Another high bacteria is clostridium asparagiforme reported by Ian Lapkin et al 2017 paper [Index to all posts on Study].  This bacteria was first identified in 2006 and The organism produced acetate, lactate, and ethanol as the major products of glucose fermentation. It ferments glucose. It also produce an enzyme, Threo-3-hydroxy-L-aspartate ammonia-lyase, whose role is unclear but is also produced by other bacteria in the study:

• Alistipes putredinis, which is low.
• Anaerostipes caccae which is high
• Bacteroides caccae which is low
• Bacteroides fragilis, which is high
• Bacteroides vulgatus, which is high
• Dorea formicigenerans, which is low
• Eubacterium hallii, which is high

To have this enzyme shared by so many bacteria in the report is very curious and warrants research.

In terms of its simpler production

• Lactate overproduction may contribute to D-lactic acidosis, and
• Ethanol overproduction to the overgrowth of Pseudoflavonifractor capillosus also cited in the paper.

A closely related bacteria is  vancomycin-resistant[2009]

• “(Clostridium asparagiforme) phylums as containing a peptide that seems to activate killer T cells, which are a natural component of the human immune system, to target and latch onto pancreatic beta-cells, rendering them useless to produce vital insulin.” [2016 blog]
• “A large cluster including Gordonibacter pamelaeae, Clostridium asparagiforme, Eggerthella lenta, and Lachnospiraceae bacterium as well as small clusters containing strains such as Lactobacillus sp., Bifidobacterium dentium and Ruminococcus lactaris were enriched in the gut of RA patients.” [2016]

Bottom Line

We know nothing about this bacteria that can translate into clinical action.

Another low bacteria is dorea formicigenerans reported by Ian Lapkin et al 2017 paper [Index to all posts on Study].  This bacteria was formerly known as Eubacterium formicigenerans [2002].

• Bacteria> Firmicutes> Clostridia> Clostridiales> Clostridiaceae> Dorea> Dorea formicigenerans
• Conditions with low Dorea:
  • Parkinson’s Disease [2017]
  • Functional Abdominal Pain in Children With Autism Spectrum Disorder. [2016] But without pain, Dorea is increased [2017]
• “An adequate bowel cleansing (Moviprep),…notably increased the levels of Proteobacteria, Fusobacteria and bacteria related to Dorea formicigenerans.” [2015]
• “decreased after treatment only in the antibiotic (amoxicillin, tetracycline and metronidazole for 2 weeks)  group. Eubacterium rectale, Dorea formicigenerans,”

That’s it!  Moving up the tree to Dorea, we have:

• “prebiotic (fructo-oligosaccharides (FOS) and inulin mixture)..revealed a lower abundance of Dorea” [2017]
• “bacteria (arabinogalactan and inulin) belonging to Gemmiger, Dorea, Roseburia, Alistipes, Lactobacillus and Bifidobacterium genera were found to be highly abundant or stimulated by the prebiotics in the lean microbiota” [2016]
• “Alcohol …  significant reductions in genra Clostridium IV and XIVb (p<0.001), Dorea (p<0.01), [2017]
• “animal-based diet caused a significant increase in the relative abundance of Bilophila, Odoribacter, Dorea and Ruminococcus (belonging to Lachnospiraceae) and a significant decrease in the level of Bifidobacterium after five days of intake.” [2016]
• “High Molecular Weight Barley β-Glucan .. decreased Dorea” [2016]
  • “whole-grain barley and barley malt, decreases” [2015]
• “Oral Iron …was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp.” [2017]  – IV Iron should be the preferred treatment in CFS
• “L-glutamine .. had statistically significant reduction. [2015]
• “L. rhamnosus hsryfm 1301.. positive correlation was observed between Ruminococcus spp. and serum triglycerides, Dorea spp. ” [2014]

Bottom Line

Above we see a lot of items to avoid. In terms of items to take, we have just a few

• Inulin or arabinogalactan and inulin are beneficial
• Lactobacillus rhamnosus
• If you  are low in Iron, stop taking Oral Supplements and switch to IV Iron.

THIS IS NOT MEDICAL ADVICE — this post is an education summary of what has been reported on PubMed. Always consult with a knowledgeable medical professional before changing diet, supplements and prescription drugs.

In Ian Lipkin et al 2017 study, high bacteroides fragilis was reported (on average). [Index to all posts on Study] This bacteria is well studied with over 5000 articles on Pub Med. Some antibiotics are effective, but there is increasing resistance [MedScape].

It is also strongly implicated with Alzheimer’s Disease and Parkinson’s (see these posts for details). For the most current list of items that impact this bacteria see my Analysis Site.

It produces butaric acid.

• Probiotics
  • “Fecal excretion of Bacteroides fragilis, Clostridium perfringens, and clostridial spores decreased after 7 d of consumption of Streptococcus thermophilus and bifidobacterium breve C50″ [1998]
  • “the administration of bifidobacterium longum CECT 7347 reduced the numbers of the Bacteroides fragilis group” [2014]
    • ” Coculture stimulated the growth of B. longum, retarding that of B. fragilis, with concomitant changes in the production of some proteins and metabolites of both bacteria.” [2016]
    • Effect of the oral intake of yogurt containing Bifidobacterium longum BB536 on the cell numbers of enterotoxigenic Bacteroides fragilis in microbiota.
  • “Lactobacillus casei Zhang …an increase in Bacteroides fragilis [2014]
  • “Lactobacillus casei variety rhamnosus (LCR35)..increased the population of Bifidobacterium, Lactobacilli, Enterococcus and Bacteroides fragilis group” [2015]
  • “Lactobacillus acidophilus, Bifidobacterium lactis and Lactobacillus F19 prevent antibiotic-associated ecological disturbances of Bacteroides fragilis in the intestine.[2003]” – stopped the drop of b.fragilis seen with taking antibiotics.
• Diet
  • “Mediterranean diet.. reduces”[2016]
  • “the relative abundance of Bacteroides fragilis was greater than the control from feeding the Chardonnay grape diet.” [2015] Chardonnay are white wine (green-skinned) grapes.  In the same study,  Cabernet Sauvignon [red wine, purple] grapes did not increase.
  • “a strict vegetarian diet (SVD) for 1 month..an increase in commensal microbes such as Bacteroides fragilis” [2013]
  • “oat bran…lower numbers of Enterobacteriaceae, Akkermansia and Bacteroides Fragilis” [2013]
  • “Population of Bacteroides fragilis significantly decreased after elemental diet” [2012]
  • “polydextrose ingestion…species (B. fragilis, B. vulgatus, and B. intermedius) decreased, whereas LACTOBACILLUS: and BIFIDOBACTERIUM: species increased.” [2000]
  • “Rats on the all-rice diet had significantly lower faecal concentrations of the main menaquinone-producing bacterial species (Bacteroides fragilis and Bacteroides vulgatus) than animals on either of the other two diets ( a rice + beans diet or a stock diet)” [1990]
• “Tannic acid, propyl gallate and methyl gallate, but not gallic acid, were found to be inhibitory to the growth of intestinal bacteria Bacteroides fragilis ATCC 25285″ [1998]
• “whole-grain barley…decreased the Bacteroides fragilis group, but increased the number of Bifidobacterium only when dietary fat was consumed at a low level.” [2015]
• “Nisin growth curves of an a peptide reducing the growth of the B fragilis” [2014]
• “Inulin …decreased numbers of Bacteroides fragilis,” [2002]
• ” With the exception of selective inhibitory action of n-hexane extract of Nigella orientalis on growth of Bacteroides fragilis (MIC = 0.5 mg/mL),” [2009] — specific seed extract is needed and then only some impact.
• “The fecal levels of B. fragilis were significantly increased by the inclusion of cholesterol(1%) in the diets.” [1985]
• Human fecal flora: variation in bacterial composition within individuals and a possible effect of emotional stress 1976]. Stress increase it. Tetracyclines work on some strains but other strains are resistant.

Bottom Line

During my readings, I came across the following results which validate a speculation that I had: individual strains different mixtures produce different chemicals. So starting with hundred of thousands strains, we need to see how each interact with each other….  if we want to be strictly scientific [All of the computer storage in the world would not be enough to store the results]. Alternatively, guided trial-and-error is viable.

• “Therefore, cocultures of Bifidobacterium and Bacteroides can behave differently against fermentable carbohydrates as a function of the specific characteristics of the strains from each species.” [2013]
• “When stressed, overpopulated or pathogenically stimulated, B. fragilis releases a remarkably complex array of endotoxins and exotoxins (such as fagilysin), lipooligosaccahrides (LOS), lipopolysaccharide (LPS), including an extremely proinflammatory B. fragilis LPS (BF-LPS), microRNA-like sncRNA, and a wide variety of bacterial-derived amyloids (9–11, 56, 57, 64–66). ” [2018]

For the most current list of items that impact this bacteria see my Analysis Site.

Another low bacteria from  Ian Lipkin et. al [2017] study  [Index to all posts on Study] was Alistipes putredinis was formerly known as Bacteroides putredinis (Weinberg et al., 1937) [2003]. Like the prior two bacteria, it is a butyrate producer. It is in the the lysine pathway [2014]

• “There was one isolate of Bacteroides putredinis resistant to chloramphenicol” [1999]
• “Adding meat back in to a vegan diet caused an immediate increase in the bacteria (Bilophila wadsworthia, Alistipes putredinis and species in the genus Bacteroides) that grow with exposure to bile, which increases when a person eats more fat.” [From Nature]
• “Alistipes putredinis, and Eggerthella spp. were associated with cruciferous vegetable intake” [2009]

We have very little information on increasing this one, but there is a hint that should be followed up.

Looking at Butyrate Producers

There are four main pathways (acetyl-CoA pathway, orange; glutarate pathway, blue; 4-aminobutyrate pathway, pink; lysine pathway, grey)[2014]. Shown below are these pathways.

One is missing, the lactate->butyrate path which is used by Clostridium Butyricum (while listed below — is blank).

This raises the question: is the low level due to the low level the “intake food the bacteria uses to produce butyrate”?? That is:

• Alistipes putredinis it is lysine, which suggests that lysine supplementation may help. A earlier post found no reports on lysine levels seen in CFS/IBS/FM.
• Clostridium Butyricum it is lactate (not a problem because CFS tends to be high in lactate)
• Faecalibacterium it is Acetyl coenzyme, from acetate, ethanol, valine, leucine, and isoleucine occurs. A earlier post found no reports on aline, leucine,  isoleucine levels seen in CFS/IBS/FM.
• Pseudoflavonifractor capillosus it is  class IV alcohol dehydrogenase [2016] from  ethanol [1994]

Suggested Clinical Trials

As with the last post, 10 patients have their microbome measured before and then 2 weeks after the end of the interventions listed below. There should be a separate trial for each of the following.

• Lysine supplementation
• Valine supplementation
• Leucine supplementation
• Isoleucine supplementation

Additional trials could be done on specific cruciferous vegetables.

Bottom Line

Eat cruciferous vegetables! But no broccoli (see earlier post)! Supplementation with amino acids listed above could help — but we need trials.

THIS IS NOT MEDICAL ADVICE — this post is an education summary of what has been reported on PubMed. Always consult with a knowledgeable medical professional before changing diet, supplements and prescription drugs.

In Ian Lipkin et al 2017 study, high Pseudoflavonifractor capillosus was reported (on average). [Index to all posts on Study] Well, we have just 4 articles in total on PubMed. One of the articles cited that it was the bacteria formerly known as Bacteroides capillosus. With just one result

• “Increased with proton pump inhibitors” [2016]

Relaxing the search criteria, we found 39 articles. “This genus [Pseudoflavonifractor] is one of the most prominent butyrate producers, providing energy to the colonic mucosa and known to regulate gene expression, inflammation, differentiation, and apoptosis in host cells (Luo et al., 2013).”

• Phosphorus in diet increases [2016]
• B. capillosus strongly stimulated rat mast cells to histamine secretion [2000] — so this may be a contributor to histamine issues with CFS. (see this post)

Antibiotics

While usually not preferred, we do have some information on which ones may be effective:

• Moxifloxacin — 67% of strains are resistant [2008]
• ” Both faropenem and imipenem had MICs of < or=4 micro g/ml for all isolates of Bacteroides capillosus (10 isolates), ” [2002]
• “All beta-lactamase-positive strains were found to be susceptible to imipenem and chloramphenicol….beta-Lactamase-positive Bacteroides strains showed 95% susceptibility to metronidazole and rifampicin; 90% susceptibility to piperacillin and cefoxitin; 85% susceptibility to tetracycline and erythromycin; 80% susceptibility to clindamycin and amoxycillin/clavulanic acid, and 76% susceptibility to ticarcillin.” [1999]
• “Against beta-lactamase-producing strains of the Bacteroides fragilis group, B. capillosus, and Prevotella species all combinations of ceftriaxone and tazobactam showed enhanced in vitro activity and were eight- to 2048-fold more active than ceftriaxone alone.” [1994]
  • “All of the beta-lactamase-producing bacteroides strains were sensitive to a combination of amoxycillin with clavulanic acid (Augmentin).” [1990]
• “chlorofluoroquinolone, BAY y 3118.. All strains of Bacteroides capillosus, Prevotella spp., Porphyromonas spp., Fusobacterium spp., Clostridium spp., Eubacterium spp., Peptostreptococcus spp., and Veillonella parvula were susceptible” [1994]
• “Biapenem was also active against all of the B. capillosus, Prevotella, Clostridium, and Eubacterium strains and anaerobic cocci tested. Against all of the anaerobes tested, biapenem was 32- and 4-fold more active than clindamycin and metronidazole, respectively. ” [1994]
• “Bacteroides capillosus) were resistant to penicillin, but none were resistant to clindamycin.” [1990]
• “Bacteroides capillosus and Bacteroides ruminicola subsp. ruminicola) in the high sucrose diet (Diet-2000) group increased with time; those in the tetracycline group decreased with time.” [1989]  — reduce sugar intake
• “Azlocillin, mezlocillin, and cefoxitin had comparable activities, with resistance among members of the B. fragilis group and B. capillosus.” [1984]
• Antibiotic resistance B. capillosus is resistant to benzylpenicillin (2 units), kanamycin (1mg) and neomycin (1mg) but sensitive to erythromycin and rifampicin  [Book 2014]

Herbs and Spices — nothing found 😦

Overfed?

Bacteria need food to grow. Other bacteria could be overproducing food that it needs.

• Pseudoflavonifractor capillosus it is  class IV alcohol dehydrogenase [2016] from  ethanol [1994]

This lead me to:

• ” Highest amounts of ethanol were produced by S. cerevisiae, L. fermentum, and W. confusa on glucose and by S. cerevisiae and W. confusa on fructose. Due to mannitol-dehydrogenase expressed in L. fermentum, ethanol production on fructose was significantly (P < 0.05) reduced. Pyruvate and citrate, two potential electron acceptors for regeneration of NAD⁺/NADP⁺, drastically reduced ethanol production with acetate produced instead in L. fermentum grown on glucose and W. confusa grown on glucose and fructose, respectively. In fecal slurries prepared from feces of four overweight volunteers, ethanol was found to be produced upon addition of fructose. Addition of A. caccae, L. acidophilus, L. fermentum, as well as citrate and pyruvate, respectively, abolished ethanol production.” [2016]

And thus speculative:

• Reduce sucrose, glucose and fructose in your diet.
• L. Fermentum probiotics (available)
• Taking magnesium citrate or other citrate supplements. Ditto for pryuvate.

Bottom Line

Faecalibacterium and Pseudoflavonifractor are both butyrate producers. In CFS the Faecalibacterium is low and Pseudoflavonifractor is high. The only available treatment appears to be antibiotics. No herbs, spices, supplements or diet impact studies could be located. My own path would be to take the items above and intersect them with Cecile Jadin’s protocol — we have some items in common, such as:

• Tetracyclines (my favorite in minocycline)
• Augmentin
• etc

THIS IS NOT MEDICAL ADVICE — this post is an education summary of what has been reported on PubMed. Always consult with a knowledgeable medical professional before changing diet, supplements and prescription drugs.

Clinical Studies Desired

In this very simple:

• Ten patients in each group with uBiome done before. 2 weeks on one of the antibiotics suggested. 2 weeks later, another uBiome.
  • Hopeful outcome: which antibiotics have the best impact on Faecalibacterium and Pseudoflavonifractor.
    • Expected to find 1 in 5 being a double positive change.
• Same as above, but taking Lactobacillus Fermentum for a month.