A Facebook reader posted:

“I’m wondering your thoughts on Turmeric/Curcumin in relation to the current model. I’ve searched your site and found a few older posts about its benefits, but noticed it wasn’t included in your herbal antibiotic chart. Curcumin helps me a lot with pain and since I’m in a fibro-flare right now, I’m back on it multiple times per day. But it seems to make me more and more tired the longer I take it. This is a clear pattern, probably the 10th time I’ve taken it for pain. My thought was maybe it has a negative impact on e.coli or Lactobacillus or some other species I might be low in. I couldn’t find anything specific on PubMed.”

Rotate, Rotate, Rotate

If something is anti-infection, you need to rotate the use of it. Say that it is 95% effective against a specific family, that means 5% of a bacteria family can resist it.  When the 95% dies, the remaining 5% will slowly grow to take it place.  Curcumin or whatever — will no longer be effective against that family because your eventual population will likely be 95% resistant. The bacteria quickly learns that the genes for resistance (although expensive to keep going) is preferred.

There are several studies that found that pulsing antibiotics was more effective than continuous application. Bacteria are adaptive, not machines.

Research Update on Curcumin

Image from http://www.hindawi.com/journals/bmri/2014/186864/

• showed a marked inhibition of the growth of Staph. aureus. [1949]
• extended antimicrobial activity of curcumin and safety property even at high doses (12 g/day) assessed by clinical trials in human [2014]
  • …with 45% and 30% inhibition rates against Staphylococcus aureus and Escherichia coli
  • demonstrated the MIC (minimum inhibitory concentration) …. against
    • S. epidermis ATCC 12228,
    • Staph. aureus ATCC 25923,
    • Klebsiella pneumoniae ATCC 10031, and
    • E. coli ATCC 25922 [15].
  • antibacterial effect against 13 bacteria, namely,
    • Vibrio harveyi,
    • V. alginolyticus,
    • V. vulnificus,
    • V. parahaemolyticus,
    • V. cholerae,
    • Bacillus subtilis,
    • B. cereus,
    • Aeromonas hydrophila,
    • Streptococcus agalactiae,
    • Staph. aureus,
    • Staph. intermedius,
    • Staph. epidermidis, and
    • Edwardsiella tarda.
  • Turmeric oil as a byproduct from curcumin manufacture also was found effective against
    • B. subtilis,
    • B. coagulans,
    • B. cereus,
    • Staph. aureus,
    • E. coli, and
    • P. aeruginosa [19].
  • showed significant antibacterial activity …against 65 clinical isolates of Helicobacter pylori [41].
  • It has been demonstrated that curcumin as a plant derivative has a wide range of antiviral activity against different viruses…including parainfluenza virus type 3 (PIV-3), feline infectious peritonitis virus (FIPV), vesicular stomatitis virus (VSV), herpes simplex virus (HSV), flock house virus (FHV), and respiratory syncytial virus (RSV)
  • The methanol extract of turmeric demonstrated antifungal activity against Cryptococcus neoformans and Candida albicans with MIC values of 128 and 256 μg/mL, respectively [16].
  • Study of curcumin against 14 strains of Candida including 4 ATCC strains and 10 clinical isolates showed that curcumin is a potent fungicide compound against Candida species
  • S. mutans and L. acidophilus were susceptible to curcumin in the presence of blue light.[2014]

Bottle Line

The reader is correct that “My thought was maybe it has a negative impact on e.coli or Lactobacillus”. Taking it knocks down the symptom causing bacteria but to take it continuously runs multiple risks:

• Resistance being developed by the symptom causing bacteria
• Reduction of good bacteria that was already low….

Via facebook, I shared a link to a survey on the 10 best candidate probiotics for ME/CFS/IBS. I expect the response to vary from person to person. An example is below in an email thread from a reader. There is no magic formula, just experiments with better than average odds that are worth trying:

Reader:

” I’ve had a terrible couple of weeks herxing on Miyarisan and Symbioflor 2, plus everyone has had a terrible head cold…
I think I might have a coagulation issue after taking too much Symbioflor 2, I have a puffy face in the morning, mental fog, very thirsty, bruising easily, very tired and I feel cold in my hands and feet – does that sound like it might be? I’ve stopped all probiotics but wasn’t sure what I should do next. Fibrinolytics? Antibiotic herbs? I am too foggy to read about it. 
The worst part is, when I came off Miyarisan I was feeling on top of the world and now I’m back in the dumps again!! “

Ken:

• Switch back to miyarisan ASAP. You are the third person to indicate feeling bad from Symbioflor-2.

Reader:

• “Within 24 hours back on Miyarisan, my swelling went down, energy returned and the fog lifted. Thanks for the tip. I feel great again. I can get used to this! :)”

Note on the why of the above suggestion, Miyarisan suppresses E.Coli, hence should not be taken together. If a E.Coli probiotic takes up residence and producing too much herx — then Miyarisan (or general Lactobacillus probiotics) will suppress the E.Coli/

Survey Results

Also see Herb Results

The number of responses is low to use reliably. I am posting them to encourage others to do the survey. The best odds from this data is (in descending order – NO REPORTED NEGATIVE IMPACTS)

• GB Equilibrium (No negative effect, 100% saw improvement),
• L. Plantarum 229V (50% improved)
• L.Reuteri (50% improved),
• Align (46% improved),
• Culturelle (40% improved)

Some negative risk but good improvement profile

• Miyarisan (36% odds of having issues, if no issue – 55% chance of improving!)
• Mutaflor (22% odds of having issues, if no issue – 67% chance of improving!)
• Symbioflor-2 (27% odds of having issues, if no issue – 55% chance of improving!)

Go to survey and then be shown the results.

As of Nov 23,2016

Recently I came across a PubMed article on iron deficiency with inflammatory bowel disease (IBD) which found “Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy…. Both per oral (PO) and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV…. PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. ” [2016]

The superiority of IV over Oral  with IBD is cited in other articles:

• “Intravenous iron treatment is better tolerated and more effective than oral iron treatment in improving ferritin.” [2012]
• “Patients who received IV iron had a greater rise in serum ferritin and were less likely to stop treatment due to adverse events, when compared with those who received PO iron.” [2015]

Iron and CFS

This appears to impact a subset of CFS patients.

• “The results indicate that  [CFS] patients had significantly increased serum aluminum and decreased iron compared to controls. In the females, serum iron and dehydroepiandrosterone sulphate were significantly decreased and correlated.” [2001]
• “We reviewed, in this study, symptoms and syndromes associated with iron deficiency with or without anemia: fatigue, cognitive functions, restless legs syndrome, hair loss, and chronic heart failure. Iron is absorbed through the digestive tract. …Pathogenic micro-organisms or intestinal dysbiosis are suspected to influence iron absorption.” [2014]
• Iron insufficiency and hypovitaminosis D in adolescents with chronic fatigue and orthostatic intolerance [2011].
• “Although the cause of primary Restless legs syndrome (RLS) is still unknown, there is a strong connection between central metabolism of iron as well as dopamine levels and RLS manifestation.” [2011]

Probiotics and Iron

A quick summary is in “Gut microbes may play key role in iron status”

• Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age[ 2015 ].
• The microbiota shifts the iron sensing of intestinal cells [2016]. “The amount of iron in the diet directly influences the composition of the microbiota. Inversely, the effects of the microbiota on iron homeostasis have been little studied….Commensal organisms (Bacteroides thetaiotaomicron VPI-5482 and Faecalibacterium prausnitzii A2-165) and a probiotic strain (Streptococcus thermophilus LMD-9) led to up to 12-fold induction of ferritin in colon.”
• “No significant differences were found between the two yogurts (one with live  cultures and the other without) in terms of their effects on serum iron, AST and ALT levels.” [2013] – so only certain  bacteria are involved.
• Probiotic bacteria reduce salmonella typhimurium intestinal colonization by competing for iron [2013]. “Thus, iron availability impacts S. Typhimurium growth, and E. coli Nissle reduces S. Typhimurium intestinal colonization by competing for this limiting nutrient.” – So E.Coli probiotics and iron deficiency may not play well together.
  • ” Intestinal bacteria compete for the essential nutrient iron, leading to replacement of pathogenic Salmonella by the probiotic Escherichia coli Nissle, which is better equipped with iron acquisition systems, and resolution of infectious colitis.” [2013]
• Probiotics Lactobacillus reuteri DSM 17938 and Lactobacillus casei CRL 431 modestly increase growth, but not iron and zinc status, among Indonesian children aged 1-6 years [2013].
• Oral administration of Bifidobacterium longum CECT 7347 ameliorates gliadin-induced alterations in liver iron mobilisation [2013].
• “Bifidobacterium bifidum.. decreased amounts of calcium and iron released from bread.” [2012]
• “we show that a panel of probiotics are not able to respond to increased iron availability, and identify an isolate of Streptococcus thermophilus NCIMB 41856 that can increase growth rate in response to increased iron availability.” [2011]
  • “Species of lactic acid bacteria that have been employed as probiotics were used. These were: L. bulgaricusJB005, L. casei JB006, L. casei JB008, B. animalis JB007, and B. bifidum JB009 (isolated from yoghurt); L. plantarum JB012 and L. helveticus JB012 (isolated from probiotic capsules); and the commensal isolates L. acidophilus ASF360 and L. salivarius ASF361 (components of the Schaedler flora). Two strains of S. thermophilus (JB004 and NCIMB 41856) were isolated from yoghurt. Two strains of AIEC were used: HM427 and HM615 (kindly provided by Dr Barry Campbell and Prof Jon Rhodes, University of Liverpool), as was E. coli K12 and E. coli Nissle 1917 (isolated from Mutaflor (Ardeypharm GmbH, Herdecke, Germany)).”

Bacteria and Iron

I have heard people express the opinion that some bacteria, like Lyme, need iron, that you should avoid iron supplements. To me this is a gross and perhaps, dangerous simplification. It is like saying, “Mafia are Italians, so to solve the Mafia problem, we need to deport all of the Italians” (or Japanese, or Muslims, or…).

“A Syracuse University research team… discovered that some bacteria are equipped with a gene that enables them to harvest iron from their environment or human host in a unique and energy efficient manner.”[2008] Thus an overgrowth of Actinomycetes may result in iron deficiency.

Below is a table from [2006], some strains are good and other are bad. “Macrophages use iron for production of hydroxy-radical and superoxide reactions, which are necessary for microbial killing. Presumably, as a survival strategy, bacteria, which also require iron for survival, have adapted the ability to sequester iron from the host, thereby limiting the availability to macrophages.” [2007]

Bottom Line

First thing is that you cannot deal with all issues at the same time. You must choose which one you will direct your efforts towards improving. The gut bacteria dysfunction was a cascade of changes, and unwinding it means addressing one issue at a time. Where to start? There is no literature indicating the fulcrum that should be our start point — so my suggestion is simple: the very worst symtpom!!

If you have low iron and thus tiredness, low hemoglobin (and thus oxygen), insomnia, etc, you may wish to try to address that first. From the literature above, besides eating iron rich food, you should take, if available:

• Streptococcus thermophilus NCIMB 41856 [Patent] – may be available soon
• Lactobacillus plantarum 299v – Jarrow brand, available on Amazon, and in Sweden as “ProViva Naturell Filmjölk”
• Bacteroides thetaiotaomicron VPI-5482
• Faecalibacterium prausnitzii A2-165
• Streptococcus thermophilus LMD-9

Streptococcus thermophilus is in most yogurts (see Probiotic Yogurt for a list, for example Chobani contains none), the problem is usually which strain is used!

You should also consider taking IV Iron, it improves the gut bacteria more than oral iron. In general, “The present results suggest that Fe[Iron] supplementation enhances the concentration of beneficial gut microbiota metabolites and thus may contribute to gut health.” [2014]

Note that all of these are specific strains. Streptococcus thermophilus JB004 did not show strong effects.

You should also avoid Mutaflor, Symbioflor-2, Bifidobacterium bifidum which will decrease iron availability.

At Costco today, I noticed a product and checking the label I found that it was a single strain. A quick check on PubMed, found enough interesting items to toss one in the cart.

My usual reaction to seeing ‘probiotic gummies’ is to dismiss it as marketing…

• Bacillus coagulans GBI-30, 6086 Modulates Faecalibacterium prausnitzii in Older Men and Women 2015]. “Consumption of BC30 significantly increased populations of Faecalibacterium prausnitzii by 0.1 log10 cells/mL more than during consumption of the placebo (P = 0.03), whereas populations of Bacillus spp. increased significantly by 0.5 log10 cells/mL from baseline in volunteers who consumed BC30 (P = 0.007)” which has cascading impacts:
  • “Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn‘s disease[2016].
• Effect of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation ofBacillus coagulans GBI-30, 6086.
• “Baseline populations of Faecalibacterium prausnitzii, Clostridium lituseburense,Eubacterium rectale and Bacillus spp. were significantly higher in those having consumed BC30 compared to the placebo.” [2014]
• ” possible benefit of this probiotic for residual inflammation in treated HIV-1 infection, although further study will be required to determine the immune pathways involved.” [2014]
• Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice [2012].
  • Bacillus Coagulans GBI-30 (BC30) improves indices of Clostridium difficile-Induced colitis in mice[2011].
• Use of a continuous culture fermentation system to investigate the effect of GanedenBC30 (Bacilluscoagulans GBI-30, 6086) supplementation on pathogen survival in the human gut microbiota. “suggesting that a bi-modal lifecycle of GanedenBC(30)in vivo may lead to anti-microbial activity in distal regions of the gastrointestinal tract.”
• Effects of a proprietary Bacillus coagulans preparation on symptoms of diarrhea-predominant irritable bowel syndrome [2009]. “Of the remaining 52 patients with IBS-D, the average number of bowel movements per day was significantly reduced for patients treated with B. coagulans GBI-30, 6086”
• Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial[2010]. “Compared with placebo, Bacillus coagulans GBI-30, 6086 treatment resulted in greater improvement in patient global assessment and self-assessed disability; reduction in CRP; as well as the ability to walk 2 miles, reach, and participate in daily activities.”
• Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS[2009].
• A patented strain of Bacillus coagulans increased immune response to viral challenge [2009].

Bottom Line

Give me gummies! This was a totally unexpected find.

WARNING: This is a histamine producer. See this post on bacillus and histamines. It is not suitable for all CFS patients.

P.S.  Schiff also sells it in capsules — but taking Gummies is much more fun!

This week  there was a new study published “Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.” Jun 23, 2016. [Full Text]

“We observed that bacterial diversity was decreased in the ME/CFS specimens compared to controls, in particular, a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum. In the patient cohort, we find less diversity as well as increases in specific species often reported to be pro-inflammatory species and reduction in species frequently described as anti-inflammatory. Using a machine learning approach trained on the data obtained from 16S rRNA and inflammatory markers, individuals were classified correctly as ME/CFS with a cross-validation accuracy of 82.93 %.”

• “Both found that D-lactic acid-producing Enterococcus andStreptococcus species were strongly over-represented in ME/CFS patients and that among anaerobic bacteria, Prevotella was a bacterial genus found to be in excess in subjects with ME/CFS.”

Of course, the reader will likely ask – What are the Firmicutes? Check out Wikipedia or see image below.

Of course, 18 years ago this was reported in Australia at the 1998 Alison Hunter Memorial Clinical and Scientific Meeting. “For the anaerobes, the mean percentage distribution of Bacteroides spp. for the control subjects and CFS patients was 92.8% and 91% respectively; Bifidobacterium spp, 7.1% and 2%; Lactobacillus spp., < 1% and 0%.”

In 2009 Sheedy, reported the overgrowth of d-lactic producing bacteria in CFS/ME patients and states ” Given the fact that this might explain not only neurocognitive dysfunction in CFS patients but also mitochondrial dysfunction, these findings may have important clinical implications.” That is two major set of symptoms come from the bacteria shift.

In 2013, by Kenny De Meirleir “A highly significant separation could be achieved between Norwegian controls and Norwegian patients: patients presented increased proportions of Lactonifactor and Alistipes, as well as a decrease in several Firmicutes populations”

As well as difference seen with exercise reported in 2015, ” Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls.”

• “Of note is the significant increase in the relative abundance of Bacilli in blood samples collected from ME/CFS patients at the 48 hour time point. We also observed rapid changes in the relative abundances of the Clostridium XIVa and IV clusters, belonging to the phylum Firmicutes, in blood samples collected 15 min after maximal exercise from ME/CFS patients, but not healthy controls (Fig 3).”

The Awkaward Questions for Physicians and Researchers

With this information being known for 18 years and multiple specialized probiotics being effective for IBS (see this post for the literature), why are there no published studies on the use of the IBS successful probiotics on CFS/ME?

My model is in 100% agreement with this study,  this site attempts to read the literature, find good candidate probiotics, herbs and even antibiotics and suggest them. They worked for me and have worked for a number of readers – especially one that was almost wheel chair bound in Spain a year ago — who just messaged me that she spent the entire day cleaning the house — spotless. Her 3rd day of working all day long without payback.

There was another study (not CFS/ME) that found 93% accuracy for multiple conditions from microbiome samples… a k a stool samples.