Sunday, June 1, 2014

What are you missing? What's your gut missing? Show me the antibiotics you've been on, I'll show you your ABSENT ALLIES

(1) Prakash et al, 2011
The Gut Microbiota and Human Health etc
Here's your gut (see 3 diagrams) and a couple of factors that make you who you are:
  • digestive capacity: 
    • AMY1 (amylase in saliva)
    • gastric pH
    • pancreatic enzymes (elastase)
    • gallbladder function
    • bile
  • your microbial allies (see above diagram): 
    • mutualist aerobes (upper GIT) 
    • mutualist anaerobes (lower GIT)
  • colon fermentive capacity: 
  • colon interior and epithelium association: 
    • surface and mucus layer (Clostridium, Lactobacillus, Enterococcus)
    • lumen (the rest)

(2) Sekirov et al, 2010
Gut Microbiota and Human Health

Absent Allies: Imbalance Leads to Health Havoc

Have you lost your friends?

When vital parts and precious pieces are missing, the gut has a difficult time doing what it's supposed to do -- protect you from infections and pathogens,keeping serotonin and melatonin in circulation,  recycling cholesterol, and energizing the brain and muscles. In ancient times, the average human likely had an enormous load of microbes from daily exposures compared to modern lifestyles. Think about it? No cold storage -- everything fermented and room temperature. No toilet paper. No C-sections (yes sadly both more moms and babies died). No pesticides or antibiotics which indiscriminately wipe out too many protective microbes. The modern gut is reeling from the deficit of these allies which touch and provide feedback to nearly every immunological, neurological and hormone pathway.

So let's say you a had a couple courses of the pink syrup growing up (Amoxicillin) then 1-2 courses of Cipro for sinus or upper respiratory infections as an adult. Not much but what does the resultant gut microbiota look like? The infertile mom? The constipated babysitter? The morbidly obese CEO? The lymphoma patient? The athletic Ironman with alcohol-dependent ADHD? The pale boy who shot up the high school? 
Petersen, Round, 2014
(Amoxicillin, Cipro and Vancomycin v. Alterations to Microbiota Ecosystem)
Defining dysbiosis and its influence on host immunity and disease
Amoxicillin will knock out beneficial Lactobacillus, Bifidobacteria, Enterococcus and Enterobacteria which may lead to overgrowths of opportunists and yeasts if the the microbiome fails to remain resilient, robust and able to recover. 

The Cipro may then annihilate to extinction anything else that Amox failed to exterminate: the ginormous Clostridiales group and the major player Faecalibacteria (aka F. prausnitzii). 

Decimating or disorienting F. prausnitzii isn't a great idea. It works in parallel with Bacteroides to build up the thick epithelial-guarding mucus layer. It's like stripping off your SKIN or scalping your gonads. Very very bad idea. F. prausnitzii is so big it is the largest, single species that composes a healthy gut: 3-6% of all fecal species.

For example in IBD (ulcerative colitis and Crohn's), a huge chunk of Clostridiales is absent whether the diseases were in remission or acute stages. Past antibiotics may or may not have played a role per studies. Where did the Clostridiales go? Were they ever transferred at birth or did mom lack them all secondary to antibiotics, lack of healthy soil exposures, stress, sugar or a high refined carb SAD?

Bacteroides and Clostridiales are typically 1:1 in balance roughly speaking. By thrashing the Clostridiales leaves the more opportunistic and hearty Bacteroides to override symmetrical ecosystem stability. In ulcerative colitis and Crohn's, what ends up occurring is Bacteroides breaching the mucus and directly attacking crypts, colonocytes and adhering like colonies of pathogenic vipers. They set up shop and don't leave (look at ugy pictures). Re-establishment of an encompassing mucus layer is as important as getting Clostridiales back in the hood and re-creating parity.

Both Bacteroides and most of Clostridiales love to ultra-fast ferment resistant starches. Feeding a sick ecosystem is probably not as critical as first bringing order by returning absent allies back to prominence. Butyrate improves mucus linings but only if bifidobacteria and other commensals are properly located.

Norm Robillard talks about the start of his health odyssey and GERD on this podcast: Paleo Mag Radio (Tony Federico) episode 38, Resistant Starch Take 2. GERD is a form of dysbiosis and broken balance in the gut with microbes lingering up in the small intestines where they do not belong. Norm has conducted research on Cipro.

Knocking out Clostridiales is one step away from inducing iatrogenic C. difficile colitis (unremitting diarrhea, weight loss, dysfunction, death), a condition which kills 14,000 people annually but affects millions. IMHO the vancomycin treatment is almost as bad as the disorder itself in terms of gut and overall health.

  Clostridiaceae --  massively feeds butyrate/SCFA to colonocytes and immune cells
  Eubacteriaceae -- a big RS eater
  Ruminococcaceae -- contains the keystone RS degrader

(3) Marchesi, 2011
Human Distal Gut Microbiome

Microbiome Misinterpretations?

So you can see 3 views on the microbes in our gut. Unless you do functional medicine lab testing (GDX, Biohealth, Doctor's Data), all miss the same things: yeasts, parasites, pathogens, and helminth worms. All 3 views show slightly different commensals and mutualists based on slightly different testing methodologies and diverse healthy control subjects that they tested. Actually, I like them all because you can see the variance and diversity and this reflects our ancestry and genetic evolution. What is clear is that research has finally shifted to testing non-healthy subjects and the evidence reveals vast absences in different diseases. Essentially in nearly any disease, researchers find missing mutualists and commensals -- all the above.

Vast extinctions. Empty tropical rainforests. Barren tundras.

Now you are starting be aware of what is gone. What does one have to do to find and recover stolen gems and diamonds? One can't redo birth and squeeze down lactobacilli-coated slides or start licking porcelain bowls which harbor worms or parasites.


Kor said...

POOOOP transplants! <3

Anonymous said...

Maybe I just have a sick mind, but one surely can do both...

Unknown said...

Hi Grace -

Love the blog, your work.

Am I correct in saying that you believe high levels of Clostridia spp. is always a positive? I just received by 2200 results back {entire report below} and my Clostridia was 5.9, while my Lactobacillus is very low vs. the Bifido. My advisor felt these needed to be brought back in balance and suggested stopping any Bifido and adding Lacto species along with Mutaflor. {currently on Prescript Assist and RS}..However, from what you are posting and the Bulletproof interview with Richard and Tim, the belief is that Lacto could indeed be "Fat People" bacteria. Thanks! Mike :)

2200 GDX Report
Obligate Anaerobes
Bacteroides spp. 3.0
Clostridia spp. 5.9
Prevotella spp. 2.0
Fusobacteria spp. 2.2
Streptomyces spp. 1.9
Mycoplasma spp. 2.9

Facultative Anaerobes
Lactobacillus spp. 2.0
Bifidobacter spp. 5.3
Escherichia coli (E. coli) 1.6 L

Yeast/Fungi +3 => 10000 pg DNA/g specimen Expected Value: Negative

Parasitology EIA Tests:
All In Range > All Negative

Adiposity Index
Firmicutes 68%
Bacteroidetes 32%

Beneficial SCFA
Total SCFA: 54%
n-Butyrate: 15.7%
Acetate: 48%
n-Butyrate: 48%
Propionate: 20%
Valerate: 2.4%

Lactoferrin: 0.5
WBCs: Negative / Negative-Rare
Mucus: Negative / Negative

Fecal sIgA: 44

Additional Tests:
pH: 6.4
RBCs: Negative
Color: Brown

Elastase 1: >500
Triglycerides: 171 (high)
Putrefactive SCFA: 3.2
Vegatable Fibers: Rare

LCFAs: 17,4 (high)
Total Fat: 29.5 (high)
Cholesterol: 397 (high)

G said...


The plan sounds prudent. Do you have a lot going on? The elastase and malabsorption are significant to me as well. Do you think the pancreas inflamed?

Lacto can be opportunistic -- it is higher in obese when there is dysbiosis (sibo)! Which Lacto were you considering? Have you read Mr. Heisenbug's blog? L plantarum has many gut healing properties.

Have you heard of GCBC, good clostridia bad Clostridia? It's my book that I haven't published yet lol. You need some good Clostridia. If it was me I'd pound some AOR probiotic-3. E coli works co-op with Enterococcus which is AOR (formerly known as S. faecalis).

Anon~ Yes indeed. I would too in a different world.

Kor~ Go healthy manure and mud!

Unknown said...

Grace –
Thanks for your time and insight. Fat metabolism is definitely puzzling but I haven’t looked at the pancreas specifically (but certainly will now). In addition to the stool results, my recent WellnessFX testing yielded high free fatty acids (FFAs -0.81) – the culprit, high Omega 3s (11.5 index; EPA 2.7; DHA 8.8); In contrast, Omega 6 to 3 ratio and AA were both good.

My consultant has recommended Ox Bile (125mg) to aid in fat digestion and also as part of a mold detox {2200 score: +3 => 10000 pg DNA/g specimen with methylation pathway issues} which also includes a regimen of Physphastyidyl Chorline, Lipase, Interphase Plus and Biocidin. Not sure whether mold issue would tie into fat digestion? {Additional notes: low adrenal (4pt test); low T3 w/ high T-uptake; raised Monocytes, high MCV; Viral panel pending)

I’ve previously attempted the probiotic trio {PS, Primal Defense, AOR -3, } – Prescipt-Assist and Resistant Starch performs well; Primal Defense induces some malaise; AOR-3 is the virtual hammer, only to be trumped by MegaSpore. However, with the mold/yeast reading and/or lack of Lacto, possibly just die-off symptoms and I should press on?? Will definitely add L Plantarum 299v and report. Thanks again! Mike.

G said...


You won't get anywhere without decent adrenals (and lower fungal loads). Focus on adrenals if you're practitioner has not discussed yet. Sounds like an excellent course!

AOR, megaspore, L plantarum and many other probiotics are anti-fungal but they can only do so much with high fungal loads and resistant biofilms and low thyroid/adrenals. Body temps, gastric acidity, trypsin, etc are all vital parts of digestion that control yeasts and pathogens.

Thanks for your reply

David said...

Hi Grace,

As always, very informative. Good stuff!

Do you plan on writing a detailed posts on that other big player in the gut microbiome, yeast? I've had remission 3 times now from CFS with supplements that could affect yeast. Biotin, Super Thisilyn, and S. Boulardii. Only to relapse. I'd love to know how to pursue that.


aerobic1 said...

Interesting post, Grace. Having committed premeditated murder by way of (13) IV Lyme treatments via IPT that incorporated a cocktail Rocephin (Ceftriaxone), Tygacil (Tigecycline) and Doxycycline (similar to tetracycline), it was of little surprise the damage (decrease) I did to my beneficial flora and the increase in commensal flora.

When I looked at the susceptibilities of each of these antibiotics there was no beneficial strain that was not susceptible to this concoction. After many months of repopulating the gut, my latest Doctors Data Comprehensive Stool Analysis/Parasitology x 2 has improved with the exception of bifidobacterium which shows no growth (NG). I find that interesting. I have been using 50 billion CFU of Klaire Labs Ther-Biotic Complete probiotic ( daily along with fermented and cultured foods but still no bifidobacterium growth is evident. Perhaps it is time for a different approach?

I have no preconceived expectations that my microbiome will ever return to normal; whatever normal is. Through the eyes of Alessio Fasano, Jeroen Raes and others, return to a balanced flora is often difficult if not impossible to achieve.

Steve said...

Hi Grace,

I started AOR-3 in addition to PrimalD (which I've been on for several years). Also eating a fair amt of RS...all with the hopes of improving my crohn's. since starting the aor-3, my stools are much smaller, which is positive for me, but I have been passing a large amount of mucus. prior to the aor3 I was having several large stools daily. i've only been on 1 cap/day of the aor-3 for a month now and not sure if I should continue, reduce the dose, increase the dose? otherwise, I'm feeling good. not sure what to think of all this mucus? does anyone have any thoughts? thanks in advance!

BJ in TX said...

I had a serious psoriasis flare which threatened to take over my body about a year ago. I went to the doctor very reluctantly and specifically asked for an antibiotic to stop the spread. He prescribed minomycin which in a matter of days not only stopped the spread, but completely cleared my skin. I am now on the AIP pale diet which has helped tremendously with the psoriatic arthritis, but has not so far done too much for the actual psoriasis. What "bugs" would destroy the nasty bacteria that promotes psoriasis? Any speculation? I would appreciate any thoughts along these lines. Thanks for your time.

Unknown said...

Hi Grace,
Thank you for all the great work you do! Your insights are amazing and I know if I can keep up with you I may just be able to put my AI in remission.

I have hashi's and a very bad gut...have been severely constipated since youth. (sent my gi effects a few months ago) I also believe my adrenals are toast so your recent reply on those being critical to gut rehab is of great interest. I've been using the protocol with prescript assist, aor and primal defense, potato flour and psyllium, with little improvement. Wondering if you could provide some guidance on where to find a proper adrenal protocol...I'm tapped out on the D.O's and naturo's..lots of tests not a lot of results unfortunately.

Unknown said...

Hi Grace, One correction: You say "Norm Robillard talks about how Cipro may have contributed to the start of his health odyssey and GERD" If you give a second listen, I talk about Cipro, but just as an example of a lifesaving drug. I worked on the development of this antibiotic but did not take it. Cipro had nothing to do with my developing GERD.

Dr. B G said...

I hear ya. It's an epic battle for some (eg I still have relapses as well!)

Mercury loves misery, eg candida. We all have some mercury sadly.

I love your thoughts: bugs over drugs! Shoot for bifido and L plantarum and other anti-candida strategies (merc detox, herbals, SBOs, prebiotics), and topical magnesium (like magnetic clay magnesium baths -- pamper yourself and your skin! lol).

Feed well and water -- please look at step 2

Google dr lam or dr wilson for adrenal exhaustion. Hang in there. I hope you find respite and recovery rapidly soon.

I'm sorry -- I listened while on a loud Shanghai taxi ride. corrected now.

lisao said...

Don't give up so easily! It can take time and trying different probiotics. Maybe the Klaire labs ones just aren't so great for bifido. You could try natren. Or any number of others. I would just consider that your improvements mean you're headed in the right direction and that is great! It means change and improvement is possible. I wouldn't get all negative and low expectations just because everything was not better this time.