A post from a reader on microbiome mechanism

Ben posted this on an earlier post, I thought that it should be presented as a reader post.

This article may be of interest:

The researchers identified a new mechanism where repeated exposure to typical food poisoning pathogens lead to a chronic disease state that did not resolve by itself, even after the pathogens were cleared, and even if the levels of pathogen were less than is needed to produce acute food poisoning symptoms (so the hosts may not have been aware).
The mechanism is to do with an acquired deficiency of an important gut inflammation mediating enzyme – called Intestinal Alkaline Phosphatase ( IAP)

Without this enzyme, the host is unable to deal with normal bacterial toxins from even beneficial microbes in the gut, and a cascade of damaging inflammation is created in a self-perpetuating cycle.

  • This leads to a big list of symptoms that are a pretty good match to much of what is described in CFS
    •  Inflammation of Colon and Small Intestine
    • Leaky Gut (small intestine membrane permeability)
    • Weight loss (likely indicates malabsorption)
    • diahrea (or altered bowel habit)
    • faecal blood – and prolapsed anus
    • colon shortening
    • systemic inflammation (host of inflammatory cytokines are increased by up to 26 fold)
  • It’s pretty easy to see this might lead to further symptoms in a chain of events
    • disrupted metabolism (due to systemic inflammation, oxidation etc )
    •  fatigue ( due to malabsorption, leaky gut or systemic inflammation etc)
    •  allergy / food sensitivity ( due to gut permeability)
    •  systemic cell aging – neuraminidases are known to regulate the aging of various enzymes and cells in the body
    •  hormonal / sympathetic nervous system disorders – again from systemic inflammation (dysregulated sleep, blood pressure, temperature, mood, etc
    •  neurological disorders – again from inflammation, dysbiois (memory, cognitive function, etc etc )
    •  clotting disorders – Neuraminidases are known to interfere with both cell membrane and clotting mechanisms

I mention it here as it’s a possible explanation or underlying model describing the experiences discussed here.

The fit seems very good.

Interestingly the condition also causes the host to lose control of the gut microbiota population resulting in imbalance in the proportions of beneficial and pathogenic strains. Further re-enforcing the cycle – and would match many of the gut symptoms reported by sufferers. And echo the Ubiome reports of people here.

Neuraminidases are also known to cause disruption of the clotting mechanisms in humans – so this could explain the link to red blood cell morphology in CFS sufferers and sticky blood as discussed here.

It would also explain the prolonged ‘Herx’ reactions that many sufferers report. When the mainstream view is that any true Herxheimer reaction lasts only a few days as microbes in the blood are killed. But, if an overactive immune response to the LPS toxins of microbes in the gut is responsible then we would indeed expect a long-term reaction as it is just not practical to kill all bacteria in the gut with these treatments.

Also – in another interesting avenue; Neuraminidases are used by viruses to multiply their infection rate in the host cells. In fact, Anti-viral drugs for Flu e.g. Tamiflu are neuraminidase inhibitors. This could potentially therefore be an explanation for CFS sufferers becoming susceptible to infection with and developing chronic forms of viruses such as EBV, CMV, Herpes Simplex etc. that other people clear (as described by many Physicians specialising in CFS, Eg Myhill, Cheney etc.). As higher circulating neuraminidases may benefit viruses and hamper the human immune system.

Finally, CFS is common, at over 1% of the population by most counts, so whatever causes it is more likely to be something that lots of people are exposed to like mild food borne pathogen exposure – rather than some rare pathogen that few people will be exposed to. So, it fits with the epidemiology.

The researchers prevented the condition developing with co-commutant supplementation with additional IAP – or a neuraminidase inhibitor. Both worked well, leading to the question of whether neuraminidase inhibitors – either natural forms (btw. I think turmeric may include them) – or pharmaceutical, could be useful in reversing CFS with gut symptoms in humans. Or IAP for that matter – there are some human trials of it in IBD already.

There is a summary here http://science.sciencemag.org/content/358/6370/eaao5610
Or the full study text here http://nizetlab.ucsd.edu/Publications/Gut-Inflammation.pdf

The study is in mice – so the usual provisos apply.

I wasn’t sure where was best to post this – but since Giardia is a gut pathogen i thought this would work – but feel free to move it.

I would be interested in others thoughts.

Intestinal Alkaline Phosphatase

  • ” IAP is an endogenous protein expressed by the intestinal epithelium that is believed to play a vital role in maintaining gut homeostasis. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. As these events are a cornerstone of the pathophysiology of many diseases relevant to surgeons,” [2016]
  • “The present review analyzes the earlier literature on the dietary factors modulating IAP activity in light of these new findings. IAP regulates lipid absorption across the apical membrane of enterocytes, participates in the regulation of bicarbonate secretion and of duodenal surface pH, limits bacterial transepithelial passage, and finally controls bacterial endotoxin-induced inflammation by dephosphorylation, thus detoxifying intestinal lipopolysaccharide. Many dietary components, including fat, protein, and carbohydrate, modulate IAP expression or activity and may be combined to sustain a high level of IAP activity. In conclusion, IAP has a pivotal role in intestinal homeostasis and its activity could be increased through the diet. This is especially true in pathological situations (e.g., inflammatory bowel diseases) in which the involvement of commensal bacteria is suspected and when intestinal AP is too low to detoxify a sufficient amount of bacterial lipopolysaccharide.” [2010]
  • “Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP’s role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP’s ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP’s ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP’s ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery.” [2014]

SelfHacked.Com has an interesting post on this.


FYI, if you tried to…

FYI, if you tried to upload your uBiome in the last day and failed, please try again — there was a bug that has been fixed.

Comparing repeated uBiome results

There are some 15 readers who have done 2 or more uBiomes. I have added a new page to allow the people to see differences better.

After login at:  http://ubiomecfsweb.azurewebsites.net/Biome/login a new choice will appear if you have done 2 or more uBiome:


Click this take you to a page to select which ones you wish to compare:


Selecting and clicking will take you to a page which will compare:

  • Symptoms
  • Function/Metabolites
  • Bacteria


Comparing Function/Metabolism


Comparing Bacteria


Bottom Line

This tool will hopefully help with understanding how you have manipulated your microbiome by changes in diet, supplements, antibiotics and probiotics.

If you find interesting changes, feel free to post as a comment here.

Microbiome Site Update – POTS and ALA

Contributed data to the site consists of:

  • 112 ubiome results uploaded from 90 different people
    • 49 of these have had symptoms added, 40 had general fatigue
    • 29 of these have had metabolites added (from ubiome site)

Observations for General Fatigue(40)

  • 60% with unrefreshing sleep

Metabolite Function

With 65% either high or low

  • Amino acid metabolism: D-Arginine and D-ornithine metabolism LOW
  • Bacterial Abilities: Bacterial chemotaxis LOW
  • Bacterial Abilities: Flagellar assembly LOW
  • Secondary metabolite degradation: Toluene degradation JHIGH

Bacteria Class

Bacteria Order

Genus Level

Observations with Fatigue with Unrefreshing Sleep

Metabolite Function

With 65% high or low

  • Amino acid metabolism: D-Arginine and D-ornithine metabolism Low (81%)
  • Lipid metabolism: Steroid hormone biosynthesis High (72%)

Following had more than 65% high:

Following had more than 65% low

Postural orthostatic tachycardia syndrome (POTS)

Metabolites with 65% high or low

  • Amino acid metabolism: D-Arginine and D-ornithine metabolism Low (85%)
  • Bacterial Abilities: Bacterial chemotaxis Low (76%)
  • Bacterial Abilities: Bacterial motility proteins Low (68%)
  • Bacterial Abilities: Flagellar assembly Low (76%)
  • Bacterial Abilities: Lysosome High (68%)
  • Lipid metabolism: alpha-Linolenic acid metabolism Low (76%)
  • Lipid metabolism: Steroid hormone biosynthesis High (76%)
  • Secondary metabolite degradation: Chlorocyclohexane and chlorobenzene degradation High (76%)


Bottom Line

While our sample sizes are small, we do note some potential difference between those with general fatigue and POTS. Specifically:

  • Pseudoflavonifractor and Streptococcus are more dominant and several others are less
  • Lipid metabolism: alpha-Linolenic acid metabolism Low (76%)
    • Suggests that supplementing with ALA may help
    • I could find no studies using this supplement.
  • Bacterial Abilities: Bacterial chemotaxis being low (poor communications/movement between cells) may be a significant factor for POTS.

The purpose of this post is to show how it is possible to identify metabolites and bacteria that are associated with certain symptoms (and in this case, for POTS, identify a supplement that may potentially help).


This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.



Should you do uBiome before going on Antibiotics?

A reader on a local CFS group asked:

Ken Lassesen, can I enlist your expertise and help? First, I’ve been enema-dependent for a few years and I’m wondering if my Ubiome might give you some fascinating info. Second, I’m going to treat SIBO soon with vancomycin and Rifaxamin and I haven’t had antibiotics in many years — before being sick with ME. Could this give any interesting or helpful info (either for you or me) – if I did a Ubiome before and after treatment? Thanks for the help!

The Answer is very much a yes. Each of these antibiotics cause significant changes — the question arises — will the net change be for the better or the worst?

The following is the information (with sources) that have been assembled so far. I have seen some CFS patients with high Proteobacteria thus Rifaximin would be good, but not vancomycin. For other patients, the opposite is true.










Bottom Line

Most studies deal with a sample of patients that presents a condition.  The group as a whole may have positive results but individuals may not.  Working off your own uBiome may allow your likely response to be better predicted. More individual treatment based on your own reality.


This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.

Gut Bacteria associated with Restless Leg

The following profile seems to occur with restless leg according to our explorer:

With high genus Oscillibacter being seen often.


The following should improve the bacteria shift seen above:

Walnuts 3.03
barley 2.02
Choline 2.02
Polymannuronic acid 2.02
Pomegranate ellagitannins 2.02
Bifidobacterium infantis 1.01


Acetic acid -2.02
Aspartame -2.02
Choline deficiency -2.02
Doxycycline -2.02
high-fat diet -2.02
Isobutyric acid -2.02
Isovaleric acid -2.02
macrolide -2.02
saccharin -2.02
vancomycin -2.02
vegetarian -2.02

Bottom Line

The following are likely to help

  • Supplement with choline
  • Eat Walnuts and Pomegrantes
  • Barley porridge

Do not use Saccharin or Aspartame

This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.

Dioxin degradation and CFS

For the third item from the Metabolite Explorer, we return to a LOW item, Secondary metabolite degradation: Dioxin degradation. Here we see

  • Low 8/14
  • High 1 /14
  • Normal 5/14

We all know the term dioxin and usually associate with man-made evil chemicals associated with PCBs. This reduced ability to degrade dioxin may means increase culmination of dioxin in the body for some (not sufficient clearance for the intake).

“The terms ‘dioxins’ and ‘dioxin-like compounds’ are used in literature when referring to a large family of chemical compounds that are found in trace amounts in nearly all realms of the environment….Dioxins are the byproducts of both anthropogenic activity and natural processes. “[src]

What is the main source of dioxin in the environment, according to the EPA, Backyard burning of refuse accounts for 35%!

The World Health Organization(WHO) writes

  • “Dioxins are found throughout the world in the environment and they accumulate in the food chain, mainly in the fatty tissue of animals.
  • More than 90% of human exposure is through food, mainly meat and dairy products, fish and shellfish.
  • Once dioxins enter the body, they last a long time because of their chemical stability and their ability to be absorbed by fat tissue, where they are then stored in the body. Their half-life in the body is estimated to be 7 to 11 years. In the environment, dioxins tend to accumulate in the food chain. The higher an animal is in the food chain, the higher the concentration of dioxins.
  • Long-term exposure is linked to impairment of the immune system, the developing nervous system, the endocrine system and reproductive functions.
  • Trimming fat from meat and consuming low fat dairy products may decrease the exposure to dioxin compounds. However, the possibility for consumers to reduce their own exposure is somewhat limited.”

Some Literature

Bottom Line

If you have a low Dioxin degradation, then the best information appears to suggest:

  • Reduce food and supplements (i.e. Fish Oil, some Omega-3 and 6) higher in dioxin. Trim fat off meat. Low fat dairy products.
  • Resveratrol supplementation
  • Folic acid supplementation
  • Activated charcoal

Do not expect quick results. To reduce half of the existing dioxin is 7 to 11 years, with a low degradation it may be even longer without some of the above.

This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.