Faecalibacterium prausnitzii – A key player for a SMALL subset

A reader write a comment on one of my earlier posts

“I’ve had CFS since I was 11. I, at 46, just had a gut microflora test from ubiome. The analysis below is from ubiome data, through the metagenomics RAST server. I note that the Faecalibacterium prausnitzii are rather abundant, as well as various butyrate producing bacterium. E. coli is nonexistant, and bifidobacterium are quite sparse.”

and then provide details from ubiome.

I responded (see above) with a quick first past of what I found on PubMed for Faecalibacterium prausnitzii. Below is a greater dive. REMEMBER this appears to be a SMALL subset of CFS patients, without uBiome results, do no assume it applies to you. Most CFS patients are LOW for Faecalibacterium prausnitzii [see this post], as is also seen with Crohn’s Disease and UC, there is a very low level of Faecalibacterium prausnitzii.

  • Abundance and diversity of GI microbiota rather than IgG4 levels correlate with abdominal inconvenience and gut permeability in consumers claiming food intolerances. “The abundance and diversity of microbiota significantly correlates with low Calprotectin values (R=-0.35; p=0.01) and with higher abundance of Faecalibacterium prausnitzii (R=0.78; p<0.01) and Akkermansia (R=0.82; p<0.01). ” (http://www.ncbi.nlm.nih.gov/pubmed/24502607 ). For your none statistical types, R=0.78 is almost a straight line relationship!!
  • “One study demonstrated a strong association between high abundance of Faecalibacteriumprausnitzii and decreased levels of butyrate and propionate, and established eczema.” [2016]
  • “F. prausnitzii phylotypes[strains] differed in obese with and without developed diabetes type two.” [2016]
  • “In particular, subject 137 was a standout example whereF. prausnitzii was found to contribute less than 5% to the overall community, whereas its metaproteome exceeded more than 10% of all proteins, indicative of the very high gene expression activity of this bacterial group. The majority of the F. prausnitzii KOs were involved in amino acid metabolism, but almost half of theF. prausnitzii peptides could not be designated to any specific function”
  • “whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic [gout] syndromes.” [2016]
  • “Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii.” [2015]
  • “In the metabolic syndrome patients, red wine polyphenols significantly increased the number of fecal bifidobacteria and Lactobacillus (intestinal barrier protectors) and butyrate-producing bacteria (Faecalibacterium prausnitzii and Roseburia) at the expense of less desirable groups of bacteria such as LPS producers (Escherichia coli and Enterobacter cloacae).” [2016] i.e. Grape Seed Extract
  • Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis[2016].
  • “Phylogroup I was found in 87% of Healthy subjects but in under 50% of IBD patients (P = 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P = 0.005). This study reveals that even though the main members of the F. prausnitzii population are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases.” [2015] – Different strains impacts the gut differently. A shift to the bad strains results in IBD.

Treatment Options

  • “However, fast non-preferential degradation of all chain length fractions of oligofructose (extracellularly) and efficient degradation of the short chain length fractions of inulin by B. angulatum LMG 11039(T) and B. longum LMG 11047 made it impossible for F. prausnitzii DSM 17677(T) to compete for the available substrate.” [2016]
  • “numbers of lactobacilli, bifidobacteria (P<0.001) and Faecalibacterium prausnitzii (P<0.05) were higher in the low-fat/high-fiber pigs  than in high-fat/low-fiber pigs,” [2016]
  • “This case study investigated changes of gut microbiota with an omega-3 rich diet. Fecal samples were collected from a 45-year-old male who consumed 600 mg of omega-3 daily for 14 days. After the intervention, species diversity was decreased, but several butyrate-producing bacteria increased. There was an important decrease in Faecalibacterium prausnitzii and Akkermansia spp. Gut microbiota changes were reverted after the 14-day washout.” [2016]
  • “In particular, several experiments involving downshifts to pH 5.5 resulted in Faecalibacterium prausnitzii replacing Bacteroides spp. as the dominant sequences observed.” [2016]  i.e. increasing pH in stomach…
  • “he aim of this study was to test the effect of consuming two healthy diets: a Mediterranean diet and a low-fat high-carbohydrate diet, for 2years in the gut microbiota of MetS patients and those in the control group….Our results suggest that the Mediterranean diet could be a useful tool to restore potentially beneficial members of the gut microbiota, although the stability of these changes over time still remains to be assessed.” [2016] — note Low Fat may be the dominant cause of the study result (instead of the Med. diet).
  • “correlation to vacuum cleaning frequency, with an increase in Faecalibacterium prausnitzii for mothers” [2015] — vacuum less often!
  • Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: a pilot study[2015]. – do not fast
  • “The optimal pH for growth [for F P] ranged between 5.5 and 6.7, while most isolates were inhibited by of the lowest concentration of bile salts tested (0.1%)… Antimicrobial resistance profile showed that most isolates of Faecalibacterium sp. were resistant against ciprofloxacin and sulfamethoxazole-trimethoprim. More than 50% of the isolates were resistant to tetracycline, amikacin, cefepime and cefoxitin. A total of 19 different combinations of multidrug resistance were observed among the isolates.” [2014]
    • “A relatively higher resistance to chotosan hydrolyzates was detected in F. prausnitzii” [2012]
    • “The relative abundance of Faecalibacterium prausnitzii was unaffected except with thymol [Thyme Oil] at 500 p.p.m. of essential oils tested”

Bottom Line Suggestions

This is explicit to those with major Faecalibacterium prausnitzii overgrowth and assuming that is target #1. 

  • Do not bother asking for antibiotics, they are likely to have little effect and will likely cause greater harm.
  • Change you diet to low fiber and high fat (contrary to the typical “healthy eating” advice). Do not fast.
  • Thyme oil is your best choice.
  • Supplement with bile salts, for example Swanson Iron Bile Salts, which should increase your pH also.
  • 600 mg of Omega 3 daily

As always, consult with your knowledgeable medical professional, before starting.

 

Moderating Histamines – more herbs

This post will likely be expanded and revised over the next week.

From some of the feedback that I got on the last post on  astragalus, I thought that I would dive into PubMed to find additional histamine moderating herbs.  If there is severe histamine sensitivity, it can make following my model very challenging.  My impression is to first ignore the microbiome and moderate the histamine response, then start working on the microbiome with some histamine-tolerance having been obtained. Many of the herbs may be challenging to get for many people.

 

For more , see the publications of Tae Young Shin on Pub Med, evaluating tradition Korean / Chinese herbs for histamine and allergy impacts appears to be his speciality.

Astragalus – Controlling histamines

A reader on CFSRemission Facebook site stated that astragalus helped her greatly with histamine issues.

“It works for me like a bucket.
while i am taking it, my symptoms are markedly less.
once i stop, symptoms start appearing.
once that happens, it takes about 10 days of astragalus to start reducing the symptoms again.”

In this post I am going to summarize what we know about this herb from PubMed. Each section below is done by search term

Astragalus Histamine or Allergy

Astragalus Antibiotic

Bottom Line

There is considerable literature supporting the role of Astragalus in reducing/moderating histamines. It does not appear to have significant antibiotic impact nor microbiome impact. It does have positive effects on the brain / cognitive functions.

If have histamines issues, I would suggest that you give it a try

 

 

Gluten: Infants, probiotics and the microbiome

A CFS reader wrote with some really tough questions concerning their infant….

“This week, I’m off on another tangent – gluten intolerance, especially in babies. My daughter turns 6 months old in 2 weeks time and I’m ready to start introducing solids. The problem I have is that the latest information is so conflicting. (Note: these studies have only been done specifically on Celiac Disease). “

“Thoughts that I have in my head are:

  • I am gluten sensitive with CFS and this is linked to my gut microbiota;
  • My baby inherited my gut microbiota when she was born;
  • Has she inherited all of my newly introduced probiotics via breastfeeding since she was born?
  • Being a parent is so much pressure!!! I have this little girl’s lifelong health in my hands!!!
I’ve been reading up on your info on gluten and learned that Bifidobacteria play a role in gluten allergies”

“So, I guess my question is –

When I introduce gluten into my daughter’s diet, do you think that supplementing her with multiple Bifidobacteria strains will help her digestive transition and help her to avoid sensitivity to gluten?”

The Research

  • “this research observed that E. coli releases uracil. L. plantarum specifically recognizes E. coli-derived uracil, which increases the growth rate and production of antimicrobial substance of L. plantarum. In addition, through the inhibitory activity test, this study postulates that the antimicrobial substance is a protein and can be considered a bacteriocin-like substance. Therefore, this research assumes that L. plantarum exerts its antibacterial ability by recognizing E. coli and increasing its growth rate as a result, and this phenomenon could be one of the reasons for L. plantarum settling in the intestine of infants as a beneficial bacterium.” [2016]
  • ” the supplementation with Lactobacillus rhamnosus GG has been associated with the development of sepsis with a cause-effect relationship in six newborns and children. In this study, we report two further cases and discuss the emerging issue of probiotic supplementation safety in neonates. We conclude that physicians must be aware that supplementation with L. rhamnosus GG can cause sepsis in high-risk patients on rare occasions.” [2016]
    • “Effects have been most consistent with combined prenatal and direct postnatal supplementation of the infant and appear strain-specific, with Lactobacillus rhamnosus most often showing an effect.” [2013]
  • “Among the twelve Bifidobacterium sp. strains, the largest spectrum of antimicrobial activity against 9 of the 18 enteropathogenic strains was revealed for a B. breve strain recently isolated from infant intestinal feces.” [2016]
  • ” In a recent meta-analysis, the use of multi-strain probiotics appeared to be most effective for eczema prevention.” [2016]
  • “Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal consumption of probiotics during breastfeeding and age at first solid food introduction .” [2016 – full article]
    • Increased risk: OLDER age at first solids and concurrent breastfeeding with cows’ milk from any source.
  • “There is evidence that the addition of prebiotics to infant formula brings the GI microbiota of formula-fed infants closer to that of breast-fed infants.” [2015]
  • “we gave Bifidobacterium breve M-16V and Bifidobacterium longum BB536 prenatally to 130 mothers beginning 1 month prior to delivery and postnatally to their infants for 6 months….These data suggest that the prenatal and postnatal supplementation of bifidobacteria is effective in primary preventing allergic diseases. Some limited changes in the composition of fecal microbiota by the bifidobacterial supplementation were observed.” [2014]
  • “the probiotic (Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20;) … seemed to prevent atopic sensitisation to common food allergens”

 

Microbiome

  • “Alterations in specific bacterial groups metabolising gluten such as Clostridium or Lactobacillus were reported in Coeliac disease (CD) patients. ” [2015]
  • “The treated CD patients showed a reduction in the diversity of Lactobacillus and Bifidobacterium species. The presence of Bifidobacterium bifidum was significantly higher in untreated CD patients than healthy adults.” [2012]
  • “Bacteria involved in gluten metabolism are mainly Firmicutes and Actinobacteria” [2014 a deep dive study – the chart below is from it]
    F3.large

    • “We isolated 144 strains belonging to 35 bacterial species that could be involved in gluten metabolism in the human gut (Table ⇑). Most of the strains were classified within the phylum Firmicutes (c. 73%), mainly from the genera Lactobacillus, Streptococcus, Staphylococcus and Clostridium. Some 15% of the isolates were classified within the phylum Actinobacteria, mostly from the genus Bifidobacterium. Only 12% of the isolates were Gram-negative bacteria from the phylum Proteobacteria.”
    • “61 of these 144 strains showed an extracellular proteolytic activity against gluten proteins and gelatine. This glutenasic activity was present in strains from Bacillus licheniformis, B. subtilis, B. pumilus, Bifidobacterium longum, Clostridium sordellii, C. perfringens, C. botulinum/sporogenes, C. butyricum/beijerinckii, Enterococcus faecalis, E. faecium, Propionibacterium acnes, Pediococcus acidilactici, Paenibacillus jamilae, Staphylococcus epidermidis, S. hominis and Stenotrophomonas maltophilia.”
    • “Although bacterial strains belonging to Enterococcus faecalis or Bacillus licheniformisexhibited activity, the peptide was not completely hydrolysed. In contrast, other bacteria, such asLactobacillus mucosae (strains B1c and D5a1), L. rhamnosus (strains LA2a, LE3 and D1a) andClostridium botulinum/sporogenes (all isolated strains) appeared to have a higher activity with regard to the 33-mer peptide than other bacteria tested”
    • “However, not all the bacteria involved in gluten metabolism are health promoting. Bacterial proteases of certain groups isolated in this work, including Staphylococcus epidermidis, Enterococcus faecalis,Escherichia coli, Clostridium perfringens and C. sordellii, may be related to inflammatory bowel disease (Pruteanu et al., 2011; Steck et al., 2012).”
    • “We are currently studying whether these bacteria have a protecting and/or a pathogenic role in CD.”
  • Lower bifidobacteria counts in adult patients with celiac disease on a gluten-free diet [2014].
  • “That study found that the probiotic VSL#3 was highly effective in hydrolyzing gliadin polypeptides compared to other commercial probiotic products such as Oxadrop (B. infantis, L. acidophilus, L. brevis, and S. thermophilus), Florisia (L. brevis, L. salivarius subsp. salicinius, and L. plantarum), and Yovis (B. breve, B. infantis, B. longum, L. acidophilus, L. plantarum, L. casei, L. delbrueckii subsp. bulgaricus, Streptococcus salivarius subsp. thermophilus, and Enterococcus faecium).” [2014]
    • “Higher Bacteroides counts are detected in CD children (13, 26) than in controls.”
    • “Data on the levels of Atopobium, Staphylococcus, E. coli, Eubacterium rectale–C. coccoides, the Clostridium histolyticum group, Clostridium lituseburense, and sulfate-reducing bacteria are still contradictory, as there have been reports showing increased levels in CD patients (13) or no difference (26, 28, 30) in comparison to controls.”
    • “The ratio of beneficial lactobacilli and bifidobacteria to possibly harmful Gram-negative bacteria, such as Bacteroides-Prevotella and E. coli, was found to be significantly higher in controls than in CD children (26). It has been shown that levels of specific species of lactobacilli and bifidobacteria may be higher, lower, or not detected in CD patients in comparison to controls (Table 1). However, the exact value of this information still remains unclear.”

Best attempt to answer…

  1. Has she inherited all of my newly introduced probiotics via breastfeeding since she was born?
    1. “Probiotic bacteria administered to mothers during late gestation are transferred to infants born vaginally and influence the assemblages of GIT bacteria. However, colonization of the neonatal GIT and persistence past weaning does not occur in all offspring and varies among probiotics and animal models.” [2010]
    2. “Temporary colonization of an infant with L. GG may be possible by colonizing the pregnant mother before delivery. Colonization is stable for as long as 6 months, and in unexplained circumstances may persist for as long as 24 months.” [2004]
    3. “Alterations of the maternal GIT microbiota composition via supplementation with probiotics and prebiotics have been shown; however, transfer of these benefits to the offspring remains to be demonstrated.” [2012] [Full Text]
      1. “experiments with pregnant mice orally administered a labeled Enterococcus faecium strain showed a low level transfer of the labeled strain to the fetal intestine and a higher level transfer to the mammary glands”
      2. “the maternal immune status seems to affect infant GIT microbiota composition as well as the incidence of allergic diseases. Allergic mothers, e.g., had lower amounts of bifidobacteria in their breast milk and feces and, consequently, decreased counts and diversity of bifidobacteria in the offspring feces (74, 75) compared with nonallergic mothers. The establishment of specific microbiota in infants, such as bifidobacteria (76), has been shown to alter the signaling reactions that determine T-cell differentiation and/or the induction of tolerance (77, 78).”

Recommendations To Discuss with Your Medical Professional

It appears that the issue is with Bifidobacteria — but at the species or strain level. That is, some are good and some are bad. See [2014] for a lot of detail in Table 1, including citing explicit strains that appear to be helpful. Of course, the problem is finding these strains commercially.

  • L. plantarum
  • Bifidobacterium Breve, see also [2015]
  • Bifidobacterium longum BB536
  • No Bifidobacterium bifidum
  • NO L. rhamnosus GG  – because multiple adverse results have been reported.

While neither Prescript Assist nor General Biotics’s equilibrium were cited – they may qualify under multi-strain probiotics.

A dutch page on gluten cites Symbioflor-1 (Enterococcus faecalis )for glutten (page) without giving references. There is one possible articles supporting this:

  • “The combined use of enterococci and fungal proteases showed a decrease of the gluten concentration of more than 98% during long-time fermentation.” [2009]

No Prepared Foods

  • “Unfortunately, gluten has proven to be toxic for a proportion of people that in the last few decades has been constantly rising (Rubio-Tapia et al., 2009). Indeed, the wheat varieties that contain the most detrimental type of gluten have become more common (van den Broeck et al., 2010). This is particularly worrying given that gluten is not only naturally present in bread, cake, pasta, pizza, and beer, but it is—for its binding and thickening properties—also added to an impressive variety of other products. A survey of Australian supermarkets found gluten in nearly 2,000 different food items, ranging from sauces to processed meats, and over 100 non-foods, from pain relievers to shampoos (Atchison et al., 2010). Yet gluten triggers some action as soon as it turns up in the gut—not only in a few sensitive people, but in all of us.” [2016]  – Thus avoid all prepared foods, especially baby foods….  made from scratch may be the best path.

Summary of Bacteria Shifts

The results are not consistent across studies. The table below show the shift reported.  Some items are in both list. My general conclusion is that general lactobacillus probiotics should be avoided, but a few select one are suggested.

The increase of diversity suggests that evil strains of lactobacillus and bifidobacteria have populated. These strains may be evil solely because they do not process gluten.

With Glutten /Celiac Issues
Increase Decrease
Bacteroides Akkermansia muciniphila
Actinobacteria Bacteroides-Prevotella
Atopobium Bifidobacterium
bacterial diversity Bifidobacterium adolescentis
Bacteroides-Prevotella Bifidobacterium bifidum 
Bifidobacterium Bifidobacterium catenulatum
Bifidobacterium adolescentis Bifidobacterium lactis
Bifidobacterium Bifidum Bifidobacterium diversity
Bifidobacterium breve Clostridium coccoides
Bifidobacterium dentium Deinicoccus-Thermus
Clostridium Haemophilus spp.
Clostridium histolyticum Lactobacillus casei
Clostridium lituseburense Lactobacillus paracasei
Enterococcus, Lactobacillus Rhamnosus
Escherichia coli Lactobacillus sakei
Eubacterium rectale-Clostridium coccoides Lactobacillus zeae
Faecalibacterium prausnitzii Lactobacillus 
Firmicutes Lactobacillus-Bifidobacterium/Bacteroides-Prevotellaratio RATIO
Fusobacteria Neisseria spp.
Lactobacillus Porphyromonas
Lactobacillus Brevis Proteobacteria
Lactobacillus curvatus Proteobacteria
Lactobacillus delbrueckii bulgaricus Staphylococcus 
Lactobacillus frementum Staphylococcus-Micrococcus
Lactobacillus gasseri
Lactobacillus paracasei
Lactobacillus plantarium
Lactobacillus Rhamnosus
Lactobacillus Rossiae
Lactobacillus and Bifidobacterium groups greater diversity
Leuconostoc carnosum
Leuconostoc mesenteroides
Methylobacterium spp.
Mycobacterium spp.
Staphylococcus
sulfate-reducing bacteria

Neem – Azadirachta indica

Neem and Tulsi were two herbs that I identified from pubmed literature in 2011, based on what was published then. They fitted the profile that I was looking for to correct the bacteria shift as I understood it then. Some people have reported significant improvement from taking them.  It is time to update to the current knowledge about it:

  • “Indigenous uses of Azadirachta indica A. juss (Maliaceae) (locally known as neem) leaves in different parts of India for curing gastrointestinal disorder such as diarrhea and cholera is wide spread…The results obtained in this study give some scientific support to the uses of neem employed by the indigenous people in India employed for the treatment of diarrhea and dreadful disease cholera.” [2007]
  • Azadirachta indica mitigates behavioral impairments, oxidative damage, histological alterations and apoptosis in focal cerebral ischemia-reperfusion model of rats[2013] “Our data revealed that ASE has potent antioxidant and anti-apoptotic properties, and may be explored for its active constituents against neurodegenerative diseases.”
  • Decoction of leaves is taken for digestive and gastric problems[2015]
  • “The antibacterial activity of an ethylacetate neem cake extract (NCE) against bacteria that affect meat quality, namely Campylobacter jejuni, Carnobacterium spp., Lactobacillus curvatus, Lactobacillus sakei and Leuconostoc sp., is reported.” [2015]
  • Effect of neem (Azadirachta indica A. Juss) leaf extract on resistant Staphylococcus aureus biofilm formation and Schistosoma mansoni worms[2015]. “Neem leaf ethanolic extract presented inhibitory effect on MRSA biofilm and planktonic aggregation formation, and anthelmintic activity against S. mansoni worms.”
  • “Among various extracts, only ethanolic extract of Azadirachta indica …  were found to have potentially promising activity against test microorganisms..On the whole ethanolic extracts exhibited maximum antimicrobial effect than their corresponding aqueous and n-hexane extracts, when compared with standard antibiotics i.e., Streptomycin and Tetracycline..” [2014]
  • Leaf extract of Azadirachta indica (neem): a potential antibiofilm agent for Pseudomonas aeruginosa [2013].
  • In vitro antiviral activity of neem (Azardirachta indica L.) bark extract against herpes simplex virus type-1 infection [2010]. “These findings open a potential new avenue for the development of NBE as a novel antiherpetic microbicide.”
  • “A. indica showed strong activity against tested bacterial strains… six bacterial strains–Pseudomonas testosteroni, Staphylococcus epidermidis, Klebsiella pneumoniae, Bacillus subtilis, Proteus morganii, Micrococcus flavus.” [2007]
  • ” Azadirachta indica (bark)…exhibited a bactericidal effect against M. smegmatis” [2007]
  • “There was a clear indication that both tablet suspensions from the leaf and bark possess antimalarial activity and a suspension from the former is relatively more effective than the bark.” [2003]
  • ” an aqueous extract of Azadirachta indica stem bark was shown to enhance the immune response of BALB/C mice to sheep red blood cells in vivo.” [1999]
  • “Azadirachta indica (stem bark and leaves), and Spilanthes mauritiana (roots and flowers) were tested against 105 strains of bacteria from seven genera (Staphylococcus, Enterococcus, Pseudomonas, Escherichia, Klebsiella, Salmonella, Mycobacterium). The minimum inhibitory concentration reached by 50% (MIC50%) and 90% (MIC90) of the strains for the extracts of E. abyssinica, T. spinosa, X. caffra, and A. indica (stem bark) ranged from 0.13-8 mg/ml and from 0.5 to > 8 mg/ml, respectively. T..It is concluded that plant extracts with low MIC and MBC values may serve as sources for compounds with therapeutic potency.” [1998]
  • “It is concluded that these plants contain compounds with antimicrobial activity against H. pylori.” [1996]
  • “These data suggest that Neem stick extract can reduce the ability of some streptococci to colonize tooth surfaces.” [1996]

Bottom Line

Neem is effective against a very wide range of bacteria – from H. Pylori to Vibrio cholerae (Cholera). For myself, I went up to 8 “00” capsules per day of organic Neem and Tulsi powder (purchased in bulk and making my own capsules). Both Neem and Tulsi have been used a very long time in Asia for digestive issues.

 

Side Note:

I spotted this ranking, obtaining these (and verifying they are safe to use) would not be easy….

“, the most effective 10 plants against uropathogens could be arranged in decreasing order as follows: C. tora > A. acuminata > Schleichera oleosa > Pterocarpus santalinus > Eugenia jambolana > Bridelia retusa > Mimusops elengi > Stereospermum kunthianum > Tectona grandis > Anthocephalus cadamba.” [2013]