The Microbiome Edition

 EDITO

As we turn the page of 2016, we, at MaaT Pharma – a microbiome–based biotech revolutionizing and shaping individualized therapies to treat serious diseases linked to dysbioses (gut microbiota imbalances)-, want to wish you a happy and healthy new year! 

2016 was an exciting year for us as we opened the first GMP compliant European Fecal Microbiota Transfer Platform and also started three clinical studies -including one dedicated to Acute Leukemia Myeloid- with renowned French medical centers.

Looking ahead, 2017 is going to be as intense as the previous years when it comes to microbiome and Fecal Microbiota Transfer and this is why we created bi-monthly updates of the gut microbiota and FMT worlds to keep you informed on the latest news!

So, enjoy this 1st edition of our newsletter dedicated to this superorganism that is man and its microbiome and let’s meet here again in March!

Thank you and have a good read,

Hervé Affagard, CEO of MaaT Pharma

 Microbiome, its role, alterations and possible treatments 

This is probably a surprise for many: we are mostly microbes. Indeed, bacteria alone outnumber our human cells. The majority live in our gastrointestinal tract (GI), particularly in the large intestine. Those microbes form an ecosystem, the microbiota, formerly called microflora, with its own genome called Microbiome.

Did you know? 

$600+ millions raised in 2016 for microbiome research

Role of the microbiome

The bacteria in our microbiota protect against other pathogenic bacteria, interact permanently with our immune system and our brain, play a role in our metabolism, and produce vitamins like vitamin B12, thiamine and riboflavin, and Vitamin K.

Increasing scientific evidence has identified human gut microbiome as a key biological interface between human genetics and environmental conditions influenced by several factors like nutrition, lifestyle, antibiotics intake, and other iatrogenic effects of medical treatments like cancer chemotherapy.

A healthy (or rich) microbiome composition and bacterial diversity is required for a number of physiological functions, human development, and immunity.

Although a causal role is not always clear, alteration and reduced bacterial diversity has been related to different health conditions such as obesity, diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, and immune-related and inflammatory diseases.

Joël Doré, Research Director at INRA, describes the concentration of bacteria along the digestive tract

As discussed above, the microbiota differs in numbers in the various compartments of the digestive tract. It also differs in composition and each compartment can be seen as a specific ecological niche harboring a specific cocktail of adapted microbes. Transit is a key regulator of microbial populations and this explains why bacteria remain below 10 million per milliliter of content until the end of the small intestine and increase dramatically in the colon from 1 to 100 billion per milliliter. They also contribute different functions, interacting with the immune system primarily in the small intestine while they contribute to the degradation of dietary fibers and supply of beneficial products in the colon.

Treatments

Research in the field moves at a breathtaking pace and has made a compelling case for the therapeutic potential of Live Biotherapeutic Products (LBPs) and of manipulating the gut microbiome.

The type of LBP approaches under development range from ecosystem-level interventions that completely reset a subject’s microbiota, as in the case of Fecal Microbiota Transfer (FMT), to interventions based on single bioactives produced by microbes. In between lie a range of treatments, from those containing defined sets of live microorganisms to those containing single microbial agents.

What is Microbiome Dysbiosis?

The alteration of microbial diversity in the gut results in a shift away from a healthy state. This is referred to as a state of Dysbiosis and can be the sign of an alteration of symbiosis (beneficial interaction) with our microbiome.

LBP approaches tend to deliver multiple answers to expand microbiota diversity, thus helping to correct Dysbiosis and thereby restore symbiosis.

FMT could be allogenic (from a donor to a recipient) or autologous (from the patient to himself)

As of today, the therapeutic approach that demonstrated the highest efficacy is still the FMT that is the most dramatic manipulation of gut microbiome composition.

Clinical work with FMT goes all the way back to the 1950s. Academic data generated to date indicate FMT leads to implantation of a new gut microbial community, and an increase in the ability of some patients to resist re-infection with agents like Clostridium difficile.

“Fecal Microbiota Transfer (FMT) is the most exciting breakthrough I have seen in medicine for years”, said Pr. Antonio Gasbarrini, Professor of Gastroenterology Catholic University of Rome Italy and also one of the FMT early adopters in Europe. “We use it to treat patients suffering from recurrent Clostridium difficile infection and we have had no death in 3 years at Gemelli, I’ve never seen such an improvement before” / This is such a powerful treatment that is now saving life.”

Most studies exploring FMT have focused on treatment of C. difficile infection (CDI).

Several factors help explain this emphasis. First, the role of microbiome alterations in driving pathology in CDI is unambiguous. Second, CDI has become epidemic in the United States. Third, from a practical and regulatory standpoint, a familiarity has built up with the use of FMT in CDI. Published case reports of FMT use in CDI have accumulated over 50 years, making it easier for investigators to obtain institutional review board approval for their experimental protocols.

Today, FMT is assessed in illnesses and conditions ranging from Obesity, Type II diabetes, PCOS, IBD, cardiovascular disorders,….

MaaT Pharma entered the clinics using an emerging strategy: autologous FMT. It proposes a therapeutic application for patients suffering from leukemia and bone & joint infections, whose major treatments induce dysbiosis and its related clinical complications. Autologous FMT consists in a transfer of the patient’s own intestinal content to himself. The objective is to fully restore the initial symbiosis (in place before the treatment).

Of course this strategy fits very well with planned interventions (massive antibiotherapy, chemotherapy, scheduled surgery, etc.) and presents major advantages in terms of safety as well as matching very well with host. This practice allows the reestablishment of the patient’s homeostasis for functions that depend on the microbiota: immune, metabolic and neuromodulatory.

Looking forward, FMT is also considered for other indications: “Possible use of FMT in the clinical practice, such as IBD, IBS, metabolic disorders, pediatrics is also considered. However, we are still missing evidence as it is for Clostridium difficile. While FMT seems very promising more research is needed as well as standardization of the processing of the samples” explains Pr. Gasbarrini.

Each of the approaches to modulating the microbiome mentioned above has its merits. 

Given the enormous potential of the field to human health, the pace of scientific progress in the use of the Microbiome as a therapy will continue to follow an ascending trend.

From symbiosis to dysbiosis

Quote of the month

“The microbiota differs in numbers in the various compartments of the digestive tract. It also differs in composition and each compartment can be seen as a specific ecological niche harboring a specific cocktail of adapted microbes. They also contribute different functions, interacting with the immune system primarily in the small intestine while they contribute to the degradation of dietary fibers and supply of beneficial products in the colon. “ Joël Doré, Scientific Advisor for MaaT Pharma

Now that we have dived into in the microbiome and how high-dose antibiotic therapies and chemotherapies can alter its balances, our March newsletter will entirely be dedicated on addressing clinical consequences of iatrogenic dysbiosis using autologous and allogeneic FMT.

So stay tuned and feel free to share any feedback and inputs on these newly launched bi-monthly updates!

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.

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