Friday, March 6, 2015

Peering into Four uBiome Stool Analyses (Part 1): Benefits of BIONIC FIBER; Emergence of Toxin-secreting Clostridium Botulinum and Loss of Over 1/3 of Gut Diversity and Species With 'Raw Bob's Red Mill Potato Starch'

Quantified Self Experimenter: R. Sprague

Recently Richard Sprague shared his data with me and asked me to review his uBiome analysis of his stool microbiome. He's a bona fide data collecter and fan of QS (quantified self). The other day he shared his oral microbiome results. Lot of wonderful things going on there in his mouth! For his gut on potato starch, not so much. We will compare this gut results to two other uBiome samples from individuals taking a Bionic Fiber combination (psyllium, acacia, inulin-FOS, etc) and a diet based around the 7 Steps for an optimal gut microbiota.

About Richard Sprague, 51 yr old QS-er, super healthy, lean (160 lbs, 6') and SUPER BRAINY:

"At the time of the three samples, I did not take any supplements or other medication of any kind. I drink one cafe latte per day, plus about 5 servings of alcohol (usually beer) over the course of a week. I am an omnivore, though I tend toward paleo-style eating (no processed food, plenty of fat+meat). I eat wheat- and other gluten-bearing food a couple times a week, along with dairy, and I don’t notice any difference at all whether I abstain or not."

Fiber intake (MyFitnessPal): 15-20 grams daily (below average; RDA for males 38 g/day, females 25 g/day if you subscribe to that)

Three uBiome gut results:
Sample taken on 5/16/2014 'Pre-RUMPS' (raw unmodified potato starch)
Sample taken on 6/6/2014   (on travel, camping, varied diet)
Sample taken on 10/17/2014  'Post-RUMPS' (raw unmodified potato starch 2-4 TBS)

Prior to the Oct 2014 uBiome he used 2-4 TBS 'raw potato starch' (RUMPS) sporadically for about 2 weeks to hack his sleep and stools. Both had some quantifiable changes: sleep increased from 6.27 hrs/night to 6.52 hrs/night and stools increased from 1x/day to 2-3x/day. Quality of stools may have worsened; he reports Bristol 4 or 5 (mostly 5) prior to RUMPS and 5 after RUMPS. Below I review May and Oct results. Our gut biome changes hour by hour depending on diet and lifestyles. There are many 'drivers' but what we stick in our mouths is the biggest driver. I decided to only compare these May and Oct results as 'best' gut representatives.




How Citizen Science Helps Us and Our Guts

I love ubiome -- it is not diagnostic but it is a valuable tool that tells us the terrain of the lower gut and a little bit about the upper gut (small intestines). It gives us the profile for all the bacterial colonies in the colon. With tools that Richard developed on his github, one can integrate the raw taxonomy and play with them in Excel. (AmGut data FYI is not so simple). uBiome also has fantastic turnaround times -- only 2-3 wks for results to come back. I just submitted mine this week, and looking forward to pouring over it soon. 

Fecal samples have limitations. They may or may not represent what is going on at the mucosa level. Sometimes vast changes are going on at the intestinal mucosal level but they don't spill over into the lumen and resultant fecal matter to truly tell us the representive microbial colonies going on there. Still I like poop. What we poop is what we are, just as what we eat is what we are. Diet is the biggest driver for shaping the gut microbiota. By just modifying diet and dietary supplements, we can perpetuate a better gut as well as better health.

Another limitation is that looking at bacteria alone doesn't give us the big picture for life in our guts; non-bacterial colonies such as yeasts/candida, parasites, helminths, and protozoa are also significant contributors to gut health and dysbiosis and they're not not analyzed. These are better seen with a urine OAT (organic acid test) for clostridial and yeast metabolites or a specific Genova or Biohealth 401B parasite analysis. 

The science is still in its infancy. uBiome and other institutions have not identified all the species. Depending on someone's gut composition, the unique # of species known and identified is about half to 70%. Therefore 'species norm count' will not add up to 100% (though 'phylum norm count' and 'order norm count' are typically close ~96-97%).



Sprague's Github Tools to Help You Analyze Your uBiome Stool Samples

Sprague has created a couple of tools to help you manipulate and play with your big data from uBiome after you get your results back. I find it helpful and excellent to see the phyla, order and species on the Excel sheets. Patterns emerge, changes can be tracked and a nice story happens.

https://github.com/richardsprague/uBiome

He has a 'Getting Started' short list of instructions and very easy to follow steps to take the 'raw taxonomy' from uBiome's dashboard and transform into different data files (JSON, EXCEL, TXT, etc). Read his 'Beginner's Guide' for great info!




Citizen Science Reveals Dramatic Loss of Diversity and 36% Extinction of Known Species

Let's talk about Sprague reported no change in sleep on some days and slightly better REM on some days. He reports "I have 92 nights of data where I tracked my sleep and whether or not I took potato starch. Of the nights when I took potato starch, my average sleep was slightly higher (6.5 hrs vs 6.3 hrs)." When he used lower doses paradoxically sleep might have been even longer but he had only a few data points (n=8) and couldn't conclusively say at this time.

Several potentially adverse changes occurred on the gut profile I noticed as we have seen on previous studies involving use of Bob's Red Mill potato starch (Folz family AmGut -- higher blood sugars on RUMPSan episode of fat gain/higher blood sugars/gout/NASH with long use 1.5 yrs on RUMPS). 


One of the most debilitating factors for a gut is to lose diversity. Antibiotics cause fat gain or lead to modern diseases because they lower gut diversity. The same species that keep us lean and immunoprotected are the same ones rapidly killed off by broad spectrum antibiotics. To make a dysbiotic gut model in rodents, scientists can give 5 round of antibiotics and a single round of Clindamycin to give you an idea how simple and easy it is. Microbiota 16S rRNA studies tell us that low diversity in the gut is the hallmark for a poorly functioning gut, one that is vulnerable to infection and inflammation (Le Chatelier et al, Nature 2013). 


36% Loss of Species
40% Loss of Orders
Depletions and Extinctions
Associated with "Raw Potato Starch"







In the first May sample, Sprague reports that 49% of the species were known and identified by uBiome, then as many as 65% were for the Oct sample. With dramatically less diversity and species, more species were known and identified, including some known toxin-secreting strains. For the orders, it was worse. The diversity destruction included 40% loss of known and identified orders from initially 45 orders down to only 27 orders. That is a lot of ecological devastation it appears. With high dose of a singly sourced 'fiber' or food, this is what occurs. The SAD (Standard American Diet) does the same thing, providing little in terms of nourishment and spectrum of fiber to the gut flora. Many species perish and so do the functions that they serve us with. Our gut flora are the silent organ that provides 10-15% of our energy, make dozens of vitamins and anti-cancer chemicals and keep us lean and healthy.

What extinctions did Sprague's gut appear to go through? Some good and some bad. The appearance of significant toxin-bearing strains (including Clostridium botulinum) might be notable as this is the 2nd case I've seen now associated with raw starch utilization.









Source Tap et al EM 2009
Principal coordinate analysis of OTUs from the faecal microbiota of 17 healthy human individuals. A principal coordinate analysis was performed using the full distance matrix. Each OTU was pictured as a disk whose area was proportional to the number of sequences and the heat colours accounted for the prevalence among the 17 individuals. Operational taxonomic units represented by a unique sequence (singleton) were not plotted.



The Gut Landmarks on uBiome Stool Analysis That Signal Good Health 

The landmarks that I look for are based on research by Tap et al and gut researchers on 4 different continents who have characterized the gut species found in abundance in healthy controls. I call these the 'ancestral phylogenetic core microbiota' since these are also found in abundance in rural living and ancestrally living individuals such as the Amerindians, Burkina Faso, Hadza and Malawai inhabitants. The above is a PCA showing the most prevalent OTUs that are hallmarks of health I believe. When I look at the gut profile of a healthy person, these are the ones I always find.

Faecalibacterium prausnitzii is very special. It is a gut barrier and immune system warrior and known as a keystone 'Peacekeeper' (Nature 2015, fantastic photos).You can see above it is a red-orange and found in robustly in concentration of hundreds in 94% of tested healthy subjects. In clinical trials, it is low where diseases are present and high in disease-free people. It is a harbinger for bad health if it and several other 'ancestral core' species are depleted. Moises Velasquez-Manoff recently wrote an essay outlining all the unique and protective aspects about F. prausnitzii and why all guts need it: SciAm "Among Trillions of Microbes in the GUT, a Few Are Special". Check out Gut Guardians in April, Moises will be a guest on our podcast with my co-host Matt Pepin!

How does Sprague's QS experiment stack up? Unfortunately after amputating over 1/3 of his gut species, many of the phylogenetic core are depleted. The initial levels were awesome but after a high dose of single source of 'fiber', many on re-testing were gone and dramatically diminished numbers.



The Problem with Depletions... Where's the Faecalibacterium prausnitzii??


Notable known species depletions associated with 40% reduction in orders (read more about each species HERE and poss consequences of loss). This pattern is a hallmark for raw starches (which are not part of human native diets; only #gerbilfood). The same pattern I've reported earlier and why leaders in ourpaleo blogosphere considered avoiding it -- here.
  • 17-fold reduction Faecalibacterium prausnitzii (only on species found in Faecalibacteria); how to raise F praus here; F praus doesn't eat starch at all, preferring to selectively dine on oligosaccharides, pectin and other varied non-starchy fermentable fibers
  • 50% Roseburia, major human butyrate producer and keystone immunity protector
  • 7-fold reduction Christensenella, potent fat burning species
  • 4-fold reduction Akkermansia, keystone mucosa lining protector
  • 14-fold below optimal Bifidobacteria longum, majority fecal bifidobacteria species and keystone immunoprotective species for babies and adults (optimal: 45% of total fecal bifido)





The Dysbiotic/Disease Gut Microbial Fingerprint

In several studies now, the gut microbial fingerprint has been characterized. Invariable they all look similar in many respects:
--low diversity
--depletions of known and identified 'good flora'
--overgrowths of known and identified potential pathogens

Sprague's gut like many on the potato starch has now taken on this profile. The loss of important immunoprotective species such as Faecalibacterium prausnitzii (17-fold depletion) is probably not a good sign. Further depletions of other known and characterized species associated with longevity and good health has also been decimated. The destruction of diversity perhaps has led to the emergence of a couple of pathogens that Sprague's gut didn't have earlier. His diet sounds varied but his reported fiber intake is somewhat low and suboptimal (15-20 g/day).

For Sprague 4 clostridium species were shifted signficantly by the experiment, I noticed. Two potentially pathogenic strains shifted down in abundance and two worst strains grew robustly and appeared to take their places.

Clostridium asparagiforme -- became extinct or undetectable.

Clostridium clostridioforme -- lowered by 50% which I think is an improvement

Clostridium baratii 0.55877%-- 5-fold increased, may secrete toxins similar to botulinum. Note: the concentration and abundance of this strain is higher than the phylogenetic core Bifidobacteria longum (0.18584%; 3-fold less, mmmmhhh...The pathogen is outnumbering a potent gut guardian)

Clostridium botulinum Ba4 str. 657 (0.00253%) -- new appearance to detectable levels of the Toxin B secreting strain isolated from a botulism case. Let's say our stools represent 10-100 trillion bacteria in the GI tract, therefore 0.00253% may be a proxy for 0.25 to 2.5 billion Clostridium botulinum bacteria in the gut. I don't think that is a trivial amount, sadly, if the data is semi-reliable. Researchers report that toxins from Clostridium are several thousands-times more toxic than other endotoxin releasing opportunistic pathogens in the human gut and considered one of our planet's most neurotoxic chemicals. Botulinum B toxin interferes with neural transmission of release of acetylcholine, key neurotransmitter in our calm and restorative nervous system (PSNS) and can lead to muscle paralysis (Nigam et al 2010). Botox for use in wrinkles is A toxin and stronger than B toxin. In Asperger's/Autism Spectrum individuals, Clostridium and other gut pathogens (Enterobacter, Sutterella, Desulvovibrio) and low gut guardians (Eubacteria, Lachnospiracea [Coprococcus, Roseburia intestinalis, Roseburia faecis], Bifidobacteria) appear to form a unique microbial signature  (De Angelis et al 2013; Midtvedt 2012).  RUMPS-raw potato starch appears to create this hallmark Aspie/autism signature.

BIONIC FIBER (Column 3) ASSOCIATED
WITH LOWER CLOSTRIDIUM

Emergence of Several New Pathogens With 'Raw Potato Starch' in Sprague's Sample

Let's detail the the species that appeared to emerge in Sprague's QS n=1. Sprague reports no digestive issues or health problems. His HgbA1c pre- and post-test is still acceptable 5.0% and sleep/mood/energy/skin/digestion all remain good.

Clostridium botulinum 
Known and identified Toxin B secretion strain Clostridium botulinum Ba4 str. 657
  • http://www.ncbi.nlm.nih.gov/bioproject/29077
  • This strain was isolated from an infant botulism case in 1976. The strain is a bivalent Ba strain, that simultaneously produces two different toxin types 
  • C botulinum some strains also appear to be hefty starch and sugar eaters (Macfarlane et al 2000 AEM). Many of the clostridiums are. They are ancient primordial survivors. Some good for us but some not so.
  • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC92288/pdf/am004212.pdf




Clostridium baratii
Another Clostridium is associated with inflammation and autoimmune dz like Kawasaki's. C baratii appears 5-fold higher compared to the initiation of the experiment.



Clostridium clostridioforme
High Clostridium clostridioforme which is associated with diabetes, low gut diversity, inflammatory conditions and human invasive and severe infections like bacteremia. Often it produces alcohol and other toxins, which are associated with inflammation, artery hardening, and histamine responses. Alcohol from microbial fermentation results in blockages of multiple enzyme pathways in the host including the degradation of histamine. When more histamine accumulates, subsequently, the host has more allergic reactions, congestion, rash, headaches or other manifestations of high histamine. These are all secondary to a dysbiotic and imbalanced gut.


Raw RS2 selectively appears to increase toxic, adhesive E coli and Clostridium in both small and large intestines




Person "A" and Amped-Bionic Fiber is Associated with Lower Toxic Clostridium Levels

In this series of posts, 4 uBiome analyses will be reviewed. The third column in the above comparison is of a gentleman who was also on potato starch 2-4 Tbs for 6months, then switched to an 'amped version' of Bionic Fiber for 4 months. Besides Sprague's example, Person 'A' is the second case of associated potato starch-enrichment of Clostridium botulinum.

On the other hand, Bionic Fiber is associated with reduction of Clostridium strains per studies (see below). I think now, Person 'A' is on a downtrend for Clostridium.

Person 'A' reports numerous improvements since starting Bionic Fiber: better sleep, better skin, better brain (decreased fog and fatigue).

BENEFITS OF AMPED BIONIC FIBER: Bionic fiber is a combination of diverse fibers that the gut flora absolutely thrive and love to eat. It works because they selectively stimulate nearly all the phylogenetic core that Julien Tap et al and gut researchers around the world have identified as the core consortia that protect human health for millenium as observed in both individuals that still live non-urbanized 'dirty' living and those that live in Europe, Korea, and USA. The basis of bionic fiber discussed here. For vital 'Peacekeepers' like Faecalibacterium prausnitzii and super immunoprotective gut flora, it potently stimulates these colonies along the length of our guts for human leanness and longevity.

Velasquez-Manoff, Nature 2015


Person 'A' took for four months prior to the uBiome sample an amped version of BIONIC FIBER inulin, acacia, glucomannan, psyllium, baobab fruit powder and larch arabinogalactan.

Inulin, GOS, FOS and other oligosaccharides purge pathogens like toxin-secreting Clostridium strains


Butyrate looks like it is quite good with really high Eubacteria, Ruminococcus, Lachnospiraceae and other Clostridiales being robust and abundant (we'll review in detail in future posts). These are higher than Sprague's initially and post-potato parade.

According to Person "A":
"So about 3 years ago started having somewhat generic symptoms - brain fog and fatigue, dry/flaky skin mostly on my face. Switching to a perfect health diet (or at least trying to follow PHD [PERFECT HEALTH DIET, PAUL JAMINENT) helped quite a bit. [Fiber]: 15-20 grams of fiber per day on average. We eat a good amount of rice and potatoes, some freshly cooked, some cooled and reheated. Probably average 1 serving of vegetables a day (mostly broccoli, brussel sprouts, green peas) and 2-4 servings of fruit per day (bananas and berries mostly). We've also been re-incorporating beans lately - probably 2-3 servings per week.

I started RPS about 1 year ago and quit almost immediately due to some joint pain and excessive gas. A few weeks later I tried again, but started with a much smaller amount and built up to the 2-4 tbsp/day recommendation at the time. I didn't notice much of a difference, other than really great bowel movements - very regular and consistently a bristol 3 or 4. The brain fog and fatigue continued to be occasional - no real change with just the RPS.
Then about 4 months ago I started mixing up your bionic fiber, dumped the RPS but still used some plantain flour. I'd say I get about 20-30 grams of supplemental fibers a day now, with inulin and acacia being the majority. Glucomannon, psyllium, baobab, larch are included as well in very small amounts. I've now dropped the raw plantain flour in the last couple weeks.
Since switching to the bionic mix, here the changes I've noticed. Bowel movements slightly worse actually. Still fairly regular, but get bristol 2 every now and then. Brain fog and fatigue still present, but noticeably improved. Skin appears to be healing as well, but not all the way there yet. Skin is improving - dryness, texture, moisture. I'm not really sure how to describe it and my doctor never thought it was anything to worry about - he just said to use lots of moisturizer... It wasn't painful or itchy, just unsightly to look at!"



To Be Continued...

We'll talk more about
--Bifidobacteria longum
--how Bionic Fiber bionically raises buytrate producers

4 comments:

Unknown said...

Hi. Great article!

I really need some help and guidance. Through breath test, Great Plains testing, and colonoscopy, I know I have ulcerative colitis, breath test positive (sibo), had some mercury and aluminum slightly high. So test are old and some new. No doctors know what to do with the info or test but being a RN I was able to have my own acct with Great Plains and order my own test. Could I post these test and could some give advice? I am asking for the advice please! If I can post, is there a certain way to upload my results?

Some things to point out from the test- Oat test showed high clostrium species, high bacterial numbers, low vit c, high vit b6.
Stool test showed high lactoferrin, lysozyme, and IGA- all were very high. Immune system is overdrive working which is why I think I have zero energy, always tired never can sleep, skin rashes like crazy, poor healing, hands and feet always ice cold...( this really scares me as my arteries may be bad??)

My gut is all over the place- blood mucus constipated diarrhea bloated losing weight skinny...

Can't breathe out of my nose always stuffy but runny to, ears itch inside bad, ear wax (can not understand this), skin on face is dry, but oily too, I get blackheads bad and skin can't breathe causing blackheads to turn to keratin balls? It's weird neve seen anyone else with this skin issue ever! Bad dandruff and keratin in hair too but no where else on body.

I know everything is tied to my gut but noting helps- I'm 32 year old, a male, and 8 years ago before this started abruptly, I was healthy never sick felt amazing. Yes I've used antibiotics like crazy before I was sick, but when I actually got sick I was healthy and felt great, but boom it came outta no where and never got better!

Thank you!!


Dr. B G said...

Freak,

Person 'A' and I will be discussing what we do in a couple of weeks. My practice is full but you can try contacting me later -- or consider referral to John Brisson (see last few Gut Guardian podcasts).

Cheers
G

Anonymous said...

Freak I have exact same skin and scalp issues so u r not the only one. Grace is there a waiting list I can be put on for a consultation? I have a nutreval by gdx results and wAiting for doctors data stool test now and 23 and me results. Would love some help.

clark ellis said...



The absence of those keystone species is what is worrying me about my gut at the moment. I have made progress the last year with my gut, and don't have any major worries with bad bacteria, but I agree with what you're saying about those keystone species. I have no R. intestinalis, E. rectale, R bromii, B. vulgatus and I wonder, will I ever get them back?