A reader left a comment on probiotic herxheimer reaction page, and wrote:

“The day after a Fecal Microbiota Transplant (FMT) [In Northern Europe] I woke up very constipated, but no other worsening than that. But two days after I became very sick and I just get worse and worse. All my symptoms are worse. A lot of extreme pain, inflammation, neurological symptoms, can’t almost walk etc. I know very well about herx reactions.. I have had a lot of them. …

I just wonder.. Do you think a single (or I’ll do a second one a week after the first one) FMT treatment can produce extreme herx for a really long time if you have a really bad flora as I have? Can it actually last until most of the foe species are gone, if the species from the FMT really has colonized my gut?”

I have an early 2014 post on FMT. My (limited) understanding from reading the literature is that having a herxheimer reaction has been sometimes reported, although usually minor ( cite1). I have located some online journals dealing with more extreme reactions for reference in answering your questions below.

Patient Experience #1

“After the first few transplants I developed die-off… Now I’ve done several cleanses and tried different prescriptions but this die-off did not stop for about 2 weeks straight – It was horrible and severe! So I took a break from the transplants and resumed them several weeks later. The die-off symptoms still remained but became less severe after each transplant. I never did the top-down approach, only bottom up….
After 13 transplants, my donor and I decided to take an extended break for a while and see how things progressed. I could definitely tell a change in consistency and smell. There was definitely less abdominal pain and bloating. However, although I had experienced improvements, my IBS had not been totally eliminated and my CFS symptoms remained.” [cite2]

Patient Experience #2

“Day 2 (after FMT): It’s now Day 2; I ended up holding the solution in all the way through today. The abundance of fiber I ingested yesterday clogged me up a bit, which I do not mind because the longer I can hold it in the longer the bacteria has spread and propagate. I ate an excessive amount of fiber yesterday which normally would make me quite ill; yet it only gave me subtle gas – nothing compared to what it did before. I have not noticed any substantial changes yet however. My diet will be essentially the same as yesterday.

Day 3: Finally went to the restroom at 2 PM today; I had not been able to go since the procedure – this means I held in the solution for 48 hours.The stool was a type 5 on the Bristol stool chart; therefore not in line with healthy stool. I’m not sure whether this is due to die off of the bad bacteria or if it means the procedure does not work, I will have to wait and see. I should know that a heavy amount of fiber is recommended so that the new bacteria can propagate; however if your body is not used to dietary fiber then take it easy the 1st few days or you will constipation yourself – a mistake I made. Today I begin taking Intestinew; a supplement meant to help repair gut lining in order to fix my leaky gut.

Day 4: It’s interesting; I’m actually feeling a bit worse than before I did the procedure. I’m having IBS attacks frequently and my anxiety has risen. I followed the procedure perfectly; so I’m quite dumbfounded on how it could make things worse. Either my problem extends farther than dybiosis or I’m still experiencing die off symptoms; I hope it’s the latter. If anyone has experience with fecal matter transplant die off symptoms please do share what they were. Today I’m continuing with Intestinew and reducing the fiber that I’ve been eating to try to calm the symptoms down.

Day 5: Due to a lack of any results I’m going to discontinue this journal here; I will revisit FMT in about a month and will update my progress then. This specific FMT unfortunately did not yield any results; this may be due to a variety of reasons which will be addressed next time. I still feel FMT is a real means of fixing the bacteria in one’s gut but I can’t say anymore until next month.

[Read the end of this thread, which is page 2, to see what I did following this journal. The FMT’s did work, but it took a much more comprehensive plan.]” [Cite3]

Patient Experience #3

“Once I gave my mom normal functioning bacteria [via FMT], her immune system regained it’s intelligence. She did have severe die off and pain during the FMT’s, but it appears to all have been worth it. Best of luck to all. Search for the best donor! I can even help if you need. Tessnik@yahoo.com” [cite4]

Bottom line

We do not know what the risk(odds) is for a more extreme reaction. We know that it does occur.

• Duration can be expected to be 2-3 weeks. Unlike antibiotics which have a half-life of hours (i.e. the time for half of it to leave the body), organics (bacteria) may not decrease but increase. This applies to both probiotics and fecal transplants.
• Given that this reader is well familiar with herx, it implies that the bacteria that she is fighting likely “explodes” like a suicide bomber when killed, dumping its full load of toxins into the system.

While repeated FMT does work in some, I would suggest considering a slightly different route before the 2nd FMT, namely:

• Myarisan — slowly working up from 1 tablet to normal dosage (18) and then 54 until no herx happens
• Prescript assist — slowly working up to 4x bottle dosage until there is no herx at that dosage
• GeneralBiotics’ Equilibrium — as above

The reasoning is following this idiom”The operation was a success, but the patient died”. Die-off or herxheimer reactions can become life threatening (especially if the MD does not “believe” in them). They can also be exhausting and result in lack of compliance to a treatment plan. If your bacteria produce strong die-off, then you need to move slowly in dislodging them. You want to aim for a state of moderate die off (hopefully with a few hours each day free of it).

Once you have done the above, then try another FMT.

As always, just academic discussion and speculation to discuss with your MD.

In earlier post I cited the mouth as a possible source of bad bacteria repopulating the gut. Taking oral probiotic lozenges and Spezzata candy(pure licorice) , especially if you have dry mouth could help.

On CFS Remission facebook page (feel free to Like it!), a reader asked about using essential oils (neem, tulsi) on the skin and whether it would impact the gut microbiome? My answer was yes, because the microbiome on the skin (anywhere) is touched by the hands which are then brought into direct contact with food (sandwiches, apples, buns, candies) — unless, perhaps, you are very formal Swedes (I was in a MacDonald’s in Stockholm and saw some parents and children eating fries and hamburgers with forks and knives….).

So, your response may be “but I shower everyday!! No way!!!” As always, let us look at what PubMed says…

• “Human skin is the first line of defense against pathogens, while simultaneously harboring a diverse milieu of commensals, including bacteria, fungi, and viruses. These symbiotic organisms play essential roles in lipid metabolism, colonization resistance to transient organisms, and education of the immune system (Belkaid and Segre, 2014; Grice, 2015; Scharschmidt and Fischbach, 2013). “[2016]
• “Despite regular washing and contact with bacteria-laden objects, our personal milieu of skin microbes remains highly stable over time, reports a metagenomics study published May 5 in Cell. The authors say this knowledge could be applied to better understand a wide range of human skin disorders through the development of prebiotic, probiotic, and microbial transplantation approaches.” [2016]

A recent article found that dandruff may result from over abundance of Staphylococcus and undergrowth of  Propionibacterium. People shampoo every day and still have dandruff which appears to confirm that the skin microbes maintain themselves. It also begs the question, do you CFS/FM/IBS sufferers have a higher incidence of dandruff (which has a prevalence of 19% in the general population)?

So fixing the microbiome drags all of the way back to the skin surface! My suggestion to the reader was consider using Neem and Tulsi (and… ) soap as a starting point. These are available on Amazon (search there) as well as Neem and/or Tulsi toothpaste. Rotating to different (true) herbal soaps would also be rational! BEWARE of herbal scented soaps — often they lack the herbs and are made with chemical synthetics.

As always, it may not be needed for some and essential for others.

Issues with cortisol occur in some CFS patients but is not a frequent condition. To me this implies that it is either DNA related or microbiome related.

• Mild hypocortisolism (low cortisol) with attenuated diurnal variation has also been reported in some patients with CFS [2011].
• especially prone in women to support chronically depressed cortisol levels and a persistent inflammatory signature consistent in some CFS populations [2014].
• We concluded that depressed salivary cortisol may be an uncommon factor in CFS as even in those cases where it might play a role it did not persist despite persistence of symptoms [2013].

So which is it — or is it both? The literature indicates that it is influence by stress and has impact on the microbiome.

• Hypocortisolism and increased glucocorticoid sensitivity of pro-Inflammatory cytokine production in Bosnian war refugees with posttraumatic stress disorder[2004].
• Infectious causes of adrenal insufficiency [2003].
• A study with dogs suggest that there is a DNA component “The data supports the existence of breed-specific differences in incidence rates of naturally occurring adrenocortical insufficiency (NOAI) in dogs.”[2016]

“Endocrine pathways such as the hypothalamic-pituitary-adrenal (HPA) axis act as links between the nervous and the immune system via cortisol. In turn, the nervous system is linked to the gut by the vagus nerve as a feedback system for the autonomous gut innervation. In addition, cytokine patterns might play a crucial role in the psychoneuroimmunlogical interplay between gut and brain. These patterns might be altered by cortisol shifts as observed under chronic stress conditions. The immunosuppressive effect of cortisol might also affect the conditions at the gut epithelium as well as gut bacterial composition [2013].”

• Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers[2015]. “The salivary cortisol awakening response was significantly lower after Bimuno®-galactooligosaccharides intake compared with placebo.”
  • “B-GOS consumption led to significant increases in bacteroides and bifidobacteria,” [2015]
  • “B-GOS increased the number of fecal bifidobacteria at the expense of less desirable groups of bacteria”[2013]

Reviewing the literature finds that adaptogens appears to be the herbs of choice for dealing with high cortisol issues. Thus by inference, they should be avoided with low cortisol. This inference may be wrong — their may be normalizer which work on both side of cortisol shifts. For one, Licorice, it doubles the half-life of cortisol (i.e. keep it around longer which implies that it may raise the level).

Wikipedia lists the following:

“There is dispute in the herbal community regarding whether certain plants qualify as adaptogens. However, certain plants are generally believed to qualify:

• American Ginseng (Panax quinquefolius), root^[11]
• Ashwagandha (Withania somnifera), root^[12]
• Asian Ginseng (Panax ginseng), root^[13]
• Cordyceps (Cordyceps sinensis), mushroom/mycelium
• Dang Shen (Codonopsis pilosula, C. tangshen), root
• Eleuthero (Eleutherococcus senticosus), root/stem bark
• Guduchi (Tinospora cordifolia), root/stem
• Holy Basil (Ocimum sanctum, O. gratissimum), herb — aka TULSI
• Jiaogulan (Gynostemma pentaphyllum), herb
• Licorice (Glycyrrhiza glabra, G. uralensis), root
• Reishi (Ganoderma ludicum), mushroom/mycelium
• Rhaponticum (Rhaponticum carthamoides), root
• Rhodiola (Rhodiola rosea), root
• Schisandra (Schisandra chinensis), fruit/seed
• Shilajit (Asphaltum bitumen), pitch ^[14]“

I have high lighted in red the items that I have cited on this blog.

Bottom Line

Traditionally low cortisol was associated with mycobacterium tuberculosis infections, thus the microbiome seen with such patients may hint at the bacteria associated with low cortisol.

• “Phylum-level analysis showed that the relative abundance of Firmicutes and Actinobacteria was significantly higher in TB samples and Neisseria and Veillonella were two dominant genera after Streptococcus.”[2016]
• Aerosol Mycobacterium tuberculosis infection causes rapid loss of diversity in gut microbiota [2014]. [Full Text] Below is a chart showing how bacteria shifted during the course of TB
• 
• Treatment addressing the root cause is largely unknown except that the root cause appears to be largely due to a bacteria shift, a specific subset of bacteria that is not common across CFS patients.

What is really needed is a good study of the microbiome of patients with low cortisol levels. Until then, my best suggestion is: GeneralBiotics Equilibrium, Prescript Assist and Bifidobacteria probiotics.

A reader left a comment on my site this week and asked a few question.

“THANK YOU KEN!!!

I have had great success with your diet/probiotic information and I cannot thank you enough for sharing your story with the world.

I have something that took my health to the next level and I wanted to share it.
Note: This was before I found your blog and had made no other changes to my diet or lifestyle. I have had CFS for 7 years.

For depression, my doctor prescribed Sertraline, a serotonin reuptake inhibitor (SSRI). The first 3 weeks I had a terrible reaction but persevered and after about 12 weeks, I experienced a HUGE reduction in symptoms.

In regards to people with CFS having low E.coli, I have found links between E.coli and Serotonin.
1. “Escherichia coli Nissle 1917 [Mutaflor Probiotics] enhances bioavailability of serotonin in gut tissues through modulation of synthesis and clearance.”http://www.nature.com/articles/srep17324
2. http://www.ncbi.nlm.nih.gov/pubmed/21080162

Maybe low serotonin (low E.coli) resulted in exacerbated pain sensitivity and other symptoms? I believe Sertraline also lowered my stress levels which allowed my immune system to get back on its feet and heal my body.

I also wanted to throw in this little gem about blood type and intestinal microbiota composition, I thought it could be an important piece of information for the overall puzzle.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485159/
I was hoping your PubMed skills could interpret for us? I struggle to understand scientific papers and would love to understand more about this link to our health. My blood type is 0 positive.

Thank you again, Ken! Your work is so appreciated.”

Blood Types

Since blood type is connected to DNA, and your microbiome is connected with your DNA, I am not surprised. I suspect that in time we will find many conditions deemed to be inherited is not inherited by DNA proper, but inherited by microbiome. I include one of the diagrams from the article that you cited. I could not find any studies on fibromyalgia, CFS, IBS and blood types — it would be interesting to see a study on it!

For other microbiome dysfunction associated diseases,

• “[Crohn’s disease] Patients with blood type AB had a better response to Infliximab [IFX] while those with blood type A appeared to have a risk of losing response to IFX.”[2016]
• “Subjects with blood group “B” are at high risk while individuals with blood group “O” are at low peril of evolving type 2 diabetes.” [2016]
• “The frequency of AB blood group was significantly higher in type-1 diabetics; and Ablood group was significantly higher in type-2 diabetics. Furthermore, Rh negativity were significantly more frequent in type-2 diabetics.” [2016]
• ABO histo-blood group might modulate predisposition to Crohn’s disease and affect diseasebehavior.[2014]

Example of how strains varied according to blood type

Serotonin And Probiotics

Many probiotics help with serotonin, they tend to be the same ones that I suggest. “serotonin receptor modulators are used to treat IBS,”[2015]  I did a post on DNA and serotonin earlier this year that may interest some.

• Yakult: “Two weeks after the examination, the Lactobacillus casei strain Shirota (LcS) group had significantly higher faecal serotonin levels (P<0.05) than the placebo group.” [2016]
• Lactobacillus rhamnosus GG supernatant upregulates serotonin transporter expression in intestinal epithelial cells and mice intestinal tissues [2015].
• “L. helveticus NS8 also resulted in lower plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, higher plasma interleukin-10 (IL-10) levels, restored hippocampal serotonin (5-HT) and norepinephrine (NE) levels,” [2015]
• Melatonin production in Escherichia coli by dual expression of serotonin N-acetyltransferase and caffeic acid O-methyltransferase[2016].

Not good:

• “mice treated with either F. prausnitzii strain A2-165 and its culture supernatant (SN) exhibited significant decreases in intestinal permeability, tissue cytokines and serotonin levels.” [2015]

In my last post I learnt about how some bacteria defends themselves against herbal and spices. In this post, I will look at one that is easily available as a supplement Genistein, an isoflavone and antioxidant. There are some risks from high dosages (see wikipedia)

Multidrug pump inhibitors uncover remarkable activity of plant antimicrobials.[2002] “It is possible that the apparent ineffectiveness of plant antimicrobials is largely due to the permeability barrier. ….The results show that the activities of the majority of plant antimicrobials were considerably greater against the gram-positive bacteria Staphylococcus aureus and Bacillus megaterium and that disabling of the MDRs in gram-negative species leads to a striking increase in antimicrobial activity. Thus, the activity of rhein, the principal antimicrobial from rhubarb, was potentiated 100- to 2,000-fold (depending on the bacterial species) by disabling the MDRs.”
[Full Text]

• More on multidrug pump inhibitors: Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations [2014] “Another group of EPIs is called the quinoline derivatives, because of their structural similarity with quinolones [143].”  – interesting because Jadin’s protocol includes the concurrent use of quinolones with other antibiotics.
• “In Gram-positive bacteria, EPIs against the NorA system in S. aureus has been intensively studied. A large number of both synthetic and natural compounds have been found to be EPIs against S. aureus NorA, especially those of natural origins such as genistein isolated from Lupinus argenteus, spinosan A isolated from Dalea spinosa and Tiliroside isolated from Herissantia tiubae”  Genistein is available as a supplement.

So what does PubMed say about it?

• “After 6 and 12 months (of 54mg Genistein daily), our results indicate a strong correlation and a significant effect of genistein in reducing both Hot Flashes and visfatin in women with metabolic syndrome ” [2016]
• “significant reductions in CFUs were found for S. aureus and B. anthracis when cultured in the presence of 100 muM genistein. …However, L. reuteri, E. coli, S. sonnei, and K. pneumoniae were not altered by in vitro culturing in the presence of 100 muM genistein… the use of genistein in combination with probiotics may augment the effectiveness of antimicrobial therapies currently used in the management of infections” [2006]
• Genistein inhibits pro‑inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway.[2014] “Genistein significantly decreased IL-6 and IL-1β mRNA levels, as well as IL-6 production in PMA/A23187-induced mast cells activation. In addition, genistein inhibited the phosphorylation of ERK 1/2 in PMA/A23187-induced mast cell activation. However, phosphorylation of p38 was not altered. Thus, these findings indicate that genistein inhibited the inflammatory status of mast cells through inhibition of the ERK pathway.”

Bottom Line

There is a lot of articles on this, my main take away is that it appears to have no impact on families that are undergrowths in CFS and does impact overgrowth. It should help with mast-cell/histamine issues (for that subset), and may have additional benefits.

More research is needed, but this looks like a very promising supplement.