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# www.biopharmanalyses.fr ›
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BIOPHARMANALYSES
Trend Chart oN
MICROBIOTA
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contents
February 2018, 23th

HOMEOSTASIS/THERAPY 
●  Systems biology of the human microbiome
● Model of fecal transplantation predicts which bacteria will flourish
● Initial meconium microbiome in Chinese neonates delivered naturally or by cesarean section
● Host defense against oral microbiota by bone-damaging T cells
 
DYSBIOSIS
●  Endometriosis induces gut microbiota alterations in mice
●  Clostridium difficile infection: current and alternative therapeutic strategies 
● Gut microbiota trajectory in early life may predict development of celiac disease
● Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota

  INDUSTRIAL LANDSCAPE - AGREEMENTS
● Evolve BioSystems Partners With King’s College London to resolve gut dysbiosis in C-section delivered infants 
● BMS taps Sirenas for 'global microbiome' drug discovery 
 
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HOMEOSTASIS/THERAPY
Systems biology of the human microbiome 
Recent research has shown that the microbiome-a collection of microorganisms, including bacteria, fungi, and viruses, living on and in a host-are of extraordinary importance in human health, even from conception and development in the uterus. Therefore, to further our ability to diagnose disease, to predict treatment outcomes, and to identify novel therapeutics, it is essential to include microbiome and microbial metabolic biomarkers in Systems Biology investigations. In clinical studies or, more precisely, Systems Medicine approaches, investigators can use the diversity and individual characteristics of the personal microbiome to enhance our resolution for patient stratification. In a recent publication, American researchers explore several Systems Medicine approaches, including Microbiome Wide Association Studies to understand the role of the human microbiome in health and disease, with a focus on 'preventive medicine' or P4 (i.e., personalized, predictive, preventive, participatory) medicine.
The review appeared in February 13th online issue of Curr Opin Biotechnol . 
Related informations/publications
- Genome Med . 2018 Jan 29;10(1):6. Host genetic variation and its microbiome interactions within the Human Microbiome Project. Kolde R et al. Massachusetts General Hospital, 185 Cambridge St, Boston, MA, 02114, USA Link : Abstract  . Full Text
-Microbiome. 2018 Jan 26;6(1):17. Combining 16S rRNA gene variable regions enables high-resolution microbial community profiling. Fuks G et al. Weizmann Institute of Science, 7610001, Rehovot, Israel.
 Link : Astract , Full Text
Model of fecal transplantation predicts which bacteria will flourish
Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. American investigators used an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. They built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time. They found that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient.
The results appeared in February 14th online issue of Cell Host & Microbe , 
Related informations/publications
- Transpl Infect Dis . 2018 Feb 15. Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection. Woodworth MH et al. Emory University School of Medicine, USA.
Results / Comments : Preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for solid organ transplant patients.
 Link : Abstract
-Rev Esp Enferm Dig . 2018 Feb 7. Fecal microbiota transplantation in refractory or recurrent Clostridium difficile infection: a real-life experience in a non-academic center. Ponte A et al. Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal.
esults / Comments : FMT constitutes an effective and safe approach for the management of refractory and recurrent CDI, with an overall cure rate of 96% and no reported severe adverse events.
Link : Abstract  
 - Adv Exp Med Biol . 2018;1050:177-195. Faecal Microbiota Transplantation as Emerging Treatment in European Countries. Maida M et al. S.Elia - Raimondi Hospital, Caltanissetta, Italy.
Link : Abstract
Initial meconium microbiome in Chinese neonates delivered naturally or by cesarean section
Previous studies have revealed significant differences in microbiome compositions between infants delivered via cesarean section (C-section) and natural vaginal birth. However, the importance of the delivery mode in the first days of life remains unclear. Importantly, this stage is minimally affected by infant feeding. Chinese researchers recently used a metagenomic sequencing technique to characterize the meconium microbiome from the feces of a Chinese cohort of vaginally and C-section-delivered infants, including in vitro fertilization (IVF) newborns, during the first 24 h after birth. Meconium microbiome diversity was higher in vaginally delivered infants than that in C-section-delivered infants. Propionibacterium species were most abundant in the vaginally delivered infants, whereas the C-section group had high levels of Bacillus licheniformis .
The results appeared in February 19th online issue of Sci Rep  
Related informations/publications
- Front Endocrinol (Lausanne). 2017 Dec 13;8:349. Early Microbes Modify Immune System Development and Metabolic Homeostasis-The "Restaurant" Hypothesis Revisited. Nash MJ et al. University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
 Results / Comments : The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.
Link : Abstrac t, Full Text
- Genes (Basel). 2017 Dec 4;8(12). Delivery Mode and the Transition of Pioneering Gut-Microbiota Structure, Composition and Predicted Metabolic Function. Mueller NT et al. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Link : Abstract , Full Text
Host defense against oral microbiota by bone-damaging T cells
The immune system evolved to efficiently eradicate invading bacteria and terminate inflammation through balancing inflammatory and regulatory T-cell responses. In autoimmune arthritis, pathogenic TH17 cells induce bone destruction and autoimmune inflammation. However, whether a beneficial function of T-cell-induced bone damage exists is unclear. Japanese investigators have recently shown that bone-damaging T cells have a critical function in the eradication of bacteria in a mouse model of periodontitis, which is the most common infectious disease. Bacterial invasion leads to the generation of specialized TH17 cells that protect against bacteria by evoking mucosal immune responses as well as inducing bone damage, the latter of which also inhibits infection by removing the tooth. Thus, bone-damaging T cells, which may have developed to stop local infection by inducing tooth loss, function as a double-edged sword by protecting against pathogens while also inducing skeletal tissue degradation. The results appeared on February 16th online issue of Nat Comm
Related informations/publications
- Biosci Biotechnol Biochem . 2018 Feb 16:1-16. Immunomodulation by food: impact on gut immunity and immune cell function. Hachimura S et al. Graduate School of Agricultural and Life Sciences , The University of Tokyo , Japan.
Link : Abstract
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DYSBIOSIS
Endometriosis induces gut microbiota alterations in mice
Disorders in the immune system play fundamental roles in changing the intestinal microbiota. No study has used high-throughput DNA sequencing to show how endometriosis changes the gut microbiota, although endometriosis is accompanied by abnormal cytokine expression and immune cell dysfunction. A recent study includes a prospective and randomized experiment on an animal endometriosis model induced via the intraperitoneal injection of endometrial tissues. he mice were divided into endometriosis and mock groups and were sacrificed at four different time points for model confirmation and fecal sample collection. To detect gut microbiota, 16S ribosomal-RNA gene sequencing was performed. Alpha diversity was used to analyze the complexity and species diversity of the samples through six indices. Beta diversity analysis was utilized to evaluate the differences in species complexity.
The results appeared in February 15th online issue of Hum Reprod . 
Related informations/publications
- Trends Mol Med . 2018 Feb 9. Inflammasome, Inflammation, and Tissue Homeostasis. Rathinam VAK, Chan FK. UConn Health School of Medicine, Farmington, CT 06030, USA.
Results / Comments : Recent studies on the role of distinct inflammasome sensors in intestinal homeostasis are discussed.
Link : Abstract
-Int Rev Immuno l. 2018 Feb 9:1-11. Microbiota regulate the development and function of the immune cells. Yu Q et al. Beijing Normal University , Beijing , China.
 Link : Abstract
- J Vet Med Sci . 2018 Feb 8. Influence of changes in the intestinal microflora on the immune function in mice. Kishida S et al. Technology and Innovation, Kobe University, Japan.
 Link : Abstract , Full Text
Clostridium difficile infection: current and alternative therapeutic strategies
Clostridioides difficile ( C. difficile ) has become a pathogen of worldwide importance considering that epidemic strains are disseminated in hospitals of several countries, where community-acquired infections act as a constant source of new C. difficile strains into hospitals. Despite the advances in the treatment of infections, more effective therapies against C. difficile are needed but, at the same time, these therapies should be less harmful to the resident gastrointestinal microbiota. The purpose a recent review is to present a description of issues associated to C. difficile infection, a summary of current therapies and those in developmental stage, and a discussion of potential combinations that may lead to an increased efficacy of C. difficile infection treatment. The review appeared in February 21st online issue of Front Microbiol . 
Related informations/publications
- Cochrane Database Syst Rev . 2017 Dec 19. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Goldenberg JZ et al. Bastyr University Research Institute, Kenmore, WA, USA. Link : Abstract .
- Clin Pharmacol The r. 2018 Jan;103(1):102-111. Microbiota Replacement Therapies: Innovation in Gastrointestinal Care. Khanna S. Mayo Clinic, Rochester, Minnesota, USA.
 Link : Abstract . 
Gut microbiota trajectory in early life may predict development of celiac disease
In a recent study, researchers have investigated whether alterations in the developing intestinal microbiota and immune markers precede celiac disease ( CD ) onset in infants at familial risk of developing the disease. A nested case-control study was carried out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified CD. The present study includes cases of CD (n = 10) and the best-matched controls (n = 10) who did not develop the disease after 5-year follow-up. Fecal microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and immune parameters were profiled at 4 and 6 months of age and related to CD onset.
The results appeared in February 20th online issue of Microbiome  ( Abstract , Full Text )
Related informations/publications
- World J Gastroenterol. 2017 Nov 14;23(42):7505-7518. Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease. Cukrowska B et al. Medical University of Silesia, Katowice, 40-752, Poland.
 Results / Comments : The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.
 Link : Abstract , Full Text
- Front Med (Lausanne). 2017 Aug 31;4:137. De Re V et al. New Insights into the Pathogenesis of Celiac Disease. CRO Aviano National Cancer Institute, Aviano, Italy.
Results / Comments : Specific attention is paid on the last discoveries regarding the three cellular components mainly involved in the development and maintenance of CD: T-cells, B-cells, and microbioma.
Link : Abstract , Full Text
Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota
Dysbiosis of the gut microbiota has been implicated in the pathogenesis of many autoimmune conditions including type 1 diabetes ( T1D ). It is unknown whether changes in the gut microbiota observed in T1D are due to environmental drivers, genetic risk factors, or both. Australian researchers have performed an analysis of associations between the gut microbiota and T1D genetic risk using the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort. Through the analysis of five separate colonies of T1D susceptible NOD mice, they identified similarities in NOD microbiome that were independent of animal facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD microbiome. Disease-protected strains exhibited a restoration of immune regulatory pathways within the gut which could also be reestablished using IL-2 therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse. The results appeared in February 17th online issue of Microbiome  ( Abstract , Full Text ).
Related Informations / Publication
- PLoS One . 2017 Dec 6;12(12):e0188475. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study. de Groot PF et al. Academic Medical Center-University of Amsterdam, Amsterdam, the Netherlands.
Results / Comments : T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels.
 Link : Abstract , Full Text .
- Curr Diab Rep . 2017 Sep 23;17(11):105. Modulation of Type 1 Diabetes Risk by the Intestinal Microbiome. Knip M, Honkanen J. University of Helsinki, Helsinki, Finland.
Link : Abstract . 
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INDUSTRIAL LANDSCAPE
aGREEMENTS
Evolve BioSystems Partners With King’s College London to resolve gut dysbiosis in C-section delivered infants
Evolve BioSystems , a leader in advancing infant nutrition and health through restoration of the gut microbiome, announced a collaboration with King’s College London to study the effects of the probiotic EvivoTM (Bifidobacterium longum subsp. infantis ) in improving gut health in Caesarean-section delivered infants. The PROMESA study ( Pr omotion of a Healthy Gut M icrobiome in E lective Caesarean S ection A rrivals) will investigate the impact of dietary B. infantis EVC001, combined with breastfeeding, in restoring intestinal Bifidobacterium in infants delivered by Caesarean-section, a known cause of infant gut dysbiosis.
For further info
Related Informations / Publications
 -DEC 2017 : Evolve BioSystems' Activated B. infantis EVC001 Demonstrates Substantial and Persistent Remodeling of the Infant Gut Microbiome.
Link: Press Release .
BMS taps Sirenas for 'global microbiome' drug discovery
Sirenas , a biotechnology company harnessing computational approaches to discover therapeutics derived from the global microbiome, announced on February 12th that it has entered into a multi-target research collaboration agreement with Bristol-Myers Squibb to deploy Sirenas' drug discovery platform against certain undisclosed challenging therapeutic targets to identify potential drug candidates. The research collaboration leverages Sirenas' expertise in applying ATLANTIS™, its data mining technology, to identify such potential drug candidates derived from Sirenas' proprietary chemical library isolated from global microbiome collections. Under the terms of the collaboration agreement Sirenas and BMS will work together to identify such potential drug candidates. Sirenas will receive an undisclosed up-front payment, funding for research activities and potential success fees from BMS. In addition, BMS has an option to license compounds identified from the collaborative efforts under a separate agreement that will include potential milestones and royalties paid to Sirenas.
For further info . 
Related Informations / Publications
DEC 2017: Research Grant Totaling $1.68 M To Accelerate Its Drug Discovery Technology, ATLANTIS. Results /Comments: Non-dilutive funds from Bill & Melinda Gates Foundation recognizes Sirenas' novel approach to drug discovery.
 Link: PR Newswire .