Tag Archives: Human Microbiome

Study shows Microbiome Differences Between Intensive Care Unit Patients Hospitalized From Healthy Patients



The microbiome of patients admitted to the intensive care unit (ICU) at a hospital differs dramatically from that of healthy patients, according to a new study published in mSphere.


Researchers analyzing microbial taxa in ICU patients’ guts, mouth and skin reported finding dysbiosis, or a bacterial imbalance, that worsened during a patient’s stay in the hospital. Compared to healthy people, ICU patients had depleted populations of commensal, health-promoting microbes and higher counts of bacterial taxa with pathogenic strains – leaving patients vulnerable to hospital-acquired infections that may lead to sepsis, organ failure and potentially death.

What is dysbiosis?  Pathogens, antibiotic use, diet, inflammation, and other forces can cause dysbiosis, a disruption in these microbial ecosystems that can lead to or perpetuate disease  (1)

What makes a gut microbiome healthy or not remains poorly defined in the field. Nonetheless, researchers suspect that critical illness requiring a stay in the ICU is associated with the the loss of bacteria that help keep a person healthy. The new study, which prospectively monitored and tracked changes in bacterial makeup, delivers evidence for that hypothesis.
“The results were what we feared them to be,” says study leader Paul Wischmeyer, an anesthesiologist at the University of Colorado School of Medicine. “We saw a massive depletion of normal, health-promoting species.”
Wischmeyer, who will move to Duke University in the fall, runs a lab that focuses on nutrition-related interventions to improve outcomes for critically ill patients.

He notes that treatments used in the ICU – including courses of powerful antibiotics, medicines to sustain blood pressure, and lack of nutrition – can reduce the population of known healthy bacteria. An understanding of how those changes affect patient outcomes could guide the development of targeted interventions to restore bacterial balance, which in turn could reduce the risk of infection by dangerous pathogens.
Previous studies have tracked microbiome changes in individual or small numbers of critically ill patients, but Wischmeyer and his collaborators analyzed skin, stool, and oral samples from 115 ICU patients across four hospitals in the United States and Canada. They analyzed bacterial populations in the samples twice – once 48 hours after admission, and again after 10 days in the ICU (or when the patient was discharged). They also recorded what the patients ate, what treatments patients received, and what infections patients incurred.
The researchers compared their data to data collected from a healthy subset of people who participated in the American Gut project dataset. (American Gut is a crowd-sourced project aimed at characterizing the human microbiome by the Rob Knight Lab at the University of California San Diego.) They reported that samples from ICU patients showed lower levels of Firmicutes and Bacteroidetes bacteria, two of the largest groups of microbes in the gut, and higher abundances of Proteobacteria, which include many pathogens.
Wischmeyer was surprised by how quickly the microbiome changed in the patients. “We saw the rapid rise of organisms clearly associated with disease,” he says. “In some cases, those organisms became 95 percent of the entire gut flora – all made up of one pathogenic taxa – within days of admission to the ICU. That was really striking.” Notably, the researchers reported that some of the patient microbiomes, even at the time of admission, resembled the microbiomes of corpses. “That happened in more people than we would like to have seen,” he says.
Wischmeyer suggests the microbiome could be tracked like other vital signs and could potentially be used to identify patient problems and risks before they become symptomatic. In addition, now that researchers have begun to understand how the microbiome changes in the ICU, Wischmeyer says the next step is to use the data to identify therapies – perhaps including probiotics – to restore a healthy bacterial balance to patients.
Everyone who collaborated on the project – including dietitians, pharmacists, statisticians, critical care physicians, and computer scientists – participated on a largely voluntary basis without significant funding to explore the role of the microbiome in ICU medicine, says Wischmeyer.


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(1)  http://www.serestherapeutics.com


Vedanta Biosciences Raised $50 Million With Plans To Advance Precise Cocktails Of Bacteria Into Clinical Testing




Vedanta Biosciences of Cambridge, MA, has raised $50 million with plans to take advance a number of drugs—precise cocktails of bacteria—into clinical testing.

Formed by company creator PureTech Health six years ago,

Vedanta is trying to understand the relationship between the microbiome and human disease.

The quest to understand the human microbiome has been picking up steam. In Washington, the Obama administration just launched the $121 million Microbiome Initiative, adding to a string of high-profile initiatives in cancer, brain research, and precision medicine. And microbiome drugs are making their way into testing.

The most advanced candidate, SER-109 from Seres Health, is in mid-stage trials for a dangerous gastrointestinal infection called clostridium difficile (C. diff). Data should come this quarter.

These therapies have several different forms. Enterome and Second Genome are developing small molecule drugs to modify the way bacteria interact with their host’s gut. Synlogic and EnBiotix are genetically engineering bacteria. Vedanta and Seres pack strains of bacteria into a pill.

Other than Seres’s C. difficile treatment and a follow-on drug for ulcerative colitis, all of these efforts are preclinical.

But Vedanta CEO and PureTech vice president Bernat Olle views SER-109 as just the beginning for microbiome drugs.

“Clinically it’s been very successful and it’s helped bring the field a lot of attention that otherwise wouldn’t have been received, but I’ve always seen it as a first generation approach that over time ought to be replaced by more refined approaches,” he says.

Vedanta’s first candidate is VE-202, for inflammatory bowel disease, and should begin its first trial in the first half of next year, according Olle.

Johnson & Johnson, which inked a $339 million licensing deal with Vedanta in 2015, will be in charge of VE-202 development. Vedanta is broadening its efforts into infectious diseases (hospital-acquired infections that can’t be controlled by antibiotics), allergies, and potentially cancer. Everything in its pipeline is made from cocktails of live bacteria.

Olle says Vedanta can expand thanks to a deeper understanding how the immune system and gut microbes interact. Initially the company focused on microbes that might help tamp down immune responses—and thus treat autoimmune diseases like IBD.

But Vedanta has since identified microbes that do the opposite: they help rev up the body’s defenses, perhaps to mount a stronger fight against an infection or respond to cancer. Vedanta is trying to amass a library of these strains, much like a pharma company might have a slew of chemical compounds to screen through. “We’re trying to make this a more rational, controllable type of approach,” Olle says.

The new $50 million infusioncomes from new backers Rock Springs Capital, the microbiome-focused fund Health For Life Capital, and Invesco Asset Management (one of PureTech’s investors). PureTech also participated.

Vedanta recently moved out of Cambridge’s LabCentral incubator and into 9,000 square feet in Cambridge. It’s hired several executives, among them chief scientific officer Bruce Roberts, formerly of Genzyme, and head of manufacturing Dan Couto, recently of Sepracor.

The cash will help Vedanta drive “multiple” programs towards clinical testing, Olle says, boost its manufacturing capability, and double its staff to 30.

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