Category Archives: Conditions

Unknown's avatar lassesen 9:56 am on October 20, 2018  

Initial reflections on Cortene (CT38) drug.

My long time friend Cort Johnson has done four posts on this promising new drug for CFS/ME (and possibly other autoimmune conditions).

My own focus is the microbiome – keeping to a merging of concepts from Occam’s razor and Osler’s Principles. For a new drug that is just starting clinical trials, this presents a challenge.

The model behind this application is the HPA axis, hypothalamic-pituitary-adrenal axis. And specifically three items are cites:

  • Corticotropin-releasing factor
    • CRF1 – low stress,
    • CRF2 – high stress
  • Urocortin 1 (UCN1) – a 40 amino acid peptide that normalizes the above

What related information is on PubMed

Short Version

It appears to be established that CRF shifts are associated with issues associated with intestinal inflammation, gut permeability, and changes in the intestinal microbiota. There is a chicken-and-the-egg question. Did the microbiota change first and the others are consequences OR did things like gut permeability altered the microbiota. My working hypothesis is that the microbiota shift occurred first.

This may also explain why I seem to be able to recover from CFS/ME multiple times. My personality type has been evaluated as a Pollyanna, thus significantly less inclined to be stressed mentally, nor dwelling on the past and with a strong positive future perspective.

Bacteria links:

  • “Both CRF and UCN1 were significantly augmented by Bacteroides vulgatus and Fusobacterium varium at both the mRNA and protein levels. In particular, B. vulgatus stimulated human MoDCs, resulting in extremely high levels of CRF and UCN1. Conclusion: Stimulation of MoDCs by B. vulgatus and F. varium may be associated with CRF/UCN1-related intestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease.” [2014]
  • “. In conclusion, Lactobacillus rhamnosus GG (LGG)  stimulates IL-4, IL-10 and Ucn expression ”  [2010]

How does Cortene work is the question!

My first prediction is simple: it will alter the microbiome. If it’s main mechanism of action is the microbiome, then my second prediction is that will be effective for only a percentage of patients — why? Every patient have a unique, and frequently very different, microbiome.

“Cortene’s drug, CT38, is a CRF2 agonist, i.e., it stimulates CRF2. It is comprised only of amino acids that occur naturally in the human body.” [post]

Bottom Line

This drug is still in early stages and my gut feeling is that it will have limited success for a small number of people.  The CRF/UCN imbalance is very likely real — but my bet is on a microbiome shift being the maintainer and likely cause of this imbalance.

Unknown's avatar lassesen 7:36 am on October 18, 2018  

Estrobolome: Microbiome, estrogen and cancer

A reader asked me to do a research dive and post on Estrobolome. This is likely a new word for most of my readers as it was for myself.

” estrobolome, the gut bacterial genes capable of metabolizing estrogens in both healthy individuals and in women diagnosed with estrogen-driven breast cancer ” [2016]

or a more technical definition

 “the aggregate of enteric bacterial genes whose products are capable of metabolizing estrogens”  [2011]

This visual may put things is a clearer perspective: [2016 src]

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“Recent research suggests that the microbiota of women with breast cancer differs from that of healthy women, indicating that certain bacteria may be associated with cancer development and with different responses to therapy.”[2018]

 

The differences of genes determine what happens with estrogens.

  • “In the human GI tract, the BG gene is well represented in the bacterial phyla Bacteroidetes and Firmicutes whereas gus is more common in Firmicutes” [2012]

The technical details are  ß-glucuronidase and/or ß-galactosidase +, on which we have some basic taxonomy information [2012]

Genus ß-glucuronidase ß-galactosidase
Collinsella + —
Edwardsiella + —
Alistipes + +
Bacteroides + +
Bifidobacterium + +
Citrobacter + +
Clostridium + +
Dermabacter + +
Escherichia + +
Faecalibacterium + +
Lactobacillus + +
Marvinbryantia + +
Propionibacterium + +
Roseburia + +
Tannerella + +
Actinomyces — +
Alistipes — +
Anaerostipes — +
Bacteroides — +
Barnesiella — +
Bifidobacterium — +
Blautia — +
Butyricicoccus — +
Butyrivibrio — +
Catenibacterium — +
Cedecea — +
Cetobacterium — +
Citrobacter — +
Clostridium — +
Collinsella — +
Coprobacillus — +
Coprococcus — +
Dorea — +
Dysgonomonas — +
Enterobacter — +
Enterococcus — +
Eubacterium — +
Fusobacterium — +
Hafnia — +
Holdemania — +
Klebsiella — +
Lactobacillus — +
Megamonas — +
Mitsuokella — +
Odoribacter — +
Paenibacillus — +
Parabacteroides — +
Paraprevotella — +
Pediococcus — +
Porphyromonas — +
Prevotella — +
Pseudoflavonifractor — +
Roseburia — +
Ruminococcus — +
Staphylococcus — +
Streptococcus — +
Subdoligranulum — +
Turicibacter — +
Weissella — +
Yokenella — +

I will be adding this information to http://microbiomeprescription.azurewebsites.net analysis underexp

Example:
exa

Additional Literature

  • “Relative abundances of the order Clostridiales and the genus Bacteroideswere directly and inversely related with the ratio estrogen metabolites to estrogen parents, respectively.” [2014]
  • ” However, Methylobacterium radiotolerans was the most significantly enriched and the most prevalent (100% of samples) in tumor tissues, and Sphingomonas yanoikuyae(95% of samples) in paired normal tissues. ” [2014]
  • ” Authors only found higher abundance of Escherichia coli in [cancer] cases compared with healthy controls. [2014]
  • “Absolute numbers of Bifidobacterium and Blautia, and proportion of F Prausnitzii and Blautia were significantly different according to clinical stages [of cancer]. Women with grade III had increased absolute numbers of Blautia sp. compared to women with grade I.
    Significant differences were also found in the absolute numbers of total bacteria and some bacterial groups (F prausnitzii, Firmicutes, Blautia and Egerthella), according to BMI.” [2015]
  • “Relative abundance of several taxa differed between cases and control: case patients had higher levels of Clostridiaceae, Faecalibacterium, and Ruminococcaceae; and lower levels of Dorea and Lachnospiraceae. ” [2015]

We are still in hypothesis land

” In conclusion, links between the microbiome and estrogen-driven breast cancer are growing, and we hope that research will identify specific characteristics of the gut microbiome that can be used to develop novel approaches for breast cancer risk assessment, prevention, and treatment.” [2016]

Bottom Line

The concept of microbiome influencing estrogen and possibly many cancers seems to be growing in popularity with researchers.  The microbiome shifts for different cancers are likely to be different and is a topic that is likely worth returning to in a year when the body of research would be  far greater.

 

Unknown's avatar lassesen 8:30 pm on October 15, 2018  

Antibiotics Resistance Genes

A reader shared their very recent lab results from   GI-MAP DNA Stool Analysis . I found at the bottom of their report something new that I wished was seen on other reports that I have reviewed. The antibiotic resistant genes found in the sample. It appears to have been added in 2018 (2018 Sample Report)

Genes transfer between bacteria, so it is rarely a case of the gene being in one taxonomy only.

“Bacteria can share genes with each other in a process called horizontal gene transfer. This can occur both between bacteria of the same species and between different species and by several different mechanisms, given the right conditions. Gene transfer results in genetic variation in bacteria and is a large problem when it comes to the spread of antibiotic resistance genes…..For example, if a bacterium picks up an antibiotic resistance gene and is subsequently exposed to that antibiotic, this bacterium will be better off than susceptible neighbors and can increase in number.” [Src]

gene1

gene2

A video on this topic.

Bottom Line

Antibiotic resistance is not new. A study on Monks DNA from a 1000 years ago found that the genes were there! [Src] [Summary] – Four monks who lived in the Middle Ages (about 950-1200) and were buried at the monastery of Dalheim, Germany.

“The team found a lot of other interesting things. They also sequenced the genetic material of one of the disease bacteria, T. Forsythia, and found that it has several antibiotic resistance genes.

”This is the first time we see fossil samples from humans with bacteria that have antibiotic resistance – long before we started producing antibiotics industrially,” says Cappellini.

Most antibiotics come from bacteria. Bacteria acquiring resistance to other bacteria is expected in the endless fight between bacteria.

When it comes to dealing with a gut dysfunction, it is likely a good idea to determine what resistance exists in the gut bacteria. A mismatch can easily contribute to further imbalance.

Unknown's avatar lassesen 12:25 pm on October 7, 2018  

Some sources to consider for probiotics

A reader wrote:

I’d like to do:
  • Lactobacillus Fermentum ME3
  • Lactobacillus Kefiri LKF01
  • Lactobacillus Reuteri
  • Lactobacillus Casei
  • Bifidobacterium infantis
  • Bifidobacterium Longum
  • Bifidobacterium bifidum
  • Bifidobacterium Breve
But I don’t find them isolated. 😦
As readers know — I tend to look unfavorably on both probiotics mixtures and probiotics that lacks strain information. If the probiotic source is not human, there is a very low chance that they will take up residency (Soil Based Organism are the probable exception)
The sources that I know of for these are:

Custom Probiotics provide strain information, including the ATCC number.

Note: they may not be available in the country you are in. I have faced that issue often. My past solution is to get an online friend to forward them to you and you buy them and get them delivered to their address, they then forwards as “Gift – probiotics” for customs.

The other option is looking on eBay – the vendors there tend to ignore any government regulations that prevents regular outlets from stocking them or shipping to your location.

Unknown's avatar lassesen 12:01 pm on October 6, 2018  

Reducing the risk of C. difficile while on antibiotics

A reader is dealing with an antibiotic resistant abscess which have kept recurring after several courses of different antibiotics. She wrote because the latest escalation had a risk of  C. difficile. Actually, it is Peptoclostridium difficile  and not Clostridium difficile, because it has been recently reclassified.

The first harsh reality is that 55% of people have some of this bacteria…. so the issue is whether this bacteria will seize the opportunity to expand to clinically significant levels.

  • “Clostridium difficile is the leading infectious cause of antibiotic-associated diarrhea and colitis. C. difficile infection (CDI) places a heavy burden on the healthcare system, with nearly half a million infections yearly and an approximate 20% recurrence risk after successful initial therapy. ” [2018]
  • “Probiotic use did not appear to attenuate the odds of CDI in patients exposed to high-risk antibiotics, but moderate-risk antibiotics appeared to significantly attenuate the odds of CDI in patients who received probiotics.” [2018]
    • “From the perspective of the medical system, oral probiotics as a preventive strategy for CDAD in hospitalized children and adolescents receiving a therapeutic course of antibiotics reduced the risk of CDAD and represents a cost-saving strategy.” [2018]
  • ” C. difficile infection incidence in the United States has increased dramatically since 2000. In the United States ” [2018]
    • “Outbreaks of hypervirulent strains of Clostridium difficile began to be reported in healthcare facilities worldwide around 20 years ago. Concurrently, trehalose became a common additive used by the global food industry. A new study provides evidence that these two observations are a linked phenomenon [2018]

Using the http://microbiomeprescription.azurewebsites.net site, we find that the following reduces this bacteria according to studies:

And the following should be avoided:

Bottom Line

A sugar-free (or at least reducing sugar content) diet is the first suggestion. Increased vitamin B supplementation and melatonin is also suggested. Adding 1-3 bananas a day may also be beneficial as well as making food from scratch (i.e. no prepared foods due to trehalose additives). Evidence for probiotics is generally deemed weak in all of the latest studies.

NOTES:

  • On prepared foods, trehalose may not be explicitly labelled, rather included under “sugar”.
  • Trehalose occurs naturally in small amounts in mushrooms, honey, lobsters, shrimps, certain seaweeds (algae), wine, beer, bread and other foods produced by using baker’s or brewer’s yeast [3].
  • Trehalose is heat stable and preserves the cell structure of foods after heating and freezing, so it is used as a food texturizer and stabilizer in dried foods, frozen foods, nutrition bars, fruit fillings and jams, instant noodles and rice, white chocolate, sugar coating, bakery cream, processed seafood and fruit juices [3,4].