Category Archives: Microbiome/Microbiota Information

Microbiota Restoration Therapy (MRT) (Drug Platform) Reduces Antibiotic-resistant Bacteria Gut Colonization In Patients with Recurrent C. difficile Infection (rCDI)

Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study

Abstract

Background

Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.

Methods

An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.

Results

Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.

Conclusions

Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.

Trial registration

ClinicalTrials.gov, NCT01925417; registered on August 19, 2013.

 

To read the article in its entirety – please click on the following link to be redirected:

https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00843-9#citeas

Seres Therapeutics and Nestle’ Health Science Team Up For the Joint Commercialization of Seres Therapeutics Investigational Microbiome Treatment for Recurrent C. difficile Infection (rCDI)

Seres Therapeutics and Nestlé Health Science have announced a decision to team up for the joint commercialization of Seres’s investigational oral microbiome treatment for recurrent Clostridioides difficile (C. difficile) infections (CDI).

Nestlé Health Science had previously received commercial rights to Seres’s therapeutics for inflammatory bowel disease and CDI, but only outside the U.S. and Canada. This expansion places Nestlé as Seres’s global collaborator for SER-109, a therapy the company hopes to treat a leading contributor to hospital-acquired infections in North America. If approved by the U.S. Food and Drug Administration (FDA), the agent, dubbed SER-109, will be the first microbiome therapeutic available.

Each year, CDI contributes to the deaths of 20,000 Americans. Standard of care for recurrent CDI includes the use of fecal microbial transplants. Currently, there is no microbiome therapies approved for any indications, which has created an unmet need recognized by an ever-growing list of pharmaceutical companies partnering with microbiome startups.

Seres’s investigational SER-109 includes purified Firmicutes spores; the rationale for including these spores is “based on their modulatory role in the life cycle of C. difficile and disease pathogenesis,” according to a statement made by the company.

Findings from the pivotal Phase III ECOSPOR III trial announced back in August 2020 showed SER-109 significantly reduced the CDI recurrence rate compared with placebo over an eight-week period. The absolute reduction of the CDI recurrence rate was 27% while the relative risk reduction was 68%. In addition, up to 88% of patients experienced a sustained clinical response by the end of the eight weeks.

Nestlé Health Science has agreed to use Aimmune Therapeutics, the company’s global pharmaceutical business, to lead the commercialization of the therapy. In return, Seres has agreed to receive upfront licensing payments totaling $175 million. An additional $125 million will be paid to Seres by Nestlé upon FDA approval of the microbiome agent.

Under terms of the agreement, Seres holds the sole responsibility for costs associated with development and pre-commercialization of SER-109 in the U.S. The company will be eligible to receive up to 50% of the commercial profits once the therapeutic is commercialized.

“Nestlé Health Science has been a terrific collaborator in our quest to develop a new treatment option for patients suffering from recurrent C. difficile infection, and their support over the past few years has been critical in advancing SER-109 to address this unmet need,” said Eric Shaff, Seres Therapeutics’ chief executive officer, in a statement. “As we prepare for potential approval and commercialization, we are eager to embark side-by-side on our next phase with a company that believes as fervently as we do in the potential of this transformative approach to reduce the recurrence of CDI.”

Nestlé Health Science’s CEO, Greg Behar, added that the company “is focused on the fast-developing areas of gut health, food allergies and metabolic health within our global pharmaceutical business, Aimmune Therapeutics.” As such, Aimmune’s “fully integrated commercial infrastructure” will be leveraged to launch the therapy, pending approval.

Seres has been busy this year in moving its investigational microbiome therapy pipeline in front of the FDA. Last month, Seres announced the agency had cleared an Investigational New Drug application for the company’s other investigational microbiome therapeutic for preventing antibiotic-resistant bacterial infections as well as graft-versus-host disease.

The company is advancing SER-155 into a Phase Ib trial under a collaboration with Memorial Sloan Kettering Cancer Center. “SER-155 represents a novel microbiome technology with the potential to address antibiotic-resistant bacterial bloodstream infections and further to modulate host immunomodulatory responses to decrease graft-versus-host disease,” said Seres’s chief scientific officer, Matthew Henn, Ph.D., in a statement.

 

SOURCE:  https://www.biospace.com/article/seres-nestle-agree-to-jointly-commercialize-microbiome-agent-for-c-diff-infections/

Racing the Tract app Is An Educational Game For All Ages

 

 

 

 

Created by Teena Chopra, MD, MPH

Racing The Tract

Available on Apple Store

‎Educational, fun, and free! Welcome to Racing the Tract, a fun and educational game that teaches you how to maintain a healthy Gut Microbiome by making healthy diet and lifestyle choices, and answering trivia questions. Make it to the end of the race track by gaining good bacteria points.

Cost:  FREE

 

CDI and Recurrence; Microbiome – Based Therapy Publication

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

To read the article in its entirety, please download the .pdf format below

2021-MicrobiomeBasedTherapyCDI

 

 

Cornell Researchers Develop Tool To Create Maps Of the Locations and Identify Different Microbial Species Including Those That Make Up the Gut Microbiome

Cornell researchers developed an imaging tool to create intricate spatial maps of the locations and identities of hundreds of different microbial species, such as those that make up the gut microbiome. The tool will help scientists understand how complex communities of microorganisms interact with each other and also their environment, which is to say, us.

WHAT MICROBES ARE IN YOUR GUT AND WHERE?

The team’s paper, “Highly Multiplexed Spatial Mapping of Microbial Communities,” published Dec. 2 in Nature. The paper’s lead author is doctoral student Hao Shi, M.Eng. ’18.

Resource:  https://phys.org/news/2020-12-spatial-view-gut-microbiome.html

“There are communities of bacteria that live in our bodies and play an important role in human health and biology, and there’s a rich diversity of these microbes. We know this from technologies such as DNA sequencing that create lists of the bacterial species that are present in a community,” said Iwijn De Vlaminck, the Robert N. Noyce Assistant Professor in Life Science and Technology in the Meinig School of Biomedical Engineering, and the paper’s senior author.

“However, there are very limited tools to understand the spatial interactions between these microbes, and those are quite clearly important to understand the metabolism of these communities, and also how these microbes interact with their host,” he said.

De Vlaminck and Shi set out to create their imaging method by using a two-step process called high phylogenetic resolution microbiome mapping by fluorescence in situ hybridization (HiPR-FISH). They collaborated with the labs of co-authors Warren Zipfel, associate professor of biomedical engineering, and Ilana Brito, assistant professor and the Mong Family Sesquicentennial Faculty Fellow in Biomedical Engineering, to incorporate additional imaging and microbiome expertise.

To locate the microbial communities, the researchers designed oligonucleotide probes that target specific bacteria cells based on the presence of a signature gene sequence, 16S ribosomal RNA, and they made another group of probes that label the cells with fluorophores. Then the team used confocal microscopy to light up the fluorescent markers with lasers, and they used machine learning and custom software to decode the fluorescence spectra and interpret the images, resulting in an efficient and cost-effective technology with single-cell resolution.

The researchers created the palette for their spatial maps with a mixture of 10 basic colors that could “paint” a total of 1,023 possible color combinations of E. coli, each fluorescently labeled with a unique binary barcode.

“The imaging itself leads to very beautiful, rich images with all bacterial cells in different colors,” De Vlaminck said. “But to allow the quantitative understanding of microbe interactions, the distances between cells, cluster sizes and so on, you need to be able to interpret these in an automated way by a computer so that you can convert this image into a digitized representation of the community.”

The team applied their technology to two different systems: the gut microbiome in mice and the human oral plaque microbiome. In the case of the , they were able to demonstrate how the spatial associations between different bacteria are disrupted by antibiotic treatment.

Spatial mapping could be an important tool for studying and possibly treating a range of diseases in which bacteria are a major culprit, such as inflammatory bowel disease, colorectal cancer, and infection.

“We’d like to dig deeper into the biology of systems where microbiomes play important roles and try to understand how these kinds of spatial dynamics change when you have a disease in progression,” Shi said. “We want to see if that offers any clues and therapeutic insights that we can harness to help people.”