Fecal Matter Transplants and Phages

FMTs have been tried for Chronic Fatigue Syndrome/ME with mixed success. The why of failures has been an ongoing interest of mine. We may now have a significant factor that has been ignored in these attempts.

 Fecal microbiota transplantation (FMT) as a special organ transplant therapy, which can rebuild the intestinal flora, has raised the clinical concerns. It has been used in the refractory Clostridium difficile, inflammatory bowel disease, irritable bowel syndrome, chronic fatigue syndrome, and some non-intestinal diseases related to the metabolic disorders. But this method of treatment has not become a normal treatment, and many clinicians and patients can not accept it. 

[Research progress of fecal microbiota transplantation] 2015

This week’s Economist had an extended essay on Viruses and the like: The aliens among us/The Outsider within, this provides good background.

In addition to this, there was a podcast reporting success with FMT was associated with higher Phage Diversity in the donor. Phages are the police of the microbiome.

In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.

The success of fecal microbial transplantation in Clostridium difficile infection correlates with bacteriophage relative abundance in the donor: a retrospective cohort study (2019)

My earlier posts on FMT

Bottom Line

This implies that for a greater chance of success and less risk, than DYI fecal transfer, that a lab that tests for possible infections AND for phage state may yield the best results.

Comparing Taxons on same FastQ file

David Morrison requested this feature. The FastQ file is produced by the physical lab machine. This file is then pushed thru software to produce a list of taxonomies. Different 16s retail providers use different software and as a result – different reports. For back ground see this “Taxonomy Nightmare before Christmas” post.

Walkthru

This feature is available only for those that sign on securely (i.e. request a login link to be sent by email).

On the samples page you will see some new buttons

Items are disabled if you use legacy login
Buttons enabled with secure login

Define FastQ files

Simply Click [FastQ Catalog] and create records for each FastQ file you are going to work with.

Identifying sample with FastQ file

Return to the Samples page, and click [Update of Delete Samples]

You may now assign the FastQ file to the sample intrepretation

Comparison

You need at least 2 sample to be linked to a FastQ file. Returning to the Samples page, click the [FastQ Set Comparison] button

Select the FastQ file that you are interested in, click Compare button.

You will now see the results reported. Some taxonomy will be very similar and others very different.

What’s next?

Once sufficient users link their files, we can start doing the various analysis that David was asking for.

Post-Covid19 Syndrome

Most of the Post-Covid19 Syndrome symptoms has a strong match to the symptoms seen with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This condition has no conventional medical treatment known. Treatments attempt to mitigate symptoms.

There is evidence that some people develop a long-term fatigue syndrome from coronavirus infections, Dr. Anthony Fauci said Thursday.

“There may well be a post-viral syndrome associated with Covid-19,” Fauci told a news conference organized by the International AIDS Society. The group is holding a Covid-19 conference as an add-on to its every-other-year AIDS meeting.

Fauci said the symptoms resemble those seen in patients with myalgic encephalomyelitis, or ME, once known as chronic fatigue syndrome.

“If you look anecdotally, there is no question that there are a considerable number of individuals who have a post-viral syndrome that in many respects incapacitates them for weeks and weeks following so-called recovery,” Fauci said.CNN

I am very familiar with ME/CFS as anyone who knows my story can attest. And I believe that while the model of why these symptoms are there is simple, the treatment is complex, not cookbook and must be individualized for each person.

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Persistent Symptoms in Patients After Acute COVID-19

The Model

COVID19 sends out chemical signals to the body to produce chemicals (metabolites) that its need OR which create a friendlier environment for it. The signals alters the microbiome (gut bacteria) to be a factory for its needs (Viralforming the gut). Once COVID is eliminated, the alterations should return to the prior state overtime— unfortunately a percentage that take a long time or never return. The best documented example is the Bergen’s Giardia Infection.

“Gastrointestinal symptoms are common in patients with COVID-19, and had an increased prevalence in the later stage of the recent epidemic in China. SARS-CoV-2 enters gastrointestinal epithelial cells, and the faeces of COVID-19 patients are potentially infectious.”Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission

The microbiome consists of many co-operations between bacteria. Often there are over 2000 bacteria involved in various dialogs. Identifying the bacteria that are at abnormal (too high or low) is the start. The next step is modifying the bacteria by drugs, diet, supplements. At this point, we need to point out that there may be 100 or more abnormal bacteria that needs to be adjusted. Naive adjustments may make more bacteria abnormal.

My Proposed Process

This is the process that I have done with ME/CFS and it is likely that it may also work for many people with post-covid syndrome:

  • Obtain a 16s analysis from an appropriate source
  • Look at the suggestions for correcting and make appropriate changes
  • Two+ weeks after making changes, repeat the 16s analysis and make the next set of changes.

This is an iterative process. Often the suggestions will cause one symptom to lessen or disappear while leaving others untouched. This is to be expected.

For more information, see

BiomeSight (UK) is now integrated with Microbiome Prescription

Rose Walbrugh and I are proud to announce one click sending of data from BiomeSight.com based in the UK to MicrobiomePrescription.com. After you get your BiomeSight data processed, you can send the data across without needing to download and upload. You will be sent an email with an automatic login link (no more making up and remembering passwords!).

The transfer is available as an external application on a mobile device, as shown above
Or with more details in a web browser.

Once the [Send] button is clicked, you will get an email like shown below that allows you to login and explore your data deeper.

Clicking the link will log you in automatically, and you will see your sample and it’s identified as originating with BiomeSight.

BiomeSight specific distributions of bacteria will automatically become available once there is a large enough sample.

DISCOUNT CODE

As part of this celebration, a discount code “MICRO” is offered on BiomeSight services. This results in £60 off, which brings the price down to £89 per kit ($110). Local USA fulfillment is now setup. Expedited 2 day delivery at £4.95.

Bottom Line

Microbiome Prescription is dedicated to working with labs to enrich user experience and knowledge. BiomeSight has stepped up to the plate for cooperation and win-win attitude.

The pain of Lab Hierarchies

I am currently working with BiomeSight.com to add Taxon numbers to their downloadable reports.

At first sight, this should be easy, the sample of their complete taxonomy looks like this:

The problem is that their software have forced items into an unnatural structure to make presentation easy. An item that is under Class — when you go to NCBI Taxonomy Browser may be listed as:

  • Sub-Class
  • Super-Class
  • Order
  • Sub Order
  • Family

The result is that many many items have to be resolve by manual inspection of NCBI to find the apparent match and individually assigned. Example below, notice the “Group II” item which required working from existing matches for a line to identify probable candidates.

Update [MicrobiomeSight] Set OID=2731342 Where [Order]='Group II'
Update [MicrobiomeSight] Set OID=1643688 Where [Order]='Leptospirae'

Other issues concern differences of spelling and renaming, i.e. Cerasicoccales vs Cerasicoccus that was found….

While NCBI shows

We have a possible old/atypical name being used which obtuficates reports. This is one of the key reasons that I am pushing for taxon numbers in all uploads because without them, we would have massive inconsistencies.

After getting all of the Genus and Above resolved, I hit an issue with the species.. namely the list shown below remain unresolved. A few I did a google for and found no hits. Many had incomplete names.

Example:

Bacillus polyfermenticus in NCBI is Bacillus velezensis variant polyfermenticus
  • Acholeplasma ales
  • Burkholderia eae
  • Candidatus Methylacidiphilum infernorum
  • Cryocola poae
  • Dechloromonas fungiphilus
  • Desulfovibrio aceae
  • Enterobacter aceae
  • Enterobacter rottae
  • Erwinia dispersa
  • Haererehalobacter salaria
  • Haloterrigena gari
  • Herpetosiphon agaradhaerens
  • Megasphaera geminatus
  • Mycobacterium indicus
  • Oscillospira eae
  • Tessaracoccus terricola
  • Pasteurella eae
  • Stenotrophomonas retroflexus
  • Stenotrophomonas griseosporeus
  • Trabulsiella farmeri
  • Vibrio bacterium

Bottom Line

All Phylum, Orders, Classes, Families and Genus had matching taxon assigned. At the Species level, 6445 were identified and 21 were not. This means 99.7% of species were given taxon numbers. I expect BiomeSight.com to offer uploadable formats soon, ideally with automatic transfer from their web site.

Preventing Antibiotics Diarrhea

I just got out of the hospital for cellulitis where I was treated with IV antibiotics. My discharges notes said “take antibiotics to prevent diarrhea”. I asked which ones… blank faces. No one seem to have a concrete idea. So this is a review of the literature:

If you find any other studies that is explicit on the probiotic strains used with good results, please email me at Ken/at\lassesen.com

To help find which probiotics contain the above see this page.

Pycnogenol and Allergies/Mast Cells

A reader asked about this, which I have no covered yet. Increased allergies and mast cell issues often occur with microbiome dysfunction and chronic fatigue syndrome.

Bottom Line

The research to date suggests that it may take 2 or more months before significant benefits may be seen in some cases.

Symbioflor-1 A sinus probiotic

“The probiotic Symbioflor 1 is a historical concoction of 10 isolates of Enterococcus faecalis. Pulsed-field gel electrophoresis revealed two groups: one comprising eight identical clones (DSM16430, DSM16432, DSM16433, DSM16435 to DSM16439) and a further two isolates (DSM16431, DSM16434) with marginally different profile” [2016]

“A double-blind, placebo-controlled multicenter study in 157 patients with chronic recurrent sinusitis investigated the occurrence of acute relapses during treatment of patients with a bacterial immunostimulant (3 x 30 drops/day), comprised of cells and autolysate of human Enterococcus faecalis bacteria (Symbioflor 1, n = 78) in comparison to placebo (n = 79)…. the occurrence of relapses (50 incidents) was about half (56%) the number observed under placebo (90 incidents)” [2002]

“the time span until occurrence of the first relapse was clearly longer under verum[Symbioflor-1] (699 days) than under placebo (334 days) and after the end of the observation period 91% of patients under verum experienced only one relapse compared to 62% in the placebo group (p = 0.01). ” [2001]

From PubMed

  • “Compared with the controls, probiotic intervention significantly upregulated the level of IL-10 and TGF-β, downregulated levels of IFN-γ, and increased progesterone level that reversed the trend of being Th1 predominance state ” [2020]
  • 1. E. faecalis stimulates the liberation of interleukin 1 (IL-1 beta) and interleukin-6 (IL-6) in a dose-dependent manner; the E. faecalis induced liberation of IL-1 beta and IL-6 is inhibited by dexamethasone (Dm) but not by cyclosporin A (CsA).”
    2. E. faecalis stimulates the liberation of gamma-interferon (IFN-gamma) in a dose-dependent manner, which is inhibited by both Dm and CsA.”
    3. Phytohemagglutinin (PHA)-induced liberation of gamma-IFN and interleukin-2 (IL-2) is inhibited by E. faecalis in a dose-dependent manner. ” [1994]
  • “For instance, Escherichia coli Nissle 1917 was a poor inducer of iNOS gene expression compared to the other E. coli strains, while Enterococcus faecalis Symbioflor-1 was more potent in this respect compared to all the eleven Gram-positive strains tested. ” [2014]
Symbioflor 1

Personal Experience

I have used this for sinus issues in the past and it has been effective in clearing them.

Source: https://www.paulsmarteurope.com/symbioflor-1-tropfen-drops-50ml/

Hafnia alvei 4597 Probiotic is available

A reader forwarded this to me with the following comment..

My mother is a health 58 years old women a little bit over weight she started to have after 2 weeks of use: headaches and feeling very fatigued so I think she has die-off, The interesting thing that happen she has swollen lymph nodes under her arm pits for about 25 plus years, the lumps started to regress, I cannot find the microbiome condition associated with this and this strain of probiotic she started to use.

Entero Satys

This is available from France. Link here. International availability is unknown. “Hafnia alvei is a psychrotrophic bacterium, it originates in raw milk and continues to grow in cheeses such as Camembert.  abundant levels of Hafnia alvei can be found in raw milk cheese ” [Wikipedia]


Ingredients:
 Corn starch; coating agent: hydroxypropylmethylcellulose; freeze-dried bacterial strain ( Hafnia alvei 4597 ); gelling agent: gellan gum; zinc (zinc bisglycinate, glycine, acidifier: citric acid, anti-caking agent: silicon dioxide [nano]); anti-caking agents: magnesium salts of fatty acids; chromium (picolinate).

Research

Hafnia alvei HA4597 Strain Reduces Food Intake and Body Weight Gain and Improves Body Composition, Glucose, and Lipid Metabolism in a Mouse Model of Hyperphagic Obesity 2019

  • “In conclusion, the present study showed that a daily provision of the H. alvei HA4597™ strain in genetically obese and hyperphagic ob/ob mice with HFD-exacerbated obesity decreased body weight gain, improved body composition, decreased food intake, and ameliorated several metabolic parameters, including plasma glucose and total cholesterol levels. “

Commensal Hafnia Alvei Strain Reduces Food Intake and Fat Mass in Obese Mice-A New Potential Probiotic for Appetite and Body Weight Management 2020

  • “Finally, the low abundance of ClpB gene expressing Enterobacterales species found in the microbiota of obese subjects in the present in silico analysis may indicate insufficient anorexigenic signaling from the gut microbiota to the host, further providing the rationale for supplementation of commensal bacteria expressing the ClpB protein with an α-MSH-like motif. “

Role of the Gut Microbiota in Host Appetite Control: Bacterial Growth to Animal Feeding Behaviour, 2017

Bottom Line

There was no detail microbiome information cited in studies above. The mechanism of operation was increase production of a metabolite from this bacteria that alters the number of meals.

The daily dosage is 50 million CFU ** / 100 billion cells, i.e. 5 x 10^7. Some (made in France) Camembert are reported to exceed this level in 1 gram (especially the surface).

It is available as a specialized cheese starter.