Overall cholesterol has been reported normal with CFS, but HDL (the good cholesterol) is significantly low. This can result in MDs doing symptom/lab results treatment instead of addressing the root cause.

• “Plasma lathosterol was decreased in both males and females with CFS (Tables 2 and and3).3). Total plasma cholesterol, desmosterol, cortisol, and aldosterone were normal in both males and females with CFS….Our data are consistent with increased flux through the desmosterol pathway to maintain normal cellular levels of cholesterol. The desmosterol pathway corresponds to the stress-inducible arm of de novo cholesterol and sterol synthesis.” [2016] While total cholesterol was normal, the mechanism of production was not.
  • “Plasma chenodeoxycholic acid (CDCA) was decreased in females (Table 3, Females). CDCA is a primary bile acid made from cholesterol. Decreased cholesterol flux can result in decreased substrate for bile acid synthesis needed for normal fat digestion and microbiome signaling (24). The absence of adequate bile acid delivery can lead to a loss in intestinal mucosal integrity and leaky gut via a cascade of events stemming in part from disrupted farnesoid X receptor signaling”
  • “These facts suggest that CFS is an evolutionarily conserved, genetically regulated, hypometabolic state similar to dauer that permits survival and persistence under conditions of environmental stress but at the cost of severely curtailed function and quality of life.” – except the stress in this case is caused by bacteria shifts.
• “The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (the good cholesterol) (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol...The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. ” [2012]
• “a control group of 40 healthy women and 40 CFS women. Levels of total cholesterol (TC), triglycerides (TG), LDL cholesterol (LDLc), HDL cholesterol (HDLc), and malondialdehyde (MDA) levels were measured. There was a negative correlation between HDLc and MDA levels (r=0.3; P=.046), a positive correlation between TG and MDA levels (r=0.4; P=.006), and lower levels of HDL cholesterol in the CFS group (P=.036). [2010]
• “Bacteroidetes showed positive correlation with LDL- and HDL-cholesterol levels, whereas Firmicutes showed negative correlation with total cholesterol, LDL- and HDL– cholesterol.” [2016]

Concurrent Treatment

Or should I say, how to help correct the shift of bacteria and improve HDL cholesterol. There were sufficient human studies to just use those.

“Recent population-based association studies have shown that the gut microbiota composition can explain a substantial proportion of the inter-individual variation in blood triglycerides and HDL-cholesterol level and predict metabolic response to diet and drug.” [2016]

• Almond Oil – “almond oil elevating the levels of so-called ‘good cholesterol’, high-density lipoproteins (HDL), whilst it reduces low-density lipoproteins (LDL).” [2010] I suspect eating almonds may be as good or better.
  • ” replaced half of their habitual fat (approximately 14% of approximately 29% energy) with either whole almonds (WA) or almond oil (AO) for 6-wk periods… whereas HDL cholesterol increased 6%.” [2002]
• The use of probiotic L. fermentum ME-3 containing Reg’Activ Cholesterol supplement for 4 weeks has a positive influence on blood lipoprotein profiles and inflammatory cytokines: an open-label preliminary study[2016]. “HDL cholesterol level rose from 1.60 to 1.67 mml/l,”  i.e. 4%.
• “a probiotic containing… L. Casei, B.Bifiudu and L. Fermentum .. significantly increased HDL-cholesterol levels (2.7 from 0.9 ) compared with the placebo after 12 weeks.”  [2016] – a 200% increase in HDL.
• “Previous clinical studies have reported mixed results regarding the effect of probiotics on lipid metabolism…Subjects treated with probiotics demonstrated reduced total cholesterol and LDL cholesterol compared to control subjects by 7.8 mg/dL (95% CI: -10.4, -5.2) and 7.3 mg/dL (95% CI: -10.1, -4.4), respectively. There was no significant effect of probiotics on HDL cholesterol or triglycerides.” [2015] L. Fermentum appears not to be included in this review.

The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids [2015].

• “we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤ 25.9% of high-density lipoprotein (HDL) variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol.”

“Akkermansia , Christensenellaceae (phylum Firmicutes; N¹⁸) and the phylum Tenericutes and higher levels of HDL (P=0.0047 and P=0.0006, respectively) [RED in chart above]… genus Eggerthella (N³) with  decreased HDL (P=6.3×10⁻⁵), [BLUE in chart above]”

“We observed that the gut microbiome makes a significant contribution, beyond that of clinical risk factors and genetics, to the individual variance seen in BMI and to the blood levels of triglycerides and HDL,but that it has little effect on LDL or TC levels. ”

Bottom Line

While the bacteria cited above are not currently available as a probiotics, we do have L. Fermentum available as a probiotic that has significant effect after 4 weeks and major effect after 12 weeks. Adding almonds as a regular part of your diet would also help.

In my last post, we found that probiotics may last for just hours or months – depending on the sourcing and type of bacteria. Probiotic behaviors vary greatly. Some produce natural antibiotics that will kill off other species. Others do not — just reduce inflammation etc. or grow more aggressively than bad bacteria. Some commercial probiotics are documented in FDA filing to be easily killed by almost all antibiotics, not to persist and not to produce toxins against other bacteria (good or bad).

We have limited knowledge of which ones produces natural antibiotics, so my rule of thumb is that probiotics should be viewed as producing antibiotics. You should rotate them regularly to prevent resistance to their natural antibiotics occurring. The same applies to herbs. Changing providers when you finish a herb is similarly desired.

The lack of (successful) studies on fixing dysfunctional microbiome

My model appears to be well supported by  Kyberkompact lab results, published papers over seventeen (17) years, etc.

• ” In contrast, in the stool samples there was a higher relative abundance of Bacteroidetes and lower abundance of Firmicutes observed in ME/CFS patients compared to healthy controls.” [2015]
• ” 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%. The incidence of CFS patients with faecal E.coli greater than the percentage mean of control subjects was significantly different to that of the Bacteroides spp. (7 vs 21 respectively, p=0.0001) suggesting the possibility of an antimicrobial interaction among bacterial species.” [1998]

What is lacking are studies showing consistent successful treatment that persists.

• “The high success rate and safety in the short term reported for recurrent Clostridium difficile infection has elevated Fecal microbiota transplantation (FMT) as an emerging treatment for a wide range of disorders, including Parkinson’s disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism.” [2016]
  • I have corresponded with several people that had them, went into remission for months and then relapses
• “Case reports of FMT have also shown favorable outcomes in Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.” [2015]
• “This raises the question of whether restoration of a healthy microbiome via probiotics or other ‘dysbiosis therapies’ would be an optimal alternative, or parallel treatment option, to antibiotics.” [2016]
• “The use of specific probiotics in patients with IBD can be recommended only in special clinical situations. There is no evidence for efficacy of probiotics in CD. By contrast, studies in UC have shown a beneficial effect in selected patients.” [2016]

My approach

The use of antibiotics must be divided into two groups:

• Acute infection treatment – typically resolved by a single course of antibiotics over 2 weeks with a focus on a single bacteria.
• Latent/chronic/persistent/occult infections – which are complex to treat.

It is the latter that is needed for CFS, FM and many autoimmune diseases. We are not trying to eliminate one bacteria but reduce dozens of families while increasing dozens of families. When some of the counts for families are reduced to 1% of normal or even 1% of 1% (1/10000), getting those counts up is a challenge, a 400% increase of some counts do not even touch the dysfunction.

We do not know the complete complex interactions between strains, species and families of bacteria. We try to change one item and the side-effects may leave the patient worst.

How to proceed?

My approach comes from being placed successfully into remission three times using rotating antibiotics. The first time, before CFS was a clinical diagnosis (in 1972-3, Incline Village was in 1984) and the physician went with the diagnosis of antibiotic resistant walking pneumonia – rotating antibiotics when one course did not resolve it. The latter two times, modelling treatment on Dr. Cecile Jadin’s protocol for occult rickettesia infections (although my medical records for the last time read chronic lyme).

Bacteria mutate and become resistant. You may eliminate 99%, but if the environment supports growth, that 1% grows quickly and the volume returns. Our goal is to reduce parts of this consortium of evil bacteria until the good bacteria can muscle back in. Each herb, probiotic or antibiotic will only influence a few families of bacteria. You can knock those back and then reduce their friends, and then their friend’s friends.

There is a little literature on rotation:

• “This review provides an overview of… antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.” [2015]
• “Furthermore, improvements in clinical practice, rotation of antibiotics, herbal drugs, nanoantibiotics and the development of newer antibiotics based on a pharmacogenomic approach may prove helpful to overcome dreadful vancomycin-resistant enterococcal infections.” [2014]
• Antibiotic rotation strategies to reduce antimicrobial resistance in Gram-negative bacteria in European intensive care units: study protocol for a cluster-randomized crossover controlled trial [2014]
• Implementation of antibiotic rotation protocol improves antibiotic susceptibility profile in a surgical intensive care unit. [2007]
• “A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01).” [2013] – A 90% drop in episodes
• Rotating antibiotics selects optimally against antibiotic resistance, in theory[2010.

Pulsing

Pulsing is much less studied. If you rotate, you are in one sense pulsing. Again, very little literature because for most infections – a single course of antibiotics is sufficient to knock out one bacteria.

“The issue of whether it is better to administer antibiotics as an intermittent bolus dose or a continuous intravenous infusion has been debated for several decades.” [1988]

• My own experience has been modeled on Jadin’s protocols (See this summary)
• “While this study does not demonstrate a superior response to dosing metronidazole in a pulsatile fashion against B. fragilis and B. thetaiotaomicron isolates, the effect is comparable to that of conventional dosing regimens. Perhaps this novel dosing strategy would prove advantageous against other pathogens.” [2004] – no worst than taking it constantly etc.
• “In the current study, use of pulsatile dosing against S. pneumoniae with reduced susceptibility demonstrates superior reduction in bacterial concentration compared to that of more traditional two- or three-times-daily dosing. However, further research exploring the mechanism for pulsatile dosing and confirmation of these results are needed before applying this information clinically.” [2006]
• “Overall bacterial density reduction was similar between the regimens for the susceptible isolate and greater with pulsatile regimens against the less susceptible strain.” [2004] – pulsing works better when the bacteria is more resistant.
• A 2012 mathematical modeling study pulsing may be the preferred application of anti-pathogens: “We find that constant dosing is not the optimal method for disinfection. Rather, cycling between application and withdrawal of the antibiotic yields the fastest killing of the bacteria.”

Bottom Line

I advocate rotation and/or pulsing. See earlier post from 2015. The key for knowledgable medical professional to grasp is that we are not dealing with a infection of a single bacteria (classic) but overgrowths of dozens, perhaps hundreds of bacteria families. We need to correct the shift… and that is far more complex.

How long should I take one thing?  IMHO: 2 weeks minimum (typical course of antibiotics duration), 4 weeks maximum.

My Icelandic reader also praised the impact of  Zinc carnosine on his gut.

“1)  I believe Zinc Carnosine is of importance for treating Leaky Gut. I had constant nausea for months after using for a while  and quiting the medicine Plaquenil and Kratom.  I think it caused increased permeability of the gut (don´t know which one was the cause – or both).  I experienced increase wellbeing and relaxation after 3 weeks on Zinc Carnosine.  Nausea completely went away and hasn´t been back.It has been used in Japan for abt. two decades now I believe. Somewhere I saw it was researched by making it radioactive and pictures showed it accumulate at the gut lining.  The Carnosine is a big molecule that slows the absorption of the Zinc so it does it´s healing at the gut lining.”

As always, it’s to PubMed to see if there is solid evidence supporting his exceptional experience

Zinc carnosine is also the main component of polaprezinc.

• Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers[2016].
• Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes [2007].
• “A zinc-carnosine chelate compound, PZ, enema may become a useful new add-on treatment to accelerate mucosal healing in UC.” [2014]
• Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxycillin and clarithromycin increases the cure rate of Helicobacter pylori infection[1999].

So the evidence supports his experience. What about impact on the microbiome? There was nothing explicit for this, so I will fall back to the impact of zinc.

Microbiome Impact

“Zinc is an essential trace element required for multiple cellular functions, such as enzymatic reactions, DNA synthesis, and gene expression (1). Over 300 enzymes and thousands of transcription factors contain one or more zinc atoms.” [2012]

• “In the zinc-deficient chickens, the bacterial profiles were less diverse, leading to reduced bacterial activity. Gut bacteria are important for a number of reasons, including breaking down nutrients in food into short-chain fatty acids, which increases gut acidity and contributes to digestion and the solubility of minerals, particularly iron and zinc.” [2017]
• “Bacterial community composition was altered in the Zn deficient group, where significantly greater abundance of Proteobacteria and significantly lower abundance of Firmicutes (Figure 3A) was observed. In the Zn(−) group, the abundance of Bacteroidetes was increased whereas Actinobacteria was diminished, albeit not significantly.”[2015]
  • ” In contrast, in the stool samples there was a higher relative abundance of Bacteroidetes and lower abundance of Firmicutesobserved in ME/CFS patients compared to healthy controls.” [2015] – same pattern as a Zinc Deficient microbiome.

CFS/FM/IBS

• “Serum levels of zinc (P = 0.001) and magnesium (P = 0.002) were significantly decreased by FM groups, ….Association between serum zinc level and number of tender points (P = 0.008)” [2008]
• Zinc Deficiency is Associated with Poor Clinical Outcomes in Patients with Inflammatory BowelDisease [2017].
• “Serum levels of zinc, SOD activity, albumin, and total protein were significantly lower (P < 0.05) in IBD patients than controls”,[2016]
• Iron Deficiency, Zinc, Magnesium, Vitamin Deficiencies in Crohn’s Disease: Substitute or Not?[2016]
• In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation [2005].
• Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS [2005].

Bottom Line

Just as with molybdenum in my last post, supplementation can reasonably be expected to shift the microbiome away from the usual pattern seen with CFS patients. I could not find suitable comparison between different forms of zinc supplementation.

For dosage: 30-40 mg/day see this post

For some probiotics, specifically, all 0f the E.Coli probiotics, we have studies of them persisting for weeks and months:

• “In a randomized double-blind clinical trial, healthy newborns were given the bacteria during their first 5 days of life [46]. The stools were (Mutaflor – E.Coli Nissle 1917) EcN-positive in >90% of infants for as long as 6 months.”[2016]
• “for the control group (not receiving mesalazine), within 2 weeks after secession of EcN administration, the strain could be detected in the stools of only 40% of individuals, dropping to 20% after 9 weeks [35]” [2016]
• Colinfant (another E.Coli Probiotic) “reported that the strain could still be detected in stools 25 weeks after dosage [13].” [2016]
• “a human volunteer study was performed to investigate the colonization potential of Symbioflor 2, which resulted in long-term colonization in all five volunteers, for a period of at least 20 weeks;”[2016]

On the other hand, the commonly taken ones — stay just hours,

• “Seven days after the VSL-3 treatment suspension, no patients and subjects harbored B. infantis Y 1 and B. breve Y 8, indicating a transient presence of these exogenous strains.” [2000]
• “Streptococcal population was detected after 3 days of administration and persisted for 6 days after the treatment suspension.” [2003]
• “The probiotic bacterium [Lactobacillus acidophilus] was detected in feces via ribotyping and RNA gene sequencing during the probiotic administration phase but not 2 weeks after cessation of administration.” [2004]
• ” Dead vegetative cells were detected 9 hr after administration, and C. butyricum cells were not detected in the intestine after 3 days.” [1997]
• “After 24 h, [Bacillus] spores constituted only 12% of the total counts in the stomach, caecum, and mid-colon. Less spores and more vegetative cells were detected after 24 h…The two Bacillus strains can temporarily remain in the GI system, but will be unable to permanently colonize the GI tract.” [2008]

“After oral consumption of probiotics, E. coli and enterococci could be detected in stool samples (57% and 67%, respectively) [after one week of stopping]. In contrast, with only one exception, ingested lactobacilli and bifidobacteria could not be detected in human feces.” [2007]

Bottom Line: E.Coli probiotics taken for a few days every month or two months, will keep the E.Coli in your system constantly. Enterococcus probiotics appear to have similar staying power.  For almost everything else, the benefit will last only for 1-2 days after you stop taking them.  E.Coli may be more expensive, but is likely a wiser buy.

A reader forwarded me their report and asked me to do an analysis and asked some specific questions about what can be done for some items. I had done an earlier post on another patients KyberKompakt Pro report — the results are very similar, consistent with what appears to be the usual shift away from normal seen in CFS patients. I would expect at least 90% of CFS patients to have very similar results (IMHO, this specific test is a good validation of a CFS diagnosis OR if dissimilar, suggests other issues may be occurring.

Each line means 10x, so E.Coli is 3 lines below the bottom of the normal range, or 10 x 10 x 10 – 1000 times less (not a little decrease).

How do the 2 sample compare?

• E.Coli: < 1 x 10⁴, < 2 x 10⁴ – 100x less
• Bifidobactrium:  7 x 10⁶, 4 x 10⁶ – 500x less
• Lactobacillus: 2 x 10⁶ (Normal), 2 x 10⁴ – 10x less
• Hydrogen Peroxide producing Lactobacillus: 2 x 10⁴ (Normal), 2 x 10⁴ – 5x less
• Enterococcus spp: 2 x 10⁵, 1 x 10⁴ – 100x less
• Akkermansis muciniphia:  5 x 10⁴ , 8 x 10⁴ – 10000x less
• Faecalibacterium prausnitzi: 1 x 10⁷ (100x less),1 x 10^{9 (Normal)}

Lactobacillus is always a problem because patients may be taking it as probiotics or yogurt before the testing. Also, the magnitude is much less than the other ones.

We also see that the pH is off significantly.

Addressing Akkermansis muciniphia shortage

• Preparation and preservation of viable Akkermansia muciniphila cells for therapeutic interventions[2017]. “The anaerobic gut bacterium Akkermansia muciniphila is a well-characterised member of the mucosal microbiota and has shown to be a gut symbiont in human…A. muciniphila cells reversed highfat diet-induced obesity and its associated metabolic disorders in mouse models…A. muciniphila cells with high yields and very high stability, with up to 97.9±4.5% survival for a time period of 1 year at -80 °C in glycerol-amended medium.”
  • So work is ongoing to develop a probiotic (therapeutic) use!
• Intestinal Microbiome, <i>Akkermansia muciniphila</i>, and Medical Nutrition Therapy[2016].
• “an increase of Enterobacteriaceae, Desulfovibrio sp., and mainly Akkermansia muciniphila in Constipated-predominant IBS patients compared to healthy individuals.” [2016]
  • So an overgrowth has a distinct symptom — C-IBD! (this may be why this was being tested for)
• Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo [2017].
  • Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers[2015]. “1000 mg of POM extract daily for four weeks….Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers” — 25% were non responders.
• “vitamin D deficient high fat feeding (HFD+VDD), … Akkermansia muciniphila, a beneficial symbiotic, is diminished.” [2016]
  • Vitamin D supplements (my own “normal” is always the top of the Vitamin D range — typically requiring 15,000 IU/day)
• Aguamiel concentrate from Agave salmiana and its extracted saponins attenuated obesity and hepatic steatosis and increased Akkermansia muciniphila in C57BL6 mice[2016].
• ” Flax Seed diet altered the fecal microbial community structure (16S rRNA gene profiling), including … a 30-fold reduction in Akkermansia muciniphila abundance.” [2016] – Avoid flaxseed!!!
• Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice[2015]. i.e. it decreases as inflammation increases.
• “supplying a gluten-free diet to mice increased fecal levels of Akkermansia species (32).” [2015]
• Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism [2011].