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.