Hi
@cigana - I don't know for sure, but so many of my symptoms that seem to line up with this hypothesis and reading this thread and research papers on the subject have connected a few dots. In particular:
- Symptoms significantly improve when on ketogenic diet
- Symptoms significantly improve the most when fasting
- Eating meals with regular amounts of carbohydrates seems to trigger PEM and ME worsening (sometimes immediate, sometimes delayed after cumulative meals)
- I do not have all the symptoms of acute d-lactate acidosis, in particular I do not have the drunkenness and slurred speech issues. But I've always had many overlapping since getting ME and are triggered or get worse with carbs: balance/equilibrium and other neurological problems, irritability/agitation/emotional lability, difficulty concentrating, memory problems, and crushing fatigue.
- Disease and symptoms have been continually and gradually getting worse after entering chronic phase of ME a few years ago, only earlier this year did I find that fasting was making symptoms better, and only last month did I find that a ketogenic diet also significantly helps.
All of this has just made me think what is going on. Why does what I eat make such a significant difference to my ME symptoms? I totally agree with
@Avenger I think the medical community is likely making a mistake thinking d-lactate problems only occurs in short bowel syndrome and related.
Hi, I thought that you might like this from someone called Lassesen. You have all seen the first two passages, but please read on. For me it stands to reason that the medical community who have patients with neurological symptoms should be looking for something like D-Lactic acidosis which causes fluctuating levels of the neurotoxin D-Lactic acid. D-Lactic acidosis is a variant of SIBO and I firmly believe that there are a number of variants and combinations of Overgrowth which may explain variations and similarities of symptoms. Having D-Lactic acidosis would not preclude from having SIBO. D-Lactic acidosis can coincide with other forms of Bacterial Overgrowth. Antibiotics may help in the short term, but they will eventually lead to further damage of Gut Biosis. Lassesen suggests using Metronidazole followed by any form of E.Coli Probiotic which has been used before to cure a range of Gastrointestinal disease. A Fecal Transplant may be a better option in providing a more diverse balanced biosis.
Approaches to D-Lactic Acidosis
My last post cites a
2009 article that found:
“Faecal microbial flora of CFS patients and control subjects. The mean viable count of the total aerobic microbial flora for the CFS group (1.93×108 cfu/g) was significantly higher than the control group (1.09×108 cfu/g) (p<0.001). There was a significant predominance of Gram positive aerobic organisms in the faecal microbial flora of CFS patients. …This study confirms the previous observation (22), and those reported by other investigators (23) that there was a marked alteration of faecal microbial flora in a sub-group of CFS patients….. In this study the mean total count for Enterococcus and Streptococcus spp. for the CFS group was 52% of the total aerobic intestinal flora, which is significantly higher than the 12%seen in the control subjects (p<0.01). ”
largely old hat to readers of this blog, a microbiome dysfunction.
But the study went on to some new interesting stuff, a possible mechanism:
“In this study the NMR-based metabolic profiles of the three intestinal micro-organisms, E. faecalis., S. sanguinis. and E. coli showed that the Gram positive bacteria (Enterococcus and Streptococcus spp.)
produce more lactic acid than the Gram negative E. coli. Not surprisingly, these Gram positive bacteria were shown to
lower the ambient pH of their environment in vitro as compared to that of E. coli. This suggests that when Enterococcus and Streptococcus spp. colonization in the intestinal tract is increased, the heightened intestinal permeability caused by increased lactic acid production may facilitate higher absorption of D-lactic acid into the bloodstream, henceforth perpetuating the symptoms of D-lactic acidosis. Increased intestinal permeability is also associated with endotoxin release from Gram negative enterobacteria,
leading to inflammation, immune activation and oxidative stress, which are cardinal features in a large subset of CFS patients ”
This ties in well with observations, for example, some people getting relief by various breathing techniques intended to alter pH of the stomach and intestines.
So, putting on the blinkers and focusing solely on the overgrowth of Enterococcus and Streptococcus, how can someone impact this without getting antibiotics (in some countries, prescribing antibiotics for a condition that is not recognized as needing them, can cost a MD their license)?
- “Among the plants chloroform and isoamyl alcohol extracts of Cumin ( Cuminum cyminum), Clove (Syzygium aromaticum) and Turmeric (Curcuma long Linn) had significant effect against … Streptococcus pyogenes” [2013]
- “Cortex phellodendri showed antimicrobial activity against Streptococcus mutans, while Radix et rhizoma rhei was effective against Streptococcus mitis and Streptococcus sanguis. Fructus armeniaca mume had inhibitory effects againstStreptococcus mitis, Streptococcus sanguis, Streptococcus mutans and Porphyromonas gingivalis in vitro.” [2010] – most of these are Chinese/Japanese medicinal herbs
- “eight herbal extracts could inhibit the growth of Streptococcus sanguinis. Jasmine, jiaogulan, and lemongrass were the most potent,” [2008]
- ” (common Fig) F. carica and (Olive leaf) Olea europaea leaves inhibited growth of… Streptococcus pyogenes” [2011]
- “onion could inhibit E. coli, … Streptococcus faecalis [1985] – not recommended because of impact on E.coli
- ” Lemongrass, oregano and bay inhibited all organisms” [1999]
- “especially those of Origanum glandulosum and (Mediterranean thyme) Thymbra capitata with interesting minimum inhibitory concentration, biofilm inhibitory concentration, and biofilm eradication concentration values” [2014]
Early post on treating
Enterococcus cites:
Azadirachta indica,
Ocimum tenuiflorum,
Monolaurin. Streptococcus is associated with excessive histamine, see
earlier post.
MedScape Article reveal no effective accepted treatment. A fuller article is (
here JASN).
Brain Fog etc caused by lactic-acid
Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review [2017]
cites:
- “Higher levels of d-lactate producing bacteria (such as Streptococcus and Enterococcus) have been identified in stool samples from patients with ME/CFS “
- Shared with acidosis and ME/CFS “B1. Encephalopathy/Mental confusion/disorientation/dazed/Concentration difficulties/Slow processing and responding to questions/slow speech
B2. Headaches/Muscle pain
B3. Drowsiness/sleepiness/somnolence
B4a. Blurred vision
B4b. Weakness/hypotonic (lowered muscle tone)/flaccidity/impaired gait (staggering/wide/ataxic/unsteady/instability)/ataxia (movement and co-ordination difficulties)/impaired balance”
Antibiotic Approach
The prime bacteria to reduce are Enterococcus and Streptococcus. After the antibiotic, you want to have E.Coli back fill the spaces created by the above being killed.
Probiotic approach
“… Recently, considerable progress has been made in the isolation of these strictly anaerobic butyric acid-producing bacteria from the human gut. It has been shown … that lactic acid, produced in vitro by lactic acid bacteria, is used by some strictly anaerobic butyrate-producing bacteria of clostridial cluster XIVa for the production of high concentrations of butyric acid (Louis & Flint, 2009). This mechanism is called cross-feeding …” [
Source]
This implies that
miyarisan (clostridium-butyricum) should be of benefit.
E.coli probiotics (symbioflor-2, mutaflor) will displace the high producers and produce a lot less (around 2%) of what the high producers do.
“Lactomin[300 mg Lactobacillus acidophilus, 300 mg Bifidobacterium longum] was discontinued, and she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis ” [
2010]
Supplement Approach – Thiamine (Vitamin B1) and NAC
100 mg every 12 hours is reported to reverse this for other conditions.
- “Thiamine replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients.” [1997]
B1 (at sufficient high dosages) have had major improvement of symptoms. See these posts also:
“We concluded that the patient had metabolic acidosis induced by accumulation of 5-oxoproline. We modified her antibiotic treatment, administered acetylcysteine (NAC), and her acidosis resolved.” [
2016]
Classification
Cohen and Woods devised the following system in 1976 and it is still widely used:[
1]
- Type A: lactic acidosis occurs with clinical evidence of tissue hypoperfusion or hypoxia is likely what is seen in CFS. The hypoperfusion is well reported as a signature of CFS.
Testing for D-lactic Acidosis
This is a specialized test that is usually not done [
Mayo Clinic] “Routine lactic acid determinations in blood will not reveal abnormalities because most lactic acid assays measure only L-lactate. Accordingly, D-lactate analysis must be specifically requested (eg, DLAC / D-Lactate, Plasma). ”
Word on Likely Dosage
The last article cited an article treating it. I noticed that often there was very
high dosages. My gut feeling (no evidence to back it up) is that for any of the above, we may well be talking 8 – 16 “00” capsules per day of each one, with a possible change of the herb/spice every 7 days. Remember we are talking about reducing from 52% to 12%, not a walk in the park.
As always, consult with your knowledgable medical professional before starting or changing supplements.
Probiotics to avoid
L. delbrueckii bulgaricus (ATC 11842) has a 26:7 ration of D-Lactic acid to L-Lactic Acid [
Source]
Bottom Line
“Management includes correction of metabolic acidosis by intravenous bicarbonate, restriction of carbohydrates or fasting, and antibiotics to eliminate intestinal bacteria that produce D-lactic acid.” [
2017]
“Main treatments are: 1) changing the abnormal intestinal flora with the administration of oral antibiotics, 2) attempt to diminish the quantity of substrate for intestinal fermentation by using the low-carbohydrate diet or enteral formulas containing fructose or starch instead of glucose as the main source of carbohydrate, 3) correction of the underlying abnormality by reanastomosing the intestine in case of intestinal bypass, 4) nonspecific therapy of acidosis with
high doses of bicarbonate, 5) correction of the acidosis and simultaneous clearance of D-lactate with hemodialysis
3,
4). Antibiotics control symptoms and prevent recurrence of the syndrome in most patients, but in some patients acidosis recurs despite the antibiotic use. Antibiotics that have been tried include neomycin, vancomycin, ampicillin, kanamycin, and metronidazole. The optimum duration of antibiotic therapy is uncertain because the symptoms may recur in a few days after discontinuation of antibiotics in some patients, while others may remain without symptoms for several years in the absence of oral antibiotics
4).” [
2006]
B1, NAC and sodium bicarbonate taken together are a likely good starting point. Of the antibiotics listed above, I would opt for metronidazole because of the positive results reported
in surveys of CFS patients, Probiotics would be any E.Coli probiotic. Any (or multiple) of the above herbs.
Insights from 100 Years of Research with Probiotic E. Coli
Trudy M. Wassenaar
Author information Article notes Copyright and License information Disclaimer
This article has been
cited by other articles in PMC.
Go to:
Abstract
A century ago, Alfred Nissle discovered that intentional intake of particular strains of
Escherichia coli could treat patients suffering from infectious diseases. Since then, one of these strains became the most frequently used probiotic
E. coli in research and was applied to a variety of human conditions. Here, properties of that
E. coli Nissle 1917 strain are compared with other commercially available
E. coli probiotic strains, with emphasis on their human applications. A literature search formed the basis of a summary of research findings reported for the probiotics Mutaflor, Symbioflor 2, and Colinfant. The closest relatives of the strains in these products are presented, and their genetic content, including the presence of virulence, genes is discussed. A similarity to pathogenic strains causing urinary tract infections is noticeable. Historic trends in research of probiotics treatment for particular human conditions are identified. The future of probiotic
E. coli may lay in what Alfred Nissle originally discovered: to treat gastrointestinal infections, which nowadays are often caused by antibiotic-resistant pathogens.
Keywords: probiotics,
Escherichia coli, Nissle, Symbioflor, human studies, applications
Go to:
Introduction
Many probiotic products are based on particular strains of lactic acid bacteria, such as
Lactobaccillus and
Lactococcus species (both
Firmicutes) or
Bifidobacterium species (belonging to the
Actinobacteria). Other genera of bacteria (and even yeast species) are also used for probiotic applications, including
Escherichia coli, a member of the
Gammaproteobacteria. This working horse of bacteriology is not only the most frequently studied bacterial species on the planet but also a rather complicated one, since it includes both commensal and pathogenic strains whose genomes can widely vary in size and gene content [
1].
That
E. coli is chosen as a probiotic would be in line with its presumed ubiquitous presence in the gut. But how often is
E. coli actually present in a human gut, in what numbers, and is it a “major player” in that environment? Despite a plethora of data available on this species, these data are not easy to find. In his book on normal human microflora, Tannock describes that
E. coli is typically found in the ileum (the last third of the small bowel) as well as in the colon, but not outnumbering other more numerous species [
2]. Caugent and colleagues describe coexistence of transitory and persistent clones, with rapid changes in the genetic composition of the population, but quantitative data are not given [
3]. The colon contains approximately 1.5 kg of wet-weight bacterial cells, while feces contains about 1012 bacteria per gram [
4]. According to a publication in 1974 by Hill and Drasar, the human lower intestine contains, on average, 2·103 (in the terminal ileum) to 1.6·106 (in the cecum) colony-forming units (CFU)
Enterobacteria per gram intestinal material; for feces (which reflects luminal flora of the recto-sigmoid region rather than the mucosal and villous crypts flora), the average is 2.5·107 CFU/g [
5].
E. coli is only one of several
Enterobacteria species typically present, and to put these numbers into perspective, these
Enterobacteria are outnumbered by a factor of 100 to 1000 by
Bacteroides and Gram-positive nonspore-forming anaerobes [
2,
5]. In line with this,
E. coli is not among the top 25 most prevalent bacterial species typically present in feces of human subjects consuming a Western diet [
2]. The numbers quoted here were based on cultural findings, and the limitations of this procedure have long been recognized: a significant proportion of the bacteria in the gut are uncultivable. Nevertheless, since culturing of
E. coli is well established, culture-dependent results should be sufficient for a quantitative estimate. It is, therefore, surprising how few quantitative data exist on colonization by
E. coli in healthy individuals. In a recent publication comparing obese with normal-weight people, Zuo and coworkers reported around 108 CFU
E. coli per gram feces for both groups [
6]. Although, in recent times, metagenomics studies provide insights in the uncultivable fraction of the gut microbiome, those methods are rather insensitive and usually do not detect species present in fewer than 105 cells [
7]. Moreover, findings are often reported as phyla (e.g.,
“Proteobacteria”) or taxonomic families
(“Enterobacteriaceae”) rather than individual genera or species. It has been observed that there is only 15% overlap between metagenomics and culture-dependent methods [
7]. In addition, sequence-dependent methods frequently over-estimate the diversity of species being present, for a number of reasons discussed elsewhere [
8]. For these and maybe other reasons, metagenomic data hardly ever provide a quantitative estimate on the number of
E. coli bacteria in the gut. In the outstanding, recently published catalogue of the human gut microbiome determined from 124 European individuals (based on fecal samples),
Escherichia was not among the 56 most abundant species [
9]. From browsing through a large amount of literature, it seems safe to say that
E. coli is “often” present in a human gut, though in relatively low numbers, and whether it a “major team player” in that environment remains to be seen.
Despite this,
E. coli bacteria are the basis of at least three commercially available probiotic products, known under the commercial names Mutaflor, Symbioflor 2, and Colinfant, respectively. These products have been used in multiple scientific investigations to unravel their presumed positive effects on human health. Mutaflor, produced by Ardeypharm GmbH (Herdecke, Germany, a pharmaceutical company founded in 1970), contains viable cells of a single
E. coli strain called
E. coli Nissle 1917. Symbioflor 2 (DSM 17252), produced by SymbioPharm GmbH (Herborn, Germany, founded in 1954), contains a concentrate of six
E. coli genotypes. Colinfant is marketed by Dyntec (Terezín, Czech Republic) and contains a single
E. coli strain; it is specifically marketed for use in newborns and infants and is mainly used in the Czech Republic.
You may want to read the rest of the abstract.
Paul.
