The Fecal Microbiota Transfer Edition
Today more than ever microbiota is recognized to play a key on the individual’s health. Recent studies have shown the effectiveness of Fecal Microbiota Transfer (FMT) to modulate microbiota and address specific pathologies. While FMT remains the highest efficacy demonstrated to modify the microbiota, this could be a complicated and restrictive process hence the relative scarcity of its utilization within medical centers.
That is the reason why we are determined to improve this practice and make it more reliable, simple and standardized to include it in protocols treatments concerning hematology, oncology and infectious diseases. Through our European GMP FMT Platform, we industrialised/standardised the procedure, thus gaining knowledge on safety, dose, stability, etc. and contributing to the establishment of regulatory guidelines. We also implemented our proprietary state of the art gut print™ platform to better understand underlying mechanisms. Developing the FMT emerged from our will to implement a new practice easier to operate for the medical community and a natural solution for patients.
Our team of scientists controls/ oversees the entire supply chain and is currently developing an FMT- based oral form with a marketing authorization planned before 2023. As this protocol is both new and “ancient”, we dedicated our second newsletter to allogenic and autologous FMT. These could, in the future, optimize patients’ treatment and cure diseases.
 Metagenome sequencing platform
Hervé Affagard, CEO of MaaT Pharma
FMT in modulating Gut Microbiome: Achievements and future perspectives
Fecal transplantation dates back to 4th century in China where it was intended to cure some food poisoning cases and severe diarrhea. Modern clinical work with FT goes back to the 1950s. It started with the treatment of patients with pseudomembranous enterocolitis. But for years FMT remained a rarely used therapy until the 80s when the first attempts to treat Clostridium difficile infection (CDI) were reported.
Over the last 15 years, (CDI) has become epidemic and continues to gain momentum with greater incidence, morbidity, and mortality than in decades past.
As the C. difficile epidemic continues to grow, the numbers of failed treatments and patients who experience relapses or recurrences also are increasing.
Only FMT showed to be an effective alternative intervention. Case reports and small case series to date suggest that recurrent CDI can be cured with a single treatment.
We can consider that CDI is responsible of the large spread of FMT. But recent research and evidence is accumulating to suggest that both the diversity and richness of the gut microbiota are important for health. Disturbance of the Man-Microbe equilibrium – dysbiosis – is associated and/or correlated with a variety of diseases. The most relevant example is the long-term effect of antibiotic treatments or other clinical practices.
To date the list of disorders addressed with microbiome modulation using FMT in getting longer. FMT is being actively investigated as a therapeutic strategy for many diseases, including gastrointestinal, autoimmune and metabolic disorders, obesity, metabolic syndrome, type 2 diabetes mellitus, fatty liver disease, infection with multidrug-resistant organisms, hepatic encephalopathy, and disorders of the skin, the central nervous system, Autism and pediatric allergy disorders.
There are two types of FMT:
Allogenic FMT is a promising strategy for the treatment of inflammatory diseases, especially diseases associated with microbiota dysbiosis. It involves the administration of distal gut microbiota-containing fecal material from a healthy person (donor) to a patient with an altered gut microbiota that is causing disease. The modulation of the gut microbiota by FMT primarily follows the probiotic principle, but instead of treating the patient with specific strains, a large community (600 species on average) of microorganisms is used.
Based on a recent trial the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) approved the use of Allogenic FMT for diarrhea recurrence after antibiotic-associated diarrhea.
 Zhang et al, Am J Gastroenterol 2012
Only in Europe, Inflammatory bowel disease affects about 2,5 million people for which current treatments show limits. Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic, relapsing, and remitting inflammatory diseases of the intestines that lead to significant morbidity and mortality in affected individuals. They are due to an aberrant immune response toward luminal antigens, and are also influenced by environmental factors.
An imbalanced intestinal microbiota – “dysbiosis,”- has been repeatedly observed in IBD and is now recognized as a key factor in the gut inflammatory process.
Current treatment modalities center on the modulation of the immune system and are limited by side effects, few therapeutic options, and a lack of efficacy.
FMT has gained interest as a novel treatment option in IBD.
A systematic review made on twenty clinical trials showed variable remission rates in FMT in the treatment of IBD. Only limited clinical response of circa 40% of remission, was reported certainly due to a lack of standardization.
Quote from Dr Vehreschild
“Particularly in the treatment of ulcerative colitis, using FMT, promising results have been recently published. These data suggest that specific microbial signatures contribute to long-term remission. In light of these findings, standardization of samples is becoming an issue of high clinical relevance.”
Each individual harbors a unique intestinal microbiota; therefore, the most appropriate method for restoring its symbiosis (after antibiotic or chemotherapy treatments for example) is to give it back its initial particular composition.
The only way to do so, is to prepare a representative sample of the microorganisms that make up the individual ecosystem before any given treatment. This sample becomes a source of reseeding at the end of treatment. Since the representative sample is a stool specimen, this is autologous FMT as opposed to allogeneic FMT where another donor is involved.
The major advantage of the Autologous FMT is the elimination or dramatic decrease of the risks of human-to-human transmission (viral counting, metabolic abnormality, etc.) or immunological incompatibility inherent in donor stool transplantation.
Autologous FMT strategy is best prescribed every time an intervention is foreseeable or can be anticipated (massive antibiotherapy, chemotherapy, scheduled surgery, etc.).
 Fecal Microbiota Transplantation for Inflammatory Bowel Disease – Joanna Lopez, MD, and Ari Grinspan, MD – Gastroenterology & Hepatology Volume 12, Issue 6 June 2016
Increasing antimicrobial resistance is a growing threat to human health and is notably a consequence of excessive use of antimicrobial agents in clinical medicine. A continuous rises in resistance by 2050 would lead to 10 million people dying every year. In addition to focusing on clinically relevant pathogens when monitoring levels and risks for emergence of antimicrobial resistance, it is important to also consider the role of the enormously diverse human commensal microbiota.
As of today, MDR bacteria incidence in Europe is 386 000 cases per year leading to 6.5 % death.
Autologous FMT is well designed for high risk patients of emergence of colonization and infection with multidrug-resistant bacteria during hospitalization as it makes possible the reconstitution of the intestinal microbiota, correcting the dysbiosis and eliminating the purporting of nosocomial strains. It restores to the patient all its gut barrier and also immune and metabolic abilities, which precisely depend on the ecological complexity specific to each person. It makes possible the use antibiotics without suffering from their disastrous consequences.
Quote from Dr Vehreschild
“Autologus FMT preparations collected previous to antibiotic exposure may represent a welcome alternative to allogeneic preparations. Opposed to the allogeneic setting, an autologous preparation decreases the risk of longterm side effects, triggered by interaction of the microbiota with the immune system, as well as of transmission of potential pathogens.”
MaaT Pharma’s input
The team of 20 enthusiasts comprises experienced and knowledgeable professionals are dedicated to become a leader in microbiome protection and the treatment of clinical consequences of dysbiosis. To support these two types of FMT, MaaT Pharma opened the first GMP compliant European Fecal Microbiota Transfer Platform that produced around 100 drugs today and started three clinical trials:
- ODYSSEE: Prevention of dysbiosis complications with autologous fecal microbiota transplantation in Acute Myeloid Leukemia patients undergoing intensive treatment
- ULYSSE: Epidemiological study on the clinical characteristics of intestinal dysbiosis in patients with Acute Myeloid Leukemia
- OSIRIS: A prospective clinical study aiming to assess the potential of gut microbiotherapy in patients with Bone and Joint Infections undergoing long term antibiotherapy
The technology developed by MaaT Pharma are shown their effectiveness on mice studies and now are currently testing on human through clinical trials – including one dedicated to Acute Leukemia Myeloid- with renowned French medical centers. In November 2016, MaaT Pharma announced their first positive DSMB safety review and continuation of its Phase 1b ODYSSEE study. Maat pharma has based its technology, research, and future developments not only to correct the dysbiosis, but also to restore a normal dialog between the host immune system and the microbiota which will play a key role in all settings.
As FMT and microbiota hold great promises, they both have generated a lot of interest worldwide. The regulation of FMT varies between/depending on countries. Therefore, we have decided to dedicate our next newsletter on regulation with a focus on Europe.
Hervé Affagard, CEO of MaaT Pharma
About MaaT Pharma
Founded at the end of 2014 and based in Lyon (France), MaaT Pharma (Microbiota as a Therapy) is a microbiome–based biotech company revolutionizing and shaping individualized therapies to treat serious diseases linked to dysbiosis (gut microbiota imbalances). MaaT Pharma is currently developing its first candidate using its proprietary Fecal Microbiota Transfer Platform for patients suffering from leukemia, bone and joint infections, as these harsh treatments provoke dysbiosis. MaaT Pharma’s revolutionary and rapid approach plays a considerable part in the evolution of individualized treatment therapies.