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contents

June 2018, 29th

FEATURE STORY

● Human gut microbiome: hopes, threats and promises

BASIC SCIENCE

● Culturing the human microbiota and culturomics
● Communication between the microbiota and mammalian immunity

DYSBIOSIS

● Gut microbiota dysbiosis and diarrhea in kidney transplant recipients
● The gut microbiome alterations and inflammation-driven pathogenesis of Alzheimer's disease

HOMEOSTASIS - THERAPY

● The gut microbiome as a target for the treatment of type 2 diabetes
● Fecal microbial transplantation (FMT): an update

INDUSTRIAL LANDSCAPE & AGREEMENTS

● MaaT Pharma and Lutech sign licensing agreement on microbiome therapy for Graft-vs-Host Disease

● Kaleido brings in $101M in series C for its microbiome-wide therapy pipeline


June 2018, 29th

FEATURE STORY

Human gut microbiome: hopes, threats and promises

The microbiome has received increasing attention over the last 15 years. Although gut microbes have been explored for several decades, investigations of the role of microorganisms that reside in the human gut has attracted much attention beyond classical infectious diseases. For example, numerous studies have reported changes in the gut microbiota during not only obesity, diabetes, and liver diseases but also cancer and even neurodegenerative diseases. The human gut microbiota is viewed as a potential source of novel therapeutics. Between 2013 and 2017, the number of publications focusing on the gut microbiota was, remarkably, 12 900, which represents four-fifths of the total number of publications over the last 40 years that investigated this topic. A recent review discusses recent evidence of the impact of the gut microbiota on metabolic disorders and focus on selected key mechanisms. This review also aims to provide a critical analysis of the current knowledge in this field, identify putative key issues or problems and discuss misinterpretations.
The review appeared in June 22nd online issue of Gut .

Related Informations/Publications

- Trends Neurosci . 2018 Jul;41(7):413-414. Linking the Gut Microbiota to a Brain Neurotransmitter. Jameson KG et al. University of California at Los Angeles, Los Angeles, CA 90095, USA
Link : Abstract
- Mol Syst Biol. 2018 Jun 21;14(6):e8157. Deciphering microbial interactions in synthetic human gut microbiome communities. Venturelli OS et al. University of Wisconsin-Madison, Madison, WI, USA Results / Comments: Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions
Link: Abstract . Full Text

BASIC SCIENCE

Culturing the human microbiota and culturomics

The gut microbiota has an important role in the maintenance of human health and in disease pathogenesis. This importance was realized through the advent of omics technologies and their application to improve our knowledge of the gut microbial ecosystem. In particular, the use of metagenomics has revealed the diversity of the gut microbiota, but it has also highlighted that the majority of bacteria in the gut remain uncultured. Culturomics was developped to culture and identify unknown bacteria that inhabit the human gut as a part of the rebirth of culture techniques in microbiology. Consisting of multiple culture conditions combined with the rapid identification of bacteria, the culturomic approach has enabled the culture of hundreds of new microorganisms that are associated with humans, providing exciting new perspectives on host-bacteria relationships.
The review appeared in June 24th online issue of Nat Rev Microbiol .

Related Informations / Publications

¬ Sci Rep . 2017 Dec 1;7(1):16788. Culturomics and Amplicon-based Metagenomic Approaches for the Study of Fungal Population in Human Gut Microbiota. Hamad I et al. IHU Méditerranée Infection, Marseille, France
Results / Comments : Combining both culturomic and amplicon-based metagenomic approaches may be a novel strategy towards analyzing fungal compositions in the human gut
Link : Abstract – Full Text

Communication between the microbiota and mammalian immunity

Mammalian immune systems evolved within a diverse world dominated by microbes, making interactions between these two life-forms inevitable. Adaptive immunity protects against microbes through antigen-specific responses. In classical studies, these responses were investigated in the context of pathogenicity; however, we now know that they have significant effects on our resident microbes. In turn, microbes employ an arsenal of mechanisms to influence development and specificity of host immunity. Understanding these complex reactions will be necessary to develop microbiota-based strategies to prevent or treat disease.
The review appeared in June 21st online issue of Annu Rev Microbio l.

Related Informations / Publications

- Immunity. 2018 Jun 19;48(6):1072-1074. What Came First: The Microbiota or the Tr(egg) Cells? Gefen T et al. Israel Institute of Technology, 1 Efron St. Bat Galim, Haifa, 3525433, Israel
Link: Abstract
- Front Immunol. 2018 May 22;9:1018. Role of Microbiota in Sexually Dimorphic Immunity. Elderman M et al. University Medical Centre Groningen, Groningen, Netherlands
Results / Comments: Future studies should focus on a causal relationship between sexually dimorphic immunity and microbiota, considering the abovementioned interfering confounding factors
Link : Abstract – Full Text
- Crit Rev Food Sci Nutr . 2018 Jun 6:1-37. Early-Life Food Nutrition, Microbiota Maturation and Immune Development Shape Life-Long Health. Zhou X et al. Shanghai Institute of Technology , Shanghai , China
Results / Comments: The combined interrelationship between food ingredients nutrition, intestinal microbiota configurations and host system immunity provides new therapeutic targets to treat various kinds of pathogenic inflammations and chronic diseases
Link: Abstract

DYSBIOSIS

Gut microbiota dysbiosis and diarrhea in kidney transplant recipients

Post-transplant diarrhea is associated with kidney allograft failure and death but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether post-transplant diarrhea is associated with gut dysbiosis. American researchers enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S rRNA gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with post-transplant diarrhea than in 112 fecal specimens from 46 recipients without post-transplant diarrhea. They found lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted p value ≤ 0.15) in the diarrheal fecal specimens including the same 4 genera identified in their prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed PCR assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies.
The results appeared in June 19th online issue of Am J Transplant

Related Informations / Publications

- Microbiome . 2018 May 25;6(1):96. Gut microbes contribute to variation in solid organ transplant outcomes in mice. McIntosh CM et al. The University of Chicago, Chicago, USA
Results / Comments: The results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes
Link: Abstract – Full Text
- Sci Rep . 2017 Aug 31;7(1):10277. Impact of Immunosuppression on the Metagenomic Composition of the Intestinal Microbiome: a Systems Biology Approach to Post-Transplant Diabetes. Bhat M et al. University Health Network, Toronto, Canada
Link: Abstract – Full Text

The gut microbiome alterations and inflammation-driven pathogenesis of Alzheimer's disease

One of the most important scientific discoveries of recent years was the disclosure that the intestinal microflora takes part in bidirectional communication between the gut and the brain. Scientists suggest that human gut microflora may even act as the "second brain" and be responsible for neurodegenerative disorders like Alzheimer's disease ( AD ). Although human-associated microbial communities are generally stable, they can be altered by common human actions and experiences. Enteric bacteria, commensal, and pathogenic microorganisms, may have a major impact on immune system, brain development, and behavior, as they are able to produce several neurotransmitters and neuromodulators like serotonin, kynurenine, catecholamine, etc., as well as amyloids. However, brain destructive mechanisms, that can lead to dementia and AD, start with the intestinal microbiome dysbiosis, development of local and systemic inflammation, and dysregulation of the gut-brain axis.
The review appeared in June 23rd online issue of Mol Neurobiol .

Related Informations / Publications

- Crit Rev Food Sci Nutr . 2018 Jun 5:1-39. Impact of gut microbiota on neurological diseases: Diet composition and novel treatments. Larroya-García A et al. University of Murcia , Murcia, Spain
Link: Abstract
- Exp Neurobiol . 2017 Dec;26(6):369-379. Metagenome Analysis of Bodily Microbiota in a Mouse Model of Alzheimer Disease Using Bacteria-derived Membrane Vesicles in Blood. Park JY et al. Ewha Womans University, Seoul 03760, Korea
Link: Abstract – Full Text

HOMEOSTASIS - THERAPY

The gut microbiome as a target for the treatment of type 2 diabetes

Experiments in animal and human studies have produced growing evidence for the causality of the gut microbiome in developing obesity and Type 2 Diabetes . The introduction of high-throughput sequencing technologies has provided novel insight into the interpersonal differences in microbiome composition and function. The intestinal microbiota is known to be associated with metabolic syndrome and related comorbidities. Associated diseases including obesity, T2D, and fatty liver disease ( NAFLD/NASH ,) all seem to be linked to altered microbial composition; however, causality has not been proven yet. Elucidating the potential causal and personalized role of the human gut microbiota in obesity and T2D is highly prioritized.
The review appeared in June 21st online issue of Curr Diab Rep. ( Abstract - Full Text )

Related Informations / Publications

- Diabetes Metab Res Rev . 2018 Jun 21:e3043. Gut microbiome in type 1 diabetes: A comprehensive review. Zheng P et al. Central South University, Changsha, Hunan, China
Results / Comments: This review summarizes the current etiological and mechanism studies of gut microbiome in T1D
Link: Abstract
- Diabetologia . 2018 May 12. doi: 10.1007/s00125-018-4632-0. Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes. Houghton D et al. Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
Link: Abstract
- Endocrine . 2018 May 2. doi: 10.1007/s12020-018-1605-5. Microbiota and metabolic diseases. Pascale A et al. University of Pavia, 27100, Pavia, Italy
Link : Abstract

Fecal microbial transplantation: an update

Although fecal microbial transplantation is an accepted treatment for recurrent Clostridium difficile infection ( CDI ), recently it is also gaining acceptance for the treatment of refractory CDI. FMT is showing promise in ulcerative colitis and is experimental in many other conditions. The optimal practical aspects to enhance the success of FMT are still being established. The implication of current research is that the indications of FMT may be extended to other conditions in the future.
The review appeared in June 22nd online issue of Curr Opin Clin Nutr Metab Care

Related Informations / Publications

- Curr Gastroenterol Rep . 2018 Jun 9;20(7):30. Technical Aspects of Fecal Microbial Transplantation. Bhutiani N et al. University of Louisville, Louisville, KY, USA
Results / Comments: This review aims to review donor and patient selection for FMT as well as procedural aspects of FMT to help guide clinical practice
Link : Abstract
-PeerJ. 2018 May 30;6:e4663. Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children. Fareed S et al. Morehouse School of Medicine, Atlanta, GA, USA
Link: Abstract – Full Text

INDUSTRIAL LANDSCAPE
& agreements

MaaT Pharma and Lutech sign licensing agreement on microbiome therapy for Graft-vs-Host Disease

Maat Pharma SA, of Lyon, France, and Satt Lutech , a Paris-based private technology transfer company holding the exclusive rights to the scientific findings from various research groups, disclosed on June 21st a licensing agreement under which Maat will receive worldwide exclusive rights for the therapeutic application of allogeneic fecal microbiome transplants to treat acute graft-vs-host disease ( GVHD ) in patients following stem cell transplantation. The technology is based on research performed within the Clinical Hematology Department at Saint-Antoine Hospital and Sorbonne University. The license builds the foundation for Maat’s Maat-013 program, for which the company recently received authorization from the French regulatory authorities to launch a multicenter phase II study in acute GVHD. Terms were not disclosed.
For further information

Related Informations / Publications

-MAR 2018 : MaaT Pharma Launches European Clinical Trial in Severe Acute Graft-versus-Host Disease for patients receiving allogeneic Hematopoietic Stem Cell Transplantation
Link: Press Release
- J Clin Invest . 2018 May 1;128(5):1919-1936. Recipient mucosal-associated invariant T cells control GVHD within the colon. Varelias A et al. QIMR Berghofer Medical Research Institute, Brisbane, Australia
Link: Abstract
- Blood Adv . 2018 Apr 10;2(7):745-753. Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. DeFilipp Z et al. Massachusetts General Hospital, Boston, MA, USA
Results / Comments: The results indicate that empiric third-party FMT after allo-HCT appears to be feasible, safe, and associated with expansion of recipient microbiome diversity
Link: Abstract – Full Text

Kaleido brings in $101M in series C for its microbiome-wide therapy pipeline

Kaleido Biosciences , a clinical-stage healthcare company leading the development of novel chemistries to drive functions of the microbiome organ, announced on June 25th that it has closed $101 million in an oversubscribed Series C financing. Several new investors participated in the financing, including a wholly-owned subsidiary of the Abu Dhabi Investment Authority (ADIA), Fidelity Management and Research Company, Invus.
For further information

Related Informations / Publications

-OCT 2017 : Kaleido Biosciences and CoreBiome Partner to Accelerate Microbiome Therapeutic Development Results / Comments: Under the terms of this agreement, Kaleido has committed that over the next 12 months, CoreBiome will conduct its proprietary BoosterShot shotgun sequencing service on tens of thousands of microbiome samples from Kaleido’s recently completed and ongoing clinical studies.
Link: Press Release

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