Mutaflor

[Tarmander]

I was on antibiotics a lot for strep throat as a kid, I think it was the trigger for my IBS. Thankfully I have been able to be mostly cramp free managing my diet stress levels. I am a prime example for the low residue type diets, keeping the bacteria feeding frenzy to a minimum. Thankfully sugar doesn't seem to make it further than my small intestine as Ray has suggested many times. But it is definitely an issue for some people who seem to do horrible on high fructan diets.

A while ago I tried those soil derived probiotics by garden of life and had serious herxing I never took it again! lol

You know I wonder about antibiotics and children. For a long time the generic message of the health world has been that these antibiotics hurt kids by killing off their "good" flora. But maybe it's more that antibiotics target certain strains and let other strains dominate, and these strains that dominate become unbalanced and make by products/vitamins/chemicals that unbalance the system.

The solution if that was the case would not be to avoid antibiotics, but to take a range of them and then repopulate with a wide variety of strains like Prescript Assist and Equilibrium

 

[InChristAlone]

You know I wonder about antibiotics and children. For a long time the generic message of the health world has been that these antibiotics hurt kids by killing off their "good" flora. But maybe it's more that antibiotics target certain strains and let other strains dominate, and these strains that dominate become unbalanced and make by products/vitamins/chemicals that unbalance the system.

The solution if that was the case would not be to avoid antibiotics, but to take a range of them and then repopulate with a wide variety of strains like Prescript Assist and Equilibrium

Yeah definitely allows the nastier stuff to dominate. That type of kill and repopulate protocol is something Travis Burch does with his clients now, you should have him on your podcast. I am so hesitant to try it, its the one thing I've shied away from because of experiences with probiotics in the past. I wonder if this Mutaflor would have benefits by itself.

 

[Blossom]

you should have him on your podcast.

 

[Mauritio]

Mutaflor is a very potent anti-fungal and anti-bacterial agent!
Mice pretreated with mutaflor and after that beeing given candida albicans, had 10 times lower numbers of viable candida cells.
So it seems that mutaflor makes your body able to defend itself much better against many pathogens in general, not just bacteria ( but the effect on bacteria was great as well)

From the study:

"These results suggest that E. coli strain Nissle 1917 is a potent immunostimulator of bacterial origin with highly protective efficacy against pathogenic bacterial of fungal infections."

Augmentation of host defence against bacterial and fungal infections of mice pretreated with the non-pathogenic Escherichia coli strain Nissle 1917. - PubMed - NCBI

 

[Blossom]

Mutaflor is a very potent anti-fungal and anti-bacterial agent!
Mice pretreated with mutaflor and after that beeing given candida albicans, had 10 times lower numbers of viable candida cells.
So it seems that mutaflor makes your body able to defend itself much better against many pathogens in general, not just bacteria ( but the effect on bacteria was great as well)

From the study:

"These results suggest that E. coli strain Nissle 1917 is a potent immunostimulator of bacterial origin with highly protective efficacy against pathogenic bacterial of fungal infections."

Augmentation of host defence against bacterial and fungal infections of mice pretreated with the non-pathogenic Escherichia coli strain Nissle 1917. - PubMed - NCBI

Fantastic, thank you!

 

[Mauritio]

Fantastic, thank you!

You're welcome . There's another one on mutaflor and how it acts on TLR4 ,which was really interesting . I'll post it if I should find it again.

 

[Pompadour]

If i understand this correctly, this strain of bacterias can be not so good sometimes.
Look at this study
Sensitivity to Escherichia coli Nissle 1917 in mice is dependent on environment and genetic background

 

[Tarmander]

If i understand this correctly, this strain of bacterias can be not so good sometimes.
Look at this study
Sensitivity to Escherichia coli Nissle 1917 in mice is dependent on environment and genetic background

yeah I think that was mentioned above...the potential of it to mutate. It was just in mice, but concerning.

I think its long history of use gives it quite a bit of leeway though

 

[Pompadour]

yeah I think that was mentioned above...the potential of it to mutate. It was just in mice, but concerning

No, looks like that one was another study. Here was no mutation of bacteria. Rather some kind of mice were more prone to damage of the bacteria.

 

[Tarmander]

No, looks like that one was another study. Here was no mutation of bacteria. Rather some kind of mice were more prone to damage of the bacteria.

Oh, okay gotcha. Interesting

 

[Mauritio]

No, looks like that one was another study. Here was no mutation of bacteria. Rather some kind of mice were more prone to damage of the bacteria.

Thanks for posting this study. You are rigtht ,this is a different one than the one I mentioned on the first page.
Although the bad outcomes only applie to short fraction of the mice that carry a specific mutation on the TLR4 receptor. I dont even know if this mutation exists in human, so again I doubt this is applicable to humans and if it is , only for a small fraction of them.
Its still interesting though because this mutation normally makes mice more resistent to endotoxin , so I dont know why that would be bad in this case, maybe the immun reaction is suppressed ?!

From the study:
"With the exception of C3H/HeJZtm mice, which carry a defective toll-like receptor (TLR)4-allele, no lesions were obvious in mice of different strains orally inoculated with EcN for 1 week

 

[Mauritio]

I highly reommend everyone ,who speaks german to read this publication from 1925 by Nissle himself. He writes about his years of practical use ,for example how long you should use and why that is .

https://scholar.google.com/scholar?...J:scholar.google.com/&scioq=&hl=de&as_sdt=0,5 (First link)

I will summarize some of the stuff ,but still recommend to give this a read since I cant grasp everything:

- How long you should take it is individually different, but NOT only until you dont have the symptoms anymore, sine the gut wall has not recovered from years of disease ,
-the gut microbiome is often better after only 8-14 days , if mutaflor will be ceased then , a gradual return to the old symptoms will follow
-the older and sicker the person , the longer it should be taken, he says about 3-4 months
- chronic constiapted people often need 4-5 weeks to feel improvement
- apparently other illnesses have successfully been treated including : arthritis urica, anemia and migraine
- after cessation of the therapy, the strain can stay in gut for months or even years ( longest observed time was 2 and half years! )
- also mutaflor could be taken preventative against dysentery
- the product looses some of its effects in 20 degrees Celsius even after 2 weeks, it keeps well for more than 7 years at a temperature of 4 to 6 degrees Celsius
-apparently people have been complaining about the price already in the 1920s


Bei den meisten Leiden, für die Mutaflor indiziert ist, beobachtet man, wenn die Kur gegen die Vorschrift bereits mit dem Tage der ' vollständigen Verdrängung der bisherigen Darmflora abgebrochen wird, ein schrittweises,' mehr oder minder schnelles Sinken der Wertigkeit des im Darm an gesiedelten Mutaflorstamms; er kann schließlich antagonistisch mit, dem ursprünglichen Kolistamm des Patienten übereinstimmen. und. hat dann alle schützenden und heilenden Fähigkeiten verloren. Die Erscheinung steht im Gegensatz zu den künstlichen Kulturen hoch- wertiger Kolistämme, die oft 1.-2 Jahre lang bei nur monatlicher: Ueberinjpfung (Gelatinestich) unverändert oder nahezu unverändert bleiben.

Behandelt man eine alte Kolitis, so wird sich zur Zeit der Verdrängung der bisherigen Flora, also nach etwa 8-14 Tagen, be
reits ein deutlicher Besserungserfolg zeigen, denn die Reize, welche die pathologische Darmflora durch ihre Leibessubstanz, ihre Stoffwechselprodukte und durch abnorme Gärung und Fäulnis des Darminhalts verursachte, sind dann beseitigt. Zu dieser Zeit ist aber die Darmschleimhaut, die oft jahrelang diesen Reizen aus- gesetzt war, noch nicht wiederhergestellt, weder histologisch noch physiologisch. Die Mutaflorbakterien befinden sich alo auch weiterhin in einer' vorläufig noch pathologisch veränderten Umgebung und werden dadurch ungünstig beeinflußt. Unterbricht man jetzt fehierhafterweise mit Rücksicht auf den sichtbaren Erfolg die Behandlung, so sinkt die Wertigkeit der eingepflanzten Kolibakterien allmählich so weit, daß sie der Wucherung schädlicher, zufällig mit der Nahrung einwandernder Keime keinen Widerstand mehr entgegensetzen können, und es stellt sich das Rezidiv ein

Um einem solchen Versagen vorzubeugen, muße daher die Therapie so lange fortgesetzt werden, bis auch die Darmschleimhaut wieder normal funktioniert, also geheilt ist. Da dies auf direktem Wege nicht sicher festzustellen ist, so bleibt nur übrig, die Behandlung mindestens so lang.e auszudehnen, wie si nach den praktischen' Erfahrungen bei ähnlichen Fällen, genügt, um Rezidiven vorzu- beugen. Aeltere Leiden verlangen daher auch stets eine mindestens 3-4 Monate l'ange Kur.

Diese Ueberlegungen machen es auch verständlich, warum die ersten Zeichen einer Besserung durch Mutafloranwendung bei chro- nischen Obstipationen bisweilen erst in der 4. oder gar 5. Woche bemerkbar werden können.. Hier hat der Ersatz der Darmflora durch hochwertige Kolibazillen noch nicht genügt, das Krankheitsbild zu ändern, die Wiederkehr der normalen Darmfunktion er- fordert längere Zeit, und erst dann werden die ersten Erfolge der Therapie sichtbar.

Das Mutaflor ist daher unter der Voraussetzung genügend langer, eventuell mehrmonatiger Anwen- dung auch imstande, uns beim Studium. der Patho- genese mancher Krankheiten des Darins oder auch anderer Organe wesentliche Dienste zu leisten. Es ist nicht nur praktisch wertvoll, wenn. durch Mutaflorbehandlung eine Arthritis urica oder eine- jahrzehntelang, bestehende Migräne 'mit der gleichzeitigen Kolitis zur Heilung gebracht werden, wenn es auf dem gleichen Wege gelingt, Kolipyelitiden oder Milchschorf zu beseitigen, einen Patienten mit Biermerscher Anämie, die auf der Basis einer Nahrungsmittelvergiftung entstand; so wiederherzustellen, daß er jetzt seit sechs Jahren rezidivfrei geblieben ist. Hier beweist der Heilerfoig, daß die primäre Ursache dieser Erkrankungen eine pathologisch wirkende Darmflora war. Vorsichtiger müssen in dieser Beziehung Erkrankunken beurteilt werden, die durch Mutaflor wohl gebessert, aber nicht geheilt wurden; in solchen Fälleñ ist die Möglichkeit zu berücksichtigen, daß die pathologische Darmflora erst sekundär angesiedelt wurde und nur 4as Krankheitsbild komplizierte

Einige hauptsächlich aus rein wissenschaftlichem Interesse er- folgte Nachprüfungen der Kolibakterien von Personen, die durch Mutaflor geheilt wurden, ' ließen erkennen, daß der Behandlungsstamm nicht nur Monate, sondern Jahre hindurch unverändert im Darm erhalten bleiben kann (längster beobachteter Zeitraum 21/2 Jahre nach Abschlúß der Behandlung). Wie C h i I k o ws k i (Dissertation Freiburg 1924) nachgewiesen hat, gelingt es sogar, den vOm Mensehen gewonnenen Mutaflorstamm durch Verfütterung in 'Kaninchen anzusiedeln und sie dadurch gleichzeitig zur Bildutig spezifischer, weñn auch nicht starker Agglutinine zu veranlassen. Es scheint daher nicht ausgeschlossen, daß Mutaflor auch zur Behandlung geeigneter Tierkrankheiten (z. B. Kälberruhr) herangezogen werden kann.

 

[Tarmander]

I highly reommend everyone ,who speaks german to read this publication from 1925 by Nissle himself. He writes about his years of practical use ,for example how long you should use and why that is .
Thieme - Login

I will summarize some of the staff ,but still recommend to give this a read since I cant grasp everything:
- How long you should take it is individually different, but NOT only until you dont have the problems anymore, sine the gut wall has not recovered from years of disease ,
-the gut microbiome is often better after only 8-14 days , if mutaflor will be ceased then , a gradual return to the old symptoms will follow
.- the older and sicker the person , the longer it should be taken, he says about 3-4 months
- chronic constiapted people often need 4-5 weeks to feel improvement
- apprently other illnesses have successfully been treated including : arthritis urica, anemia and migraine
- after cessation of the therapy, the strain can stay in gut for months or even years ( longest observed time was 2 and half years! )
- also mutaflor could be taken preventative against dysentery


Bei den meisten Leiden, für die Mutaflor indiziert ist, beobachtet man, wenn die Kur gegen die Vorschrift bereits mit dem Tage der ' vollständigen Verdrängung der bisherigen Darmflora abgebrochen wird, ein schrittweises,' mehr oder minder schnelles Sinken der Wertigkeit des im Darm an gesiedelten Mutaflorstamms; er kann schließlich antagonistisch mit, dem ursprünglichen Kolistamm des Patienten übereinstimmen. und. hat dann alle schützenden und heilenden Fähigkeiten verloren. Die Erscheinung steht im Gegensatz zu den künstlichen Kulturen hoch- wertiger Kolistämme, die oft 1.-2 Jahre lang bei nur monatlicher: Ueberinjpfung (Gelatinestich) unverändert oder nahezu unverändert bleiben.

Behandelt man eine alte Kolitis, so wird sich zur Zeit der Verdrängung der bisherigen Flora, also nach etwa 8-14 Tagen, be
reits ein deutlicher Besserungserfolg zeigen, denn die Reize, welche die pathologische Darmflora durch ihre Leibessubstanz, ihre Stoffwechselprodukte und durch abnorme Gärung und Fäulnis des Darminhalts verursachte, sind dann beseitigt. Zu dieser Zeit ist aber die Darmschleimhaut, die oft jahrelang diesen Reizen aus- gesetzt war, noch nicht wiederhergestellt, weder histologisch noch physiologisch. Die Mutaflorbakterien befinden sich alo auch weiterhin in einer' vorläufig noch pathologisch veränderten Umgebung und werden dadurch ungünstig beeinflußt. Unterbricht man jetzt fehierhafterweise mit Rücksicht auf den sichtbaren Erfolg die Behandlung, so sinkt die Wertigkeit der eingepflanzten Kolibakterien allmählich so weit, daß sie der Wucherung schädlicher, zufällig mit der Nahrung einwandernder Keime keinen Widerstand mehr entgegensetzen können, und es stellt sich das Rezidiv ein

Um einem solchen Versagen vorzubeugen, muße daher die Therapie so lange fortgesetzt werden, bis auch die Darmschleimhaut wieder normal funktioniert, also geheilt ist. Da dies auf direktem Wege nicht sicher festzustellen ist, so bleibt nur übrig, die Behandlung mindestens so lang.e auszudehnen, wie si nach den praktischen' Erfahrungen bei ähnlichen Fällen, genügt, um Rezidiven vorzu- beugen. Aeltere Leiden verlangen daher auch stets eine mindestens 3-4 Monate l'ange Kur.

Diese Ueberlegungen machen es auch verständlich, warum die ersten Zeichen einer Besserung durch Mutafloranwendung bei chro- nischen Obstipationen bisweilen erst in der 4. oder gar 5. Woche bemerkbar werden können.. Hier hat der Ersatz der Darmflora durch hochwertige Kolibazillen noch nicht genügt, das Krankheitsbild zu ändern, die Wiederkehr der normalen Darmfunktion er- fordert längere Zeit, und erst dann werden die ersten Erfolge der Therapie sichtbar.

Das Mutaflor ist daher unter der Voraussetzung genügend langer, eventuell mehrmonatiger Anwen- dung auch imstande, uns beim Studium. der Patho- genese mancher Krankheiten des Darins oder auch anderer Organe wesentliche Dienste zu leisten. Es ist nicht nur praktisch wertvoll, wenn. durch Mutaflorbehandlung eine Arthritis urica oder eine- jahrzehntelang, bestehende Migräne 'mit der gleichzeitigen Kolitis zur Heilung gebracht werden, wenn es auf dem gleichen Wege gelingt, Kolipyelitiden oder Milchschorf zu beseitigen, einen Patienten mit Biermerscher Anämie, die auf der Basis einer Nahrungsmittelvergiftung entstand; so wiederherzustellen, daß er jetzt seit sechs Jahren rezidivfrei geblieben ist. Hier beweist der Heilerfoig, daß die primäre Ursache dieser Erkrankungen eine pathologisch wirkende Darmflora war. Vorsichtiger müssen in dieser Beziehung Erkrankunken beurteilt werden, die durch Mutaflor wohl gebessert, aber nicht geheilt wurden; in solchen Fälleñ ist die Möglichkeit zu berücksichtigen, daß die pathologische Darmflora erst sekundär angesiedelt wurde und nur 4as Krankheitsbild komplizierte

Einige hauptsächlich aus rein wissenschaftlichem Interesse er- folgte Nachprüfungen der Kolibakterien von Personen, die durch Mutaflor geheilt wurden, ' ließen erkennen, daß der Behandlungsstamm nicht nur Monate, sondern Jahre hindurch unverändert im Darm erhalten bleiben kann (längster beobachteter Zeitraum 21/2 Jahre nach Abschlúß der Behandlung). Wie C h i I k o ws k i (Dissertation Freiburg 1924) nachgewiesen hat, gelingt es sogar, den vOm Mensehen gewonnenen Mutaflorstamm durch Verfütterung in 'Kaninchen anzusiedeln und sie dadurch gleichzeitig zur Bildutig spezifischer, weñn auch nicht starker Agglutinine zu veranlassen. Es scheint daher nicht ausgeschlossen, daß Mutaflor auch zur Behandlung geeigneter Tierkrankheiten (z. B. Kälberruhr) herangezogen werden kann.

That’s really good info thank you

 

[Mauritio]

That’s really good info thank you

No problem, man . I think there is a lot more info out there as this is one of the oldest probiotics and has been studied very much.

 

[Tarmander]

Ran across this study today: A double-blind placebo-controlled trial to study therapeutic effects of probiotic Escherichia coli Nissle 1917 in subgroups of patients with irrita... - PubMed - NCBI

Appears Mutaflor can sometimes take awhile, 10-11 weeks, before results set in for people with IBD. Especially effective for those who took antibiotics before their IBD set in.

This is basically what the CFS people are doing...taking antibiotics and then Mutaflor.

"Altogether, the responder rate was higher in the EcN than in the placebo group. However, only after 10 and 11 weeks, the differences were significant (Δ 20.0% points [95% CI 2.6; 37.4], p = 0.01 and Δ 18.3% points [95% CI 1.0; 35.7], p = 0.02, respectively). The best response was observed in the subgroup of patients with gastroenteritis or antibiotics prior to irritable bowel syndrome onset (Δ 45.7% points, p = 0.029). No significant differences were observed in any other subgroup. Both treatment groups showed similar adverse events and tolerance.

CONCLUSIONS:
Probiotic EcN shows effects in irritable bowel syndrome, especially in patients with altered enteric microflora, e.g. after gastroenterocolitis or administration of antibiotics."

 

[ecstatichamster]

Thank you all.
Thanks @Mauritio

I’m noticing this drops my temperatures when I take it. I am taking 2 twice a day. Anyone else notice it?

 

[Mauritio]

Ran across this study today: A double-blind placebo-controlled trial to study therapeutic effects of probiotic Escherichia coli Nissle 1917 in subgroups of patients with irrita... - PubMed - NCBI

Appears Mutaflor can sometimes take awhile, 10-11 weeks, before results set in for people with IBD. Especially effective for those who took antibiotics before their IBD set in.

This is basically what the CFS people are doing...taking antibiotics and then Mutaflor.

"Altogether, the responder rate was higher in the EcN than in the placebo group. However, only after 10 and 11 weeks, the differences were significant (Δ 20.0% points [95% CI 2.6; 37.4], p = 0.01 and Δ 18.3% points [95% CI 1.0; 35.7], p = 0.02, respectively). The best response was observed in the subgroup of patients with gastroenteritis or antibiotics prior to irritable bowel syndrome onset (Δ 45.7% points, p = 0.029). No significant differences were observed in any other subgroup. Both treatment groups showed similar adverse events and tolerance.

CONCLUSIONS:
Probiotic EcN shows effects in irritable bowel syndrome, especially in patients with altered enteric microflora, e.g. after gastroenterocolitis or administration of antibiotics."

Interesting, thanks for sharing. Its actually in line with what nissle himself said ( difficult cases should take 3-4 months )
I have started taking it a few days ago. Cannot yet explain the effects, but there certainly is a reaction...I plan on taking it for a longer time.

And @ecstatichamster funny you mention that. I started freezing after taking it. I am normally never cold , more uncomfortably warm ,but yesterday I was walking around with a friend of mine and i just had to go into a cafe to warm up . Also at home I notice I am more cold.
What's your explanation of that?
It might be lowering of metabolism but I also suspect it lowers blood sugar pretty strong for me ( I get the typicall symptoms) so that might be the explanation . Do you notice any change in weight?

 

[Tarmander]

This study reviews Ecoli probiotics in general:Insights from 100 Years of Research with Probiotic E. Coli

I will also put this quote here for people's reference for all the different studies out there on Mutaflor:


"E. coli Nissle
Most studies in which EcN was applied to treat human illness relate to inflammatory bowel disease (IBD). The oldest published study describing human exposure, from 1989, collected data from 1074 patients with either functional enteric disorders or IBD, who had taken EcN as recorded by their physician [28]. The study reported a tolerance in more than 90% of the patients, with initial side effects not requiring termination in 2.8%, and termination due to adverse reactions in 1.5% of the patients. Of those with functional intestinal disorders, 84% subjectively judged the treatment to be good to very good; for IBD, this was 78%. As already mentioned above, a double-blind placebo-controlled clinical trial confirmed that IBD patients indeed responded to EcN treatment, though significant improvement was only apparent after 10 to 11 weeks of treatment [24]. In this study, patients with altered enteric microbiota (e.g., after gastroenterocolitis or following the intake of antibiotics) responded best. The abovementioned observation that human β-defensins were induced in vitro and detected at 10 to 15-fold increase following EcN treatment [21] could provide a mechanistic explanation of this positive effect.

Ulcerative colitis (UC), a subcategory of IBD in which the lining of the colon is specifically affected, is typically treated with mesalazine. Already in 1997, a randomized double-blind clinical trial involving UC patients compared 12 weeks of EcN treatment with the gold standard of mesalazine treatment, showing similar start and end scores of the clinical activity index as well as similar relapse rates for both treatments [29]. These results were confirmed 2 years later by another research group [30] and again in a larger study by the research group of the 1997 study [31]. UC can lead to colorectal cancer, for which microsatellite instability in the genome is a possible driver. Rather disappointingly, a follow-up study showed that neither EcN nor mesalazine treatment could prevent the formation of such microsatellite instability in UC patients [32]. Effectiveness of EcN similar to mesalazine was also demonstrated in children between 11 and 18 years suffering from UC [33]. When acute distal UC was treated by rectal administration of EcN, it produced mixed results with no effectiveness for the intention-to-treatment population, but efficacy for the per-protocol population, resulting in dose-dependent remission rates [34]. A volunteer study with healthy individuals was performed to assess if mesalazine could be taken together with EcN, which turned out to have no effect on survival of the probiotic in stools [35]. Whether concomitant treatment with both would increase effectiveness for UC treatment has not yet been described.

In contrast to these positive findings, the effect of EcN on UC was questioned by a recent study comparing pretreatment with ciprofloxacin before EcN administration [36]: 78% of patients receiving ciprofloxacin followed by placebo reached remission, compared to 66% of those receiving EcN after ciprofloxacin. Similarly, for the group receiving placebo instead of ciprofloxacin, again those taking EcN showed lower remission than those receiving twice the placebo (54% and 86%, respectively) [36].

Crohn’s disease, another variant of IBD, is related to adherent-invasive E. coli (AIEC) colonization. It is, therefore, not surprising that treatment for this disorder is rarely tested with EcN, as probiotic products not containing E. coli are usually preferred. A meta-analysis compared all available data on probiotic treatment of CD [37] included only one study that compared EcN treatment with placebo. That study showed no statistically significant difference [38]. More recently, in vitro experiments with biopsies from CD patients and healthy controls showed that EcN lacked the capacity to compete with AIEC [39], which makes it unlikely that EcN can be effective to treat CD.

Since bloating is sometimes reported as a side effect of EcN intake, this was investigated in a randomized double-blind study with healthy volunteers [40]. EcN was well tolerated and did not significantly affect abdominal symptoms, stool frequency, or stool consistency; it had no effect on intestinal gas dynamics.

Other enteric disorders were also challenged with EcN treatment. For instance, a randomized double-blind clinical trial involved 70 patients with constipation [41]. After 4 weeks of therapy, their stool frequency had increased significantly compared with controls, confirmed by crossover patients, when verum patients were changed to placebo and vice versa. When liver cirrhosis patients were treated with EcN, they showed improved liver functions (as by Child–Pugh classification) and reduced endotoxin levels though there were no other significant improvements [42, 43] (publication in Czech). These two publications, describing data obtained from the same study, are thus far the only described application of EcN to treat liver disease.

In a prospective open trial, uncomplicated diverticular disease of the colon was treated with antimicrobials and absorbents, followed by EcN for 5 weeks, which prolonged remission time [44]. Another open trial, this time treating collagenous colitis, showed therapeutic benefit when EcN treatment lasted for at least 4 weeks [45].

Babies were also treated with EcN. In a randomized double-blind clinical trial, healthy newborns were given the bacteria during their first 5 days of life [46]. The stools were EcN-positive in >90% of infants for as long as 6 months. A variety of pathogens was shown to be absent or reduced in numbers during the study. The same group performed a randomized double-blind trial on premature infants where an increase in EcN-specific IgA antibodies could be demonstrated [47]. EcN was further shown in a double-blind randomized trial to shorten acute (viral) diarrhea in infants and toddlers with 2.3 days [48]. Finally, to complete the positive findings for various applications, a case was described of Clostridium difficile-negative pseudomembranous colitis following antimicrobial treatment in an adult, who was successfully treated with multiple intestinal lavages, followed by EcN administration [49].

Less successful was an attempt to treat subjects with hay fever (grass pollen-allergic rhinoconjunctivitis). A randomized double-blind clinical trial with 6 months of treatment covering the full exposure season did not show effects on symptoms, pollen-specific humoral IgE or IgA levels, or a skin prick test [50]. Mutaflor was also not able to reduce carriage of multidrug-resistant E. coli in elderly residents of long-term care facilities [51], though, in this study, only two out of 12 treated subjects had detectable EcN in their feces.

This latter observation brings up an interesting question: how well is EcN capable to colonize the human gut? The applied daily dose of Mutaflor is relatively high (see Table 1), and in several of the abovementioned trials, the product was taken for weeks at a time. Colonization of newborn babies was demonstrated, but in those hosts, the gut is still relatively unoccupied [46]. When seven adult volunteers were orally challenged for 1 week, EcN could only be detected in the stools of four of these [52]. The study combining EcN with mesalazine mentioned above reported that, 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]. These findings demonstrate that EcN is not very efficient to colonize the human gut long-term. Attempts to improve this colonization potential were not identified. In one animal study, the colonization properties of EcN in mice could be enhanced by introduction of a missense mutation in a histidine kinase gene, but this did not improve its capacity to outcompete enterohemorhagic E. coli challenge [53].

It has been argued that some of the effects of probiotics are caused by cellular components, so that the organisms would not be required to be alive and establish colonization in the gut [54]. Nevertheless, according to Caselli and coworkers, the definitions of probiotics used by the World Health Organization and the Food and Health Organization include that they have to “remain viable and stable after culture, manipulation, and storage before consumption (and) have to survive to gastric acid and biliary and pancreatic digestion” [55]. These authors argue that, since the host’s pattern recognition receptors (PRRs) play a pivoting role in probiotic applications, it would be irrelevant whether the bacteria were dead or alive [55]. If this argument were accepted, one can only wonder why probiotic products are based on living organisms, which are more difficult to produce, store, and quality control than preparations of cellular components. My gut feeling (pun intended) is that living organisms have more effect than dead ones, though there are few data to support one or the other view.

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The origin of E. coli Nissle 1917
The story of the origin of the Nissle 1917 strain has been told many times and even featured in the publications announcing the release of the sequenced EcN genome [56, 57]. According to this story, Alfred Nissle had isolated the strain from the stool of a First World War soldier, who was the only one of his unit not suffering from dysentery. Some citations state that the lucky soldier remained free from “diarrhea” [58] or “shigellosis” [59] while yet others mention his resistance was against typhoid fever. The original publications cited for this information vary, as Nissle was rather productive and many of his papers are still being cited. Some of the citations refer to his earliest publication, from 1916 [60] cited by, among others, Pöhlmann et al. [61], or a work from 1918 [62], cited by authors who elaborately mention that the soldier had been stationed on the Balkan peninsula [63] although this information was never described by Nissle himself. Others cite a 1925 paper [64], cited by Zyrek et al. [65] which is the oldest record in PubMed mentioning the term “Mutaflor” (though, in fact, Nissle introduced the commercial name in a footnote in a publication from 1919 [66], but that publication is not represented in PubMed). His late works are also frequently cited, e.g., a publication from 1959 [67], cited by Verna and Lucak [59] where it is reported that the soldier was protected from shigellosis, or from 1961 [68] (cited in the review article [58]), or even the posthumous publication that appeared in 1966, a year after Nissle’s death, in which the author, aged 90, had looked back at his long career [69] (cited on page 213 by Tannock [70]).

It is heart-warming to see that so many international authors still read original literature in the German language, but the various citations for this information, and the variation in description of what should be a historical consistent story, is a bit suspicious. Moreover, some of these original publications are hard to come by. I was able to retrieve five original publications written by Alfred Nissle to check what exactly he had published on Mutaflor.

His 1916 paper [60] is very informative and deserves to be summarized here in some detail. He described experiments he performed with E. coli (“Koli” as he called them) isolated from stool samples. He cultured these on agar plates (“Endoagarplatten”) and spiked them with a fixed ratio of 2:3 of “Typhusbacillen” (in later experiments, he cultured the mixture in a broth for 6 or 7 h before plating). On the plates, he observed that some, but not all, of the tested E. coli isolates could inhibit or reduce the growth of what we now call Salmonella enterica serovar Typhi. He called this phenomenon “antagonism” and expressed the number of “Typhus” colonies per 100 “Koli”-colonies as the “antagonistic index” of the assessed E. coli isolate. He then compared this index between strains, describing in detail the difficulty in standardizing the test, performed with inclusion of control strains with a proven high or low antagonistic index. At the extremes, he observed that the strongest antagonistic strains were 1350 times better able to inhibit S. Typhi growth than the weakest tested isolates.

Nissle tried to explain the observed differences in antagonism by differences in lactic acid production, but observed there was no correlation, nor was indole production related. He further reported that strongly antagonistic strains not only inhibited S. Typhi but also “Paratyphus-Dysenterie”, “Kruse-Shiga”, “Dysenterie Flexner”, and “Proteus”. These old names refer to Salmonella enterica serovar Paratyphi, Shigella dysenteriae, Shigella flexneri, and either Proteus vulgaris or P. mirabilis (neither of which are strongly pathogenic but that was not known at that time). He was even able to show antagonism between different E. coli strains, by clever use of a strain that was unable to produce gas on a medium containing glucose (“Traubenzucker”, his strain was an atypical non-gas-former, as have subsequently been characterized and described [71]). This indicator strain was defeated by strong antagonistic E. coli strains but not by weakly antagonistic ones. Nissle further showed that the antagonistic property was lost after heating at 60 °C, which we now know is indicative of proteins or peptides. The phenotype he determined was most probably the result of microcins; it is now known that EcN produces microcins MccM and MccH47 [72].

When he compared E. coli strains obtained from 15 fecal samples of healthy individuals, three were very strong, five were strong, four were medium, and three were weakly antagonistic (it is unclear whether these experiments were performed with the indicator E. coli or with Typhus). In contrast, 25 strains from “pathological stools” produced two reasonably strong, five medium, and 18 weak antagonists. From these observations, Nissle concluded that a strong antagonistic E. coli in the gut might protect against enteric diseases.

The three “very strong” antagonistic strains from healthy stool were described in a bit more detail. One was found by chance, but the other two came from selected individuals: Nissle had visited an army hospital (“Verwundeten-Lazarett”) and had specifically selected patients who reported to have never suffered from enteric diseases, even though they had been exposed to acutely infected patients. He identified two such persons (it was not described why they were hospitalized or where they had served) who produced E. coli with an antagonistic index of 100:10 and 100:3, respectively.

Nissle had no means to conserve his strains other than by subculture. He describes that one of his precious strong antagonizers lost its phenotype after 2 years. He was able to protect the other two, one isolated in March 1915 and the other in September of that year (unclear is, whether both of these were the isolates from the soldiers), from that fate by storing them in capsules made of paraffin or wax. To test their positive effect against infections, he first gave these capsules to healthy volunteers and, after proven safety, to diseased patients. The rest of the 1916 publication describes successful treatments of 11 cases. Case 11 suffered from Typhus infection from 25 July till 8 August 1915 and shed high numbers of “Typhusbacillen” since (from 12 September till 17 April 1916) when treatment was started. The person shed low numbers till 28 April. after which Thypus bacteria could no longer be detected in his stool. The treatment consisted of 52 capsules of “Kolireinkultur” administered in 37 days. Nissle described that the person produced the administered high-antagonistic E. coli in his stool 3 weeks after termination of treatmen (at least he was able to isolate a strain with similar antagonistic properties from the stool). Nissle suggested the capsules as treatment for acute intestinal infections and speculated it might even be effective against other infections, giving the example of diphtheria. The 1916 publication demonstrates the extraordinary scientific skills of Nissle. Not only was he a sharp observer, he also designed his experiments under standardized conditions with inclusion of the necessary controls, tested explanatory hypotheses and discarded these based on experimental evidence, developed means to store his biological material, and performed clinical trials avant la lettre.

In his 1918 publication [62], Nissle continued his investigations with the capsules that were from then on commercially produced under the name “Mutaflor,” though it remains unclear whether the E. coli strain used in the product was his isolate from March or September 1915. Who the individual was from whose stool it was isolated, whether it was one of the soldiers, and if so, where he had been stationed is not disclosed by Nissle. What we can deduc from the literature is that the strain was originally isolated in 1915, possibly from a soldier of unknown nationality, who at that time was treated in a German army hospital. The year “1917” that has become part of the name of this strain present in Mutaflor neither refers to the year of isolation, nor to the year the strain was first publicly described."

 

[ecstatichamster]

I’m taking 2 capsules twice per day. I may try to spread them out more evenly. I’m doing that because the product info mentions for constipation that may be a good dose so that’ s what I’m doing.

I will say that although it’s for the opposite direction (from diarrhea to good BMs), S. Boulardii has been the only probiotic I’ve ever taken (and still occasionally take) that has a profound and immediate effect with zero harm and only good. We kept a dog alive with it because it is the only cure for diarrhea that I’ve ever seen that works when nothing else does.

All to say that I hope this EcN is as good...even if not as quick acting.

 

[Tarmander]

Interesting, thanks for sharing. Its actually in line with what nissle himself said ( difficult cases should take 3-4 months )
I have started taking it a few days ago. Cannot yet explain the effects, but there certainly is a reaction...I plan on taking it for a longer time.

And @ecstatichamster funny you mention that. I started freezing after taking it. I am normally never cold , more uncomfortably warm ,but yesterday I was walking around with a friend of mine and i just had to go into a cafe to warm up . Also at home I notice I am more cold.
What's your explanation of that?
It might be lowering of metabolism but I also suspect it lowers blood sugar pretty strong for me ( I get the typicall symptoms) so that might be the explanation . Do you notice any change in weight?

Interesting @ecstatichamster ...I have not noticed a drop in temp or a lowering of blood sugar...

I did notice a loosening of stools, however I am taking a decent amount of magnesium right now and that could be it.

The only thing I really notice so far is just better sleep.