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● Vous avez reçu récemment une information vous présentant le nouveau service de Business Intelligence que propose maintenant BioPharmAnalyses.

● Nous vous présentons aujourd’hui un nouvel exemple des outils dédiés que nous pouvons mettre à votre disposition.

● Avec « Trend Chart On Microbiota », vous accédez rapidement à une sélection des principales informations business et scientifiques dans le domaine du microbiote.

● BioPharmarnalyses met à votre service ses outils dédiés et son expertise de l'actualité et des données scientifiques, industrielles et réglementaires pour vous accompagner dans les décisions stratégiques pour l’évolution de votre Entreprise. ●

● N’hésitez pas à nous contacter pour échanger sur vos besoins spécifiques, sur la nécessité d’évaluer un environnement concurrentiel ou toute autre demande à laquelle notre expertise est en mesure de répondre (suivi de panels de sociétés sélectionnées par vos soins, suivi de portefeuilles de produits dans une aire thérapeutique ou une pathologie donnée, panorama d’une pathologie….).

Bonne lecture

Anne-Lise Berthier
Directrice de BioPharmanalyses
(alb@biopharmanalyses.fr - 06 86 68 32 20)

contents

March 2018, 19th
BASIC SCIENCE ● Early-life exposure to low-dose oxidants can increase longevity via microbiome remodelling in Drosophila DYSBIOSIS ● Polystyrene microplastics induce gut microbiota dysbiosis and hepatic lipid metabolism disorder in mice. ● Neuroinflammation, Gut Microbiome, and Alzheimer’s Disease HOMEOSTASIS - THERAPY ● Modulation of inflammatory arthritis by gut microbiota through mucosal inflammation and autoantibody generation ● Gut microbiota and its implications in small bowel transplantation CLINICAL TRIALS ● Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium ● MaaT Pharma launches European clinical trial in severe acute Graft-versus-Host Disease INDUSTRIAL LANDSCAPE - AGREEMENTS ● Mybiotics licenses to Ferring technology using bacterial flora to treat female diseases ● Valbiotis announces results showing that LpD64 acts on alterations of the microbiota involved in the development of obesity

March 2018, 19th

BASIC SCIENCE
● Early-life exposure to low-dose oxidants can increase longevity via microbiome remodelling in Drosophila

DYSBIOSIS

● Polystyrene microplastics induce gut microbiota dysbiosis and hepatic lipid metabolism disorder in mice.
● Neuroinflammation, Gut Microbiome, and Alzheimer’s Disease

HOMEOSTASIS - THERAPY

● Modulation of inflammatory arthritis by gut microbiota through mucosal inflammation and autoantibody generation
● Gut microbiota and its implications in small bowel transplantation

CLINICAL TRIALS

● Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium

● MaaT Pharma launches European clinical trial in severe acute Graft-versus-Host Disease

INDUSTRIAL LANDSCAPE - AGREEMENTS

● Mybiotics licenses to Ferring technology using bacterial flora to treat female diseases
● Valbiotis announces results showing that LpD64 acts on alterations of the microbiota involved in the development of obesity

BASIC SCIENCE

Early-life exposure to low-dose oxidants can increase longevity via microbiome remodelling in Drosophila

Environmental stresses experienced during development exert many long-term effects upon health and disease. For example, chemical oxidants or genetic perturbations that induce low levels of reactive oxygen species can extend lifespan in several species. In some cases, the beneficial effects of low-dose oxidants are attributed to adaptive protective mechanisms such as mitohormesis, which involve long-term increases in the expression of stress response genes. Japanese and British researchers have recently shown in Drosophila that transient exposure to low concentrations of oxidants during development leads to an extension of adult lifespan. Surprisingly, this depends upon oxidants acting in an antibiotic-like manner to selectively deplete the microbiome of Acetobacter proteobacteria. They demonstrate that the presence of Acetobacter species, such as A. aceti , in the indigenous microbiota increases age-related gut dysfunction and shortens lifespan. This study demonstrates that low-dose oxidant exposure during early life can extend lifespan via microbiome remodelling rather than mitohormesis.
The results appeared in March 07th online issue of Nat Comm .

Related Informations / Publications

- Genome Res . 2018 Mar 1. pii: gr.233940.117. Selective maternal seeding and environment shape the human gut microbiome. Korpela K et al. European Molecular Biology Laboratory, Heidelberg, Germany.
Link: Abstract , Full Text
- Anal Chem. 2018 Feb 20;90(4):2475-2483. Strategy for an Association Study of the Intestinal Microbiome and Brain Metabolome Across the Lifespan of Rats. Chen T et al. Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China.
Link: Abstract

DYSBIOSIS

Polystyrene microplastics induce gut microbiota dysbiosis and hepatic lipid metabolism disorder in mice

Microplastic (MP) has become a concerning global environmental problem. It is toxic to aquatic organisms and can spread through the food chain to ultimately pose a threat to humans. In the environment, MP can interact with microbes and act as a microbial habitat. However, effects of polystyrene MP on the gut microbiota in mammals remain unclear. Here, male mice were exposed to two different sizes of polystyrene MP for 5 weeks to explore its effect. We observed that oral exposure to 1000 μg/L of 0.5 and 50 μm polystyrene MP decreased the body, liver and lipid weights in mice. Mucus secretion in the gut decreased in both sizes of polystyrene MP-treated groups. Regarding the gut microbiota, at the phylum level, polystyrene MP exposure decreased the relative abundances of Firmicutes and α-Proteobacteria in the feces. Furthermore, high throughput sequencing of the V3-V4 region of the 16S rRNA gene revealed significant changes in the richness and diversity of the gut microbiota in the cecums of polystyrene MP-treated mice. At the genus level, a total of 6 and 8 types of bacteria changed in the 0.5 and 50 μm polystyrene MP-treated groups, respectively.
The results appeared in March 09th online issue of Sci Total Env.

Related Informations / Publications

-Environ Pollut . 2018 Apr;235:322-329. Polystyrene microplastics induce microbiota dysbiosis and inflammation in the gut of adult zebrafishJin Y et al. Zhejiang University of Technology, Hangzhou 310032, China. Results / Comments : The findings suggest that polystyrene MP could induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.
Link: Abstract
- Diabetes . 2017 Aug;66(8):2137-2143. Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia. Zhu A et al. College of Life Sciences, Sichuan University, Chengdu, China.
esults /Comments : The results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis.
Link: Abstract

Neuroinflammation, Gut Microbiome, and Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that develops insidiously and causes dementia finally. There are also clinical complications in advanced dementia, such as eating problems, infections, which will lead to the decline of patients’ life quality, and the rising cost of care for AD to our society. AD will be important public health challenge. Early detection of AD may be a key issue to prevent, delay, and stop the disease. Gut microbiome and neuroinflammation are closely related with nervous system diseases, although the specific mechanism is not clear. A recent review introduces the relationship between neuroinflammation, gut microbiome, and AD. The review appeared in March 09th online issue of Mol Neurobiol .

Related Informations / Publications

-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
-Nat Commun. 2017 Jun 20;8(1):24. Intestinal microbial dysbiosis aggravates the progression of Alzheimer's disease in DrosophilaWu Sc et al. National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan
Results / Comments : the authors offer in vivo evidence from a Drosophila model that supports a role for gut microbiota in modulating the progression of Alzheimer's disease
Link: Abstract – Full Text

HOMEOSTASIS - THERAPY

Modulation of inflammatory arthritis by gut microbiota through mucosal inflammation and autoantibody generation

Significant dysbiosis and mucosal inflammation occurred early in collagen-induced arthritis (CIA), prior to visible arthritis, and continued to evolve during the course of disease. Depletion of the microbiota prior to the induction of CIA resulted in ~40% reduction in disease severity and significantly reduced serum inflammatory cytokines and anti-CII antibodies. In intestinal tissue, IL-17A and IL-22 production were delayed. Unexpectedly, microbial depletion during the late phase of CIA resulted in >90% decrease in disease severity. Anti-CII antibodies were mildly reduced, but significantly impaired in their ability to activate complement likely due to altered glycosylation profiles. These data support a model in which intestinal dysbiosis triggers mucosal immune responses that stimulate T and B cells that are key for the development of inflammatory arthritis.
The results appeared in March 13th online issue of Arthritis Rheumatol .

Related Informations / Publications

-Atherosclerosis . 2018 Mar 2;271:203-213. The gut microbiome and elevated cardiovascular risk in obesity and autoimmunity. Kasselman LJ et al. NYU Winthrop Hospital, Mineola, NY, USA.
Results / Comments : This review will discuss obesity, T1DM, RA, and SLE in the context of how each unique microbiome profile contributes to elevated cardiovascular risk.
Link: Abstract
- Obes Rev . 2018 Feb 9. doi: 10.1111/obr.12671. Microbiome-based mechanisms hypothesized to initiate obesity-associated rheumatoid arthritis. Luo Y, Blackledge WC. West China Hospital, Sichuan University, Chengdu, China
Link: Abstract

Gut microbiota and its implications in small bowel transplantation

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, the authors focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. They also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, they explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT.
The review appeared in March 09th online issue of Front Med

Related Informations / Publications

-Front Physio l. 2017 Dec 19;8:1064. Modulation of Intestinal Microbiome Prevents Intestinal Ischemic Injury. Bertacco A et al. Yale University, New Haven, CT, United States.
Results / Comments : Lactate's protective effect against intestinal ischemia due to microbial conversion to butyrate suggests possible applications in the transplant setting for reducing ischemic injury and ameliorating intestinal preservation during transport.
Link: Abstract – Full Text

CLINICAL TRIALS

Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium

Meconium is formed before birth and may reflect the microbiome of the fetus. To test our hypothesis, we investigated whether maternal factors during pregnancy, such as biodiversity of the living environment, influence the microbiome of the first stool more than immediate perinatal factors. Researchers recruited 218 consecutive newborn infants from one hospital. Regions of the bacterial 16S rRNA gene were sequenced to characterize the microbiomes of the first-pass meconium samples (N=212). They used a multivariate model to determine both the prenatal and perinatal factors affecting the microbiome. The number of operational taxonomic units ranged from zero to 448 per newborn. The most abundant phyla were Firmicutes, with a relative abundance of 44%, Proteobacteria, 28%, and Bacteroidetes, 15%. By a multivariate analysis, the biodiversity of the home environment increased the diversity of microbiomes, whereas perinatal factors such as the delivery mode or exposure to antimicrobials during labor did not have an effect.
The results appeared in March 14th online issue of Pediatr Res .

Related Informations / Publications

- Pediatrics. 2018 Mar 8. pii: e20172437. doi: 10.1542/peds.2017-2437. The Role of the Microbiome in the Developmental Origins of Health and Disease. Stiemsma LT, Michels KB. University of California, Los Angeles, USA. Link: Abstract
-Front Microbiol . 2018 Feb 20;9:270. doi: 10.3389/fmicb.2018.00270. Comparison of Meconium DNA Extraction Methods for Use in Microbiome Studies. Stinson LF, Keelan JA, Payne MS. The University of Western Australia, Perth, WA, Australia.
Results/Comments : Choice of extraction kit greatly impacts on the ability to extract and detect bacterial DNA in meconium and on the microbiome community structure generated from the samples
Link: Abstract – Full Text

MaaT Pharma launches European clinical trial in severe acute Graft-versus-Host Disease

MaaT Pharma , a clinical-stage biopharmaceutical company, said on March 06th that it has received authorization from competent authorities to launch its phase II prospective multicenter clinical trial in France. This clinical trial is planned to be extended rapidly to Germany, Poland and Italy. Acute Graft-versus-Host Disease is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), occurring in about one out of two patients, and consists of an immunologically mediated inflammatory reaction of donor immune effector cells against host cells. MaaT013 is targeting aGvHD, a clinico-pathological syndrome that usually occurs within the first month post HSCT and generally involves three organs: skin (>80% of patients with GvHD), gastrointestinal tract (50-55%) and liver (20%). Any one or any combination of these organs may be affected. More than 60% of aGvHD patients fail to have a durable response following corticosteroid therapy leading to a one-year death rate of 70-80% in this corticosteroid -refractory population. Acute GvHD is considered a rare disease with c. 10 000 cases per year in Europe and in the USA, yet about 35% to 50% of HSCT recipients will develop aGvHD1. For further info

Related Informations / Publications

-Nat Rev Cancer. 2018 Feb 16. doi: 10.1038/nrc.2018.10. Gut microbiota injury in allogeneic haematopoietic stem cell transplantation. Shono Y et al. Memorial Sloan Kettering Cancer Center, New York, New York, USA
Link: Abstract
- J Exp Med . 2017 Dec 4;214(12):3507-3518. R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease. Hayase E et al. Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Results / Comments : Administration of R-Spo1 or recombinant α-defensin prevents GVHD-mediated dysbiosis. Link: Abstract

INDUSTRIAL LANDSCAPE AND
AGREEMENTS

Mybiotics licenses to Ferring technology using bacterial flora to treat female diseases

Mybiotics said on March 13th that it has signed an agreement with Ferring Holding to license the use of its MyCrobe technology, aimed at developing bacteria that benefit women’s health. MyCrobe has developed bacterial fermentation techniques based on the study of interactions between intestinal and central nervous system, and specifically on how bacterial flora influences interactions between those systems. Early studies on this topic have stressed the effects of bacterial flora on disorders such as autism, depression and obesity; additionally, they have proven that “good” bacteria have fairly low resistance to pathogens and other adverse events. Mybiotics’ scientists are using MyCrobe to introduce “good” and highly resistant bacteria into the intestine through food supplements or modified food. For further info

Related Informations / Publications

-FEB 2018. Ferring Pharmaceuticals and MSD Announce Completion of Largest Clinical Trial Ever Conducted in Postpartum Haemorrhage
Link: Press Release

● Valbiotis announces results showing that LpD64 acts on alterations of the microbiota involved in the development of obesity

Valbiotis , a company that specializes in developing innovative nutrition solutions designed to prevent cardiometabolic diseases and provide nutritional support for patients, announced on Macrh 06th that it has proven a significant effect of LpD64 on the gut microbiota disorders involved in the development of obesity, in murine models. This effect is linked to an improvement of metabolic parameters. All of these selected results are being presented at the International Keystone Symposium "Manipulation of the Gut Microbiota for Metabolic Health" on March 6, 2018 in Banff (Canada)
For further info

Related Informations / Publications

-FEB 2018: Valbiotis announces the completion of Phase I/II clinical study recruitment for VAL-070, a product to reduce a cardiovascular risk factor.
Results / Comments: The VAL-070 candidate aims to reduce lipid profile abnormalities, which are risk factors for cardiovascular diseases.
Link : Press Release
-JAN 2018: Valbiotis announces a significant effect of VALEDIA® on the microbiota imbalances associated with metabolic diseases (preclinical)
Link: Press Release
- Diabetologia . 2018 Mar 3. doi: 10.1007/s00125-018-4583-5. Loss of angiopoietin-like 4 (ANGPTL4) in mice with diet-induced obesity uncouples visceral obesity from glucose intolerance partly via the gut microbiota. Janssen AWF et al. Wageningen University, Stippeneng 4, 6708 WE, Wageningen, the Netherlands.
Link : Abstrac t

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