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Stool substitute transplant therapy for the eradication of Clostridium difficile infection

Waverunner

Senior Member
Messages
1,079
Bob pointed me towards this topic but I'm not sure if he meant the same study. There seems to be a new lab made synthetic probiotic. I hope Bob can find out the name of it and post it here.

http://www.microbiomejournal.com/content/1/1/3

Background
Fecal bacteriotherapy (‘stool transplant’) can be effective in treating recurrent Clostridium difficileinfection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent C. difficile infection that had failed repeated standard antibiotics. Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon. Pre-treatment and post-treatment stool samples were analyzed by 16 S rRNA gene sequencing using the Ion Torrent platform.

Results
Both patients were infected with the hyper virulent C. difficile strain, ribotype 078. Following stool substitute treatment, each patient reverted to their normal bowel pattern within 2 to 3 days and remained symptom-free at 6 months. The analysis demonstrated that rRNA sequences found in the stool substitute were rare in the pre-treatment stool samples but constituted over 25% of the sequences up to 6 months after treatment.

Conclusion
This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture.

Trial registration
Clinical trial registration number: CinicalTrials.gov NCT01372943
 

Bob

Senior Member
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16,455
Location
England (south coast)
I'll just post my earlier post here, from another thread, in case anyone is interested...

There are a number of interesting research projects, developing what they call "synthetic stools", whereby they have isolated quite a number of bacteria from healthy people's guts, and have grown the bacteria in a lab, and are now testing the product on C-Difficile patients, in the form of an oral capsule. (This is intended to replace the need for fecal transplants.)
(The synthetic stools are in white powder form, rather than brown-goo form, so that's an improvement on presentation!)
They have had some success treating C-difficile patients.

From what I've read, I expect some of these synthetic stools to be approved by the FDA sometime soon (months, or perhaps a bit longer?)
I can't remember all the details, and I haven't saved all the links where I've read about it.
But I can find the name of one of the products, if anyone is interested.

If these synthetic stools are approved for treating C-difficile, then I reckon they'll soon be tested on IBS patients and various other autoimmune patients, including ME patients with gut problems.
 

Bob

Senior Member
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16,455
Location
England (south coast)
Seres SER 109

This is the synthetic stool (in development) that I've been reading about, but there are others...
I can't find all the interesting articles that I've read, but a google search for "Seres SER 109" will throw up lots of interesting reading.

I think I even found a list of the bacteria that they've isolated, and are using in the product, or that might have been for another similar product. It was an interesting list, partly because I'd never heard of the vast majority of the bacteria, if any. If I find the list, i'll post it.
 
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Waverunner

Senior Member
Messages
1,079
Thanks a lot, Bob. The pipeline of Seres Health can be found here:

http://sereshealth.com/pipeline/product_pipeline/

It seems, that they start a big trial at the end of 2014. Do you think it could become available in 2015?

Btw. it's just crazy, how much innovation is going on in the microbiome field. I truly hope, that these companies are not destroyed by regulation and can make profits before they go bankrupt.

http://thepowerofpoop.com/resources/innovation/

There are over 25 companies working in this field. Some examples:

Symbiotic Health, Inc.
According to this article published in the US publication, “The Atlantic” on December 2, 2013, a biotechnology start up, Symbiotic Health, is working towards developing FMT capsules.

The founder of Symbiotic, Gerard Honig, describes Symbiotic Health as follows “Symbiotic Health leverages the power of microbial communities to treat dangerous infections that are caused by imbalance in gut bacteria ecosystem. We aim to produce effective, low-cost therapeutics to provide patients and health care providers with practical, powerful tools to re-establish healthy gut homeostasis.”

Repoopulate
Repoopulate is an artificial fecal product that includes 33 species of the bacteria in the colon. It was developed at the University of Guelph, located in Ontario, Canada. It is not yet commercially available and has been used twice to treat C. difficile. The treatment was successful in both patients treated.

Vedanta
This company was created by Puretech Ventures, a venture capital company. According to the company website, the mission of the company is “Vedanta Biosciences mission is to develop a novel class of therapies that modulate pathways of interaction between the human microbiome and the host immune system. Vedanta was co-founded by Puretech Ventures and a group of renowned experts in immunology and microbiology.”

Vedanta has created its first drug, VE-202. VE-202 is essentially a mixture of different strains of live bacteria packed into a pill that would be ingested and make its way into the gut, where the bacteria would colonize the intestine, and stimulate the immune system in a specific way. Vedanta’s plan is to initially test that drug as a treatment for inflammatory bowel disease, where Olle (Dr. Bernat Olle is one of Puretech Ventures principals) says there is the strongest amount of evidence that shows alterations in the microbiome lead to disease symptoms. Read more here here and here.

In June 2013, Johnson & Johnson’s venture unit backed Vedanta Biosciences. Read about it here and here.

Seres Health
Seres Health is a clinical stage biotherapeutic company focused on discovering and developing Ecobiotic™ therapeutic products to treat important diseases by targeting the underlying biology of the human microbiome. Seres Healths’ lead Ecobiotic, SER-109, is currently in the clinic for the treatment of Clostridium difficile infection (CDI). An early stage clinical trial has shown efficacy of SER-109 for the treatment of CDI. Seres Health is developing Ecobiotics across a range of other therapeutic areas including metabolic and inflammatory conditions.

ViThera Pharmaceuticals
ViThera Pharmaceuticals is an early stage biotech company located in Cambridge, MA. ViThera scientists harness the synthetic potential of bacteria to produce therapeutic molecules within the body to develop a revolutionary new treatment for Inflammatory Bowel Disease. ViTheras’ research combines the natural benefits of probiotics with the power of synthetic biology to create game-changing, novel therapeutics for chronic diseases.
 

Bob

Senior Member
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Location
England (south coast)
It seems, that they start a big trial at the end of 2014. Do you think it could become available in 2015?
I'm not sure. Based on that timeline, I think 2015 might be optimistic. But it will depend whether they're on a phase III trial, and if it's to be classed as a medicine. And I get the feeling that the FDA tend to drag their feet about these things. (But I'm not an expert re the FDA etc.)
 

Waverunner

Senior Member
Messages
1,079
I'm not sure. Based on that timeline, I think 2015 might be optimistic. But it will depend whether they're on a phase III trial, and if it's to be classed as a medicine. And I get the feeling that the FDA tend to drag their feet about these things. (But I'm not an expert re the FDA etc.)

Yeah, that's one of the few things they are good at, dragging their feet and inhibiting innovation.

Just found this:

http://www.raps.org/regulatoryDetail.aspx?id=9081

"In June 2013, FDA quietly announced it would do away with the requirement, seeking to instead adopt "enforcement discretion" over the sector. In other words, it generally will not regulate FMT procedures, but retains the right to enforce the sector if it believes a doctor is subjecting his or her patients to harmful treatments."

If I understand this correctly, doctors are allowed to do microbiome transplants, which can contain all kinds of infections, since they come from human donors, but companies are not allowed to offer lab based FMTs.

Edit No2: At least Rebiotix is conducting a phase III trial soon.

http://medcitynews.com/2014/07/new-funding-for-next-generation-fecal-transplant-company/

"The company’s lead therapy candidate, RBX2660, was given Food and Drug Administration Fast Track status about a year ago. It is currently working with the FDA to design a Phase 3 clinical program for the drug."
 
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Bob

Senior Member
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Location
England (south coast)
Here's the list of bacteria that they've used to produces a 'synthetic stool', that I mentioned I'd come across.
But I don't think this is the Seres product (See bottom of this post for more info)...
http://www.microbiomejournal.com/content/1/1/3/table/T1



Here's some info that I had previously posted on another thread...

I'm interested in the idea of a 'synthetic stool', as they call it. (i.e. lab-refined collection of probiotic bacteria, isolated from human faeces, that can be taken in a capsule.)

The BBC article mentions it here:
BBC News said:
A different vision of the future of the treatment is a move away from faeces altogether. Instead, patients would receive a live bacterial culture targeted to fight Clostridium difficile - in effect, a synthetic stool.

Although it would be developed from faecal samples, it would only need to contain a handful of strains of bacteria, not the hundreds present in excrement, which would make its impact on the human gut more reproducible and understandable.

Trevor Lawley at the Sanger Institute in the UK is down to just 18 strains in his synthetic stool. He is in the process of overcoming a series of technical problems, such as how to grow these anaerobic organisms and prevent them from evolving before they can be used. But he says the real challenge in the emerging field of "live biotherapeutics" is how to regulate it.

Meanwhile, in Canada Dr Petrof has already cured C. diff in two patients using a synthetic solution containing 33 strains of bacteria grown inside a "robogut"- an imitation colon.

Faecal transplant, she says, works. "But I'll be the first to admit it's crude. It's essentially like pouring sewage into people." Her synthetic stool, on the other hand, smells a lot less obnoxious and is a sterile-looking milky colour.

I looked up the researchers mentioned, and found a list of the 33 strains of bacteria used to create a synthetic stool, by Dr Petrof in Canada, to treat C. Difficile:
http://www.microbiomejournal.com/content/1/1/3/table/T1

The table is taken from this paper which describes the successful treatment of two patients (who had C. Difficile) using this 'synthetic stool':
http://www.microbiomejournal.com/content/1/1/3
 
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Waverunner

Senior Member
Messages
1,079
Here's a very recent article about the Seres product:

Taking the Yuck out of Microbiome Medicine
by Carl Zimmer
http://phenomena.nationalgeographic.com/2014/08/14/taking-the-yuck-out-of-microbiome-medicine/

Very interesting. I checked the table from the robogut article. Some strains can be found in probiotics (Bifidobacterium longum, Lactobacillus casei/paracasei, Lactobacillus casei, Escherichia coli). The rest seems quite new, especially Eubacterium eligens, Eubacterium rectale and Faecalibacterium prausnitzii. I wish all the best to Dr. Petrof and that her product reaches the clinical practice soon.

It would be very interesting to know, what spores SER--109 contains but I couldn't find any information.
 

WillowJ

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WA, USA
oh, good. The FDA wanted to stop fecal transplants until it could regulate them and the GI docs treating C diff patients said no way were they going to stop using something that effective.

I'm pleased they got it into a form that doesn't require finding one's own donor and doesn't have the weird factors of the original, and doesn't need endoscopy to use (though they had, I think, a way to make coated freeze-dried swallowable pellets of the 'natural' variety). Besides the obvious benefits, this does raise the possibility of it being used to fix the gut microbiome for other conditions in addition to C diff.
 
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Bob

Senior Member
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Location
England (south coast)
Results are out for a small trial of SER-109, a synthetic stool, for treating C-difficile.

"The data presented at the 2014 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) show that in patients with recurrent CDI SER-109 resulted in clinical cures with 29 of the trial's 30 patients (97 percent) reaching the 8-week endpoint free of infection."

http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=99128#.VBA2yvmwJcR
 

Sasha

Fine, thank you
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17,863
Location
UK
Results are out for a small trial of SER-109, a synthetic stool, for treating C-difficile.

"The data presented at the 2014 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) show that in patients with recurrent CDI SER-109 resulted in clinical cures with 29 of the trial's 30 patients (97 percent) reaching the 8-week endpoint free of infection."

http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=99128#.VBA2yvmwJcR

This is good news - I think a synthetic stool is going to be much more acceptable to both patients and to the regulatory authorities than a transplanted one.