I periodically review news releases on probiotics. For example Sjögren Syndrome has a distinctive shift of bacteria. There is a lot of research going on and knowledge increases often.

Bacteria that make brain chemicals[article]

Source: T.G. Dinan et al/J. Psych. Res. 2015

• Altered Mucosal Microbiome Diversity and Disease Severity in Sjögren Syndrome..Stool from SS subjects had greater relative abundances of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, andStreptococcus, while relative abundance of Bacteroides, Parabacteroides,Faecalibacterium, and Prevotella was reduced compared to controls. The severity of SS ocular and systemic disease was inversely correlated with microbial diversity. These findings suggest that SS is marked by a dysbiotic intestinal microbiome driven by low relative abundance of commensal bacteria and high relative abundance of potentially pathogenic genera that is associated with worse ocular mucosal disease in a mouse model of SS and in SS patients.” [article]. This often is co-morbid to CFS/FM.
• “antibiotic-induced gut microbiota disturbance can impair novel object recognition in mice.” [2016] “Antibiotic treatment strongly disrupted and diminished the microbial community in the colon of antibiotic-treated mice. Also, microbial metabolite levels were markedly decreased in the colonic luminal contents of antibiotic-treated mice. Particularly, the colonic levels of the short-chain fatty acids acetate, butyrate and propionate as well as of trimethylamine, adenine and uracil were significantly diminished by antibiotic treatment.Circulating metabolite levels were also markedly altered by antibiotic treatment.”
• “a team led by researchers at Shanghai Jiao Tong University, China, have found that the severity of dandruff is linked to the composition of those microbes-in particular, bacteria-offering potential opportunities for treatment.” [2016]
• “The Spanish firm Biosearch Life has filed for a health claim linking a probiotic strain with the reduced risk of painful inflammation of the breast during breastfeeding.”[2016]
• “MESSAGE RECEIVED A microbe called Bacteroides fragilis (left image, boxed) sends out messages that calm the immune system, quelling inflammation in mouse intestinal cells (left, bottom half). These messages rest in pouches called outer membrane vesicles (yellow bubbles in reconstruction of microbe at right). Defective genes linked to Crohn’s disease might make it hard for people to get such messages.”[2016]
• “Autoimmune disease in children could be caused by gut bacteria that inhibit immune development. Surface lipopolysaccharide (LPS) is made by microbes such as Escherichia coli and helps immune cells to mature.” [2016]
• “Heat-killed Pediococcus pentosaceus LP28 derived from the longan fruit may help trim waist lines and reduce body fat, say results from a double-blind, randomized, placebo-controlled study.” [2016]
• “Researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and their colleagues sequenced the DNA of bacterial strains in patients with metabolic syndrome who each received an FMT, finding that donor strains persisted in the recipients’ guts for up to three months following the procedure…
  Bork also noted that new strains of bacteria transferred more easily than new species….Rather, the success of the transplant appears to depend on the compatibility between the donor and the recipient.
  ” [2016] – FMT does not make a permanent change, it gives an opportunity for normalization; this may be why FMT does not work always for CFS.
• “The United States Food and Drug Administration’s (FDA) regulation of products containing probiotics is complex and largely depends on the claims that are made for the product. For example, they can be regulated as foods, dietary supplements, cosmetics, or drugs/biologics. This article is the first of a four part series about the regulation of probiotics in the USA, and we start with foods.” [article]
• “Intestinal bacteria play a key role in causing and preventing obesity and neurodegeneration and a study has suggested they could also reduce cancer risk.” [article]
• Mouth Bacteria
  • “The mix of bacteria living in the oral cavity is related to a person’s risk of developing pancreatic cancer, according to a study…”We found that Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, two species of bacteria linked to periodontal disease, were associated with a more than 50 percent increased risk of pancreatic cancer,” [Apr 2016] I suspect this may also apply to FM and CFS!
  • “In the journal Medicine comparing patients on dialysis who received periodontal treatment with those who did not. Those getting treatment had an almost 30 percent lower risk of pneumonia and hospitalization from infections. Another study published earlier this year found that gum disease is associated with a roughly 10 percent higher mortality over 10 years among patients with kidney problems…Cognitive decline among Alzheimer’s patients with gum disease versus those with healthy gums 2.5 times greater” [article]
  • “One study concluded that L.Reuteri reduced both gingivitis and plaque in patients with moderate to severe gingivits in 14 days. …in another study no significant difference [article]
• “Unexpected phage-bacteria interactions in a simplified murine gut environment Lately gut microbiota scientists have been paying more attention to phages-bacterial viruses-in the gut environment, to uncover how they interact with bacteria to affect activities in the gut.”[article]

I noticed today on facebook that someone posted a link to a NewScientist article Antibody wipeout found to relieve chronic fatigue syndrome (1 July 2015) dealing with the use of Rituximab. This is an anti-cancer drug. Since 2002, I have personally met physically several CFSers that went into full remission of CFS after treatment for cancer. The results are very believable that  “Eleven of the 18 responders were still in remission three years after beginning the treatment, and some have now had no symptoms for five years”.

I know that cancer treatment results in a massive change of the microbiome (exactly what my model asks for!). For example:

• Chemotherapy-driven dysbiosis in the intestinal microbiome[2015]. “We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes (P = 0.0002) and Actinobacteria (P = 0.002) and significant increases in abundances of Proteobacteria (P = 0.0002) compared to samples collected before chemotherapy.”
• Effect of chemotherapy on the microbiota and metabolome of human milk, a case report[2014]. “Chemotherapy caused a significant deviation from a healthy microbial and metabolomic profile, with depletion of genera Bifidobacterium, Eubacterium, Staphylococcus and Cloacibacterium in favor of Acinetobacter, Xanthomonadaceae and Stenotrophomonas.”
• 16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation[2014]. ” Chemotherapy was associated with a drastic drop in Faecalibacterium and accompanied by an increase of Escherichia.”
• Oral microbiota distinguishes acute lymphoblastic leukemia pediatric hosts from healthy populations [2014]. “patients who developed subsequent bacteremia, or bloodstream infection exhibited decreased overall diversity and decreased abundance of taxa including Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella. Using machine-learning methods, we developed a BSI risk index capable of predicting BSI incidence with a sensitivity of 90 % at a specificity of 90 % based only on the pretreatment fecal microbiome.”
• Fecal microbiota diversity in survivors of adolescent/young adult Hodgkin lymphoma: a study of twins [2013]. “Adolescent/young adult Hodgkin lymphoma survivors appear to have a deficit of rare gut microbes.”
• Also, very intersting: Lymphoma caused by intestinal microbiota[2014]. “While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.”

So, we have Staphylococcus decrease and Escherichia increase – which is precisely the type of shift that I have been advocating….

What does PubMed say for CFS?

There are just 12 studies at the moment, newspaper reports tend to often tilt results to sell newspaper.

• “Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms.” [2016]
• “In a subgroup of ME/CFS patients, prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses.” [2015]
• “The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses.” [2011]

Bottom Line

We have a drug that causes remission in a subset of CFS patients [Fact]. The drug causes multiple effects: B-lymphocyte depletion and shift of the microbiome. Which effect (or a third unknown one) is the cause of remission?

IMHO the shift of the microbiome is more likely, many people have reported on this site (and by private email), significant improvement of symptoms by shifting the microbiome by just probiotics and supplements. There is no apparent link to B-lymphocyte with that treatment.

The model also predicts that any treatment will only be effective on subsets because the success is determined by the effectiveness of the treatment against the very specific strains that a person has. This is what is reported in the above literature — effective for a subset.

If you can get this prescribed by your MD, covered by insurance, and you fully understand the risks (see official literature), then give it a try. For myself, I would exhaust the appropriate probiotics and appropriate antibiotic paths first.

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.