference. It looks like this view is mistaken. I was recently reading a paper about this related to HIV infection and authors reanalyzed the data not only on humans but on various animals. They found that only 5-20% of immune system is in the gut [1].

Our good flora in the large colon need it to ferment into vitamins, amino acids, short chain fatty acids and oodles of other beneficial nutrients for us to absorb and utilize.
Its question how much of these we can utilize. Most animals practice coprophagy in order to obtain nutrients from feeces.[2] When you prevent that behavior, you get nutritional deficiencies: "Experimentation has revealed that the rat that does not have direct access to its feces on extrusion from the anus requires a dietary source of thiamin, biotin, pantothenic acid, folic acid, vitamin B-12 and vitamin K". Prevention of coprophagy not only helps nutritional deficiencies develop more quickly but may also cause quantitative dietary increases for nutrients. . This is true also for ruminating animals (to lazy to find citation from my library). Similarly, human faeces contain B12-like produced by microbiota in the colon, but this can't be used. It looks like that small amounts of vitamins are produced by microbiota residing in small intestines. This also questions the importance of this part of the gut and perceived near sterility that you mention which is actually a gradient of microbiota starting from the cecum and moving toward small intestine[5]

Ofcourse, to get most of your microbiota first you need to keep the zoo like a pro which means that you need to know the kinds and amounts of your carbs [4]. Since gut microbiota changes depending on your behavior, its not entirely clear could you rely on it for micronutrient production, especially if you account the fact about nutrient stealing. Its probbaly enough to prevent deficiencies tho, even for vitamin C (which could explain why some people/g.pigs never get scurvy).




[1] "Do most lymphocytes in humans really reside in the gut?" http://goo.gl/ditpp3
[2] "Effect of coprophagy on nutrition" http://goo.gl/aoFxVF
[3] Coprophagy and related strategies for digesta utilization http://goo.gl/CIptIS
[4] INTESTINAL BACTERIALSYNTHESIS AS A SOURCE OF B VITAMINS FOR THE RAT http://goo.gl/WvaG14
[5] Vitamin B12 synthesis by human small intestinal bacteria http://goo.gl/XSI2mW

Dr. B G said...

Maj,

You know i love u and miss u? Yes -- I couldn't recall the THIRD REASON why I abhor rat studies.. But it's because they eat their own poo. You stated it boy.

Let me ck out the links. I found only ONE study from the 1940s or 50s where a gastro MD discussed how 70-80% was arrived at. Let me dig out... Yes it needs confirmation or at least revision by what is now know about the microbiota

Thank u
G

Bono said...

Really a nice and informative blog drBG! Really impressed!

Although sometimes I have to put my brain to extrawork :)and recall my scientific skills :).

I need an opinion regarding a health issue: multiple infections in the gut, CFS, SIBO, h.pylory...im Eastern Europe based.

I've managed to reach now a balance after 4 years of struggling and "unknown" ilness. But no matter what progress I've made stuck with a stubborn worms infection which didnt want to clear out despite of classical drug treatment. Any idea what could impaire that?I was thinking about resistant species but ..

Couldnt make a real progress because of that...with SIBO and candida. Rounds of Ciprofloxacin made it worst. Have also CBS/SUOX defect (of course candia and chronic Hpilory hipotyroid and cortisol prb).

Would love to hear an opinion of yours. I know is not a medical advice or something.

Many thanks
Bono

T.M. said...

Just discovered this wonderful and informed blog--thank you Dr.BG. I have also speculated on the potential for an "enteric-mammary" pathway based on my experience as a mother.

A little background...I have pretty good health comparatively but have suffered over my life with eating/sleeping issues, inability to gain weight and acne. I was born vaginally and breastfed for 6 months. Had a severe case of food poisoning without medical treatment under the age of 1. Apparently after that I lost all my baby chub, became a very fussy eater, couldn't take milk or eggs, and was always irritable and underweight. Developed lifelong face/chest acne at age 11, chronic sleeping issues related to melatonin and cortisol, and 14 years of birth control pills. Thankfully not much antibiotic history.

My Mother was not breast fed, was chronically sick, had HepA, tonsils removed, irritable bowel/excessive putrid flatulence, agressive dental caries,a 35 year long chronic sinusitis, and now MGUS--literature points to chronic low-grade infection.

This all despite me growing up with an organic garden, non-processed non-typical Western food diet, backyard chickens, and fermented raw milk. So now this picture makes a lot of sense with the evolving knowledge of the microbiome. What bacteria are we missing or dysbiosis do we have??

Fast forward to now and my child was born vaginally and I didn't even wash him for a week! Exclusively breastfed but very irritable/colicky (similar to me), and by 5 months he starts developing excema patches all over body. Doctors were useless. I cut out all gluten and dairy from my diet and his excema goes away. Discover if I challenge with any dairy in my diet he gets excema patch within 24 hours. So my hypothesis is that a dairy protein was either crossing through my leaky gut or the hypothesized enteric-mammary pathway resulting in its presence within my milk. I gave him infant probiotics and eventually in his second year he stopped reacting to my dairy challenges but would still react if he himself tried yogurt. He didn't outgrow his "dairy protein intolerance" until age 3--or rather developed a mature gut. He was breastfed until age 3.5 and is now 8.

Did my leaky gut heal? Maybe. I still probably had SIBO, unbeknownst at the time. Doctors still useless and patronizing in my attempts to find an etiology for my symptoms. Speculations of hormones, thyroid, adrenals, etc., but I finally made a connection with inflammation and gut through self-testing and tracking patterns. I didn't do the 4R's in order as I wasn't aware of the protocol. But 18 months ago I went dairy-free for 4 months, took 50 billion probiotics and tried adding inulin. Curiously both my Mother and I cannot tolerate inulin due to the significant bloating/gas factor plus stench. The probiotics only gave me non-smelly gas that took a few weeks to settle. I now make kombucha and kimchee, and have begun a protocol of Saccaromyces boulardii, L-Glutamine, and Curcumin. Discovered that I absolutely cannot tolerate corn--I'll get constipated, stinky farts and breakouts, but have no reaction to wheat gluten. Luckily I'm married to a Jamaican so plantains, rice & peas, and coconut milk are regular food. But now I'm going to experiment with RS. Based on my other reactions I expect I have SIBO and will get some degree of gas, just hope it's not the stinky type! All said...my acne has been in remission for the first time in my 39 years and I've put on some healthy weight so something is going right!

Much thanks.