When sepsis patients face brain impairment, is gut bacteria to blame?

March 7, 2018, University of Michigan
Credit: University of Michigan

Surviving a critical illness is no small feat, but it's only half the battle for many patients. Serious complications can still result after an illness appears to have cleared.

One of those resulting dangers is .

"Many will experience cognitive impairments or emotional difficulties that are equivalent to mild and can persist for months or years after their hospitalization," says Benjamin Singer, M.D., Ph.D., an assistant professor of internal medicine at Michigan Medicine.

The source of that impairment isn't always clear, however.

Singer is the lead author of a study, published in the American Journal of Respiratory and Critical Care Medicine, that sought to examine a potentially serious connection: whether gut bacteria cause dysfunction in patients.

"We already know from previous studies that sepsis results in long-term brain dysfunction and that neuroinflammation plays a role in brain injury during the infection," says Singer, who specializes in pulmonary disease and .

"But we hypothesized that the is directly related to gut bacteria independently moving to the brain and perhaps triggering an immune response that leads to longer-term effects from the injury."

Common thread in mice and humans

Although previous studies have suggested that , or microbiome, may increase the likelihood of lung inflammation during sepsis, Singer and his research colleagues note that the microbiome's effect on other organs, such as the brain, has been unstudied.

Singer and the team used mice models and brain tissue of deceased patients (the latter source came from the University of Michigan Brain Bank) to carry out the study. Mice that survived sepsis were compared with mice controls; brain tissue of patients who died of sepsis was compared with tissue of patients who died of noninfectious causes.

In addition, the researchers used 16S rRNA gene sequencing, a technique that identifies bacteria present in a sample via their DNA signature, in the mice models and human tissues to identify which gut bacteria fueled their hypothesis.

"The traditional thing to do in a microbiology lab is take a sample and try to grow bacteria from it in the lab under particular conditions and see what you get," Singer says. "We know, though, that there are many bacteria that are important in the gut microbiome but that don't grow in the traditional methods.

"We can take a sample and isolate the DNA from it and sequence the 16S rRNA gene. Then we can compare the sequences of those genes to a database of known bacteria and identify many more bacteria in the tissue, instead of relying on what grows in a culture."

Results supported the hunch: Researchers found that gut bacteria present in the brains of the mice five days after surviving sepsis—but gone by 14 days after the infection—were associated with levels of S100A8, a marker of neuroinflammation.

Singer notes that while the human tissue analysis was a small cohort, the research team noticed distinct differences between patients who died of sepsis and those who died of noninfectious causes.

"Anytime someone dies, bacteria grow out of control because the immune system is not keeping the bacteria in the body in check," Singer says. "But we found that the bacteria we isolated from patients that died of sepsis were quite different from the run-of-the-mill bacteria that sit in the body after a person dies—and did appear to be associated with neuroinflammation in the brain."

As was observed in mice, the gut bacteria detected in brains of patients who died of sepsis correlated with the S100A8 inflammation marker.

Implications for real-life care

The study's conclusion: Sepsis causes gut bacteria to locate in the brain for several days and ultimately resolves in the weeks after the onset of illness.

Because the gut bacteria were present in the brains of both the mice and humans who died of sepsis—and those bacteria were associated with the marker for inflammation of the brain—the findings indicate gut bacteria do appear to play a role in brain dysfunction after sepsis.

"The larger question raised by this study is: Is there anything we can do to intervene and change the consequences of critical illness for survivors?" Singer says. "Results from the microbiome and lung inflammation study and this one suggest that one, there are bacteria that are directly involved in organ injury, and two, the bacteria that have disseminated to different organs during sepsis are not always the bacteria that the clinical laboratory identifies in the blood culture and that are the target of your antibiotic treatment."

The results could have implications for providing care.

Singer notes the study also suggests, although additional research would be needed, that treating could help avoid or reduce brain dysfunction.

"Giving oral antibiotics to remove those in the gut may potentially reduce long-term effects of ," Singer says.

Explore further: Gut microbes protect against sepsis—mouse study

More information: Benjamin H Singer et al, Bacterial Dissemination to the Brain in Sepsis, American Journal of Respiratory and Critical Care Medicine (2017). DOI: 10.1164/rccm.201708-1559OC

Related Stories

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Traumatic brain injury causes intestinal damage, study finds

December 6, 2017
University of Maryland School of Medicine (UMSOM) researchers have found a two-way link between traumatic brain injury (TBI) and intestinal changes. These interactions may contribute to increased infections in these patients, ...

Scientists find potential mechanism for deadly, sepsis-induced secondary infection

September 14, 2017
In mice, an infection-induced condition known as sepsis may increase the risk of life-threatening secondary infection by preventing recruitment of infection-fighting cells to the skin, according to new research published ...

Scientists illuminate role of staph toxins in bacterial sepsis

February 2, 2017
Staphylococcus epidermidis bacteria are a significant health concern for hospitalized infants, children and anyone with implanted medical devices. The bacteria—typically skin dwellers—can infect the bloodstream and cause ...

Major changes in balance of gut bacteria occur soon after serious injury/trauma

October 23, 2017
Major changes in the balance and make-up of gut bacteria occur within 72 hours of serious injury/trauma, reveals a small study, published in the online journal Trauma Surgery & Acute Care Open.

Bacteria found in Alzheimer's brains

July 17, 2017
Researchers in the UK have used DNA sequencing to examine bacteria in post-mortem brains from patients with Alzheimer's disease. Their findings suggest increased bacterial populations and different proportions of specific ...

Recommended for you

Scientists grow human esophagus in lab

September 20, 2018
Scientists working to bioengineer the entire human gastrointestinal system in a laboratory now report using pluripotent stem cells to grow human esophageal organoids.

Study identifies stem cell that gives rise to new bone and cartilage in humans

September 20, 2018
A decade-long effort led by Stanford University School of Medicine scientists has been rewarded with the identification of the human skeletal stem cell.

Researchers identify human skeletal stem cells

September 20, 2018
Human skeletal stem cells that become bone, cartilage, or stroma cells have been isolated from fetal and adult bones. This is the first time that skeletal stem cells, which had been observed in rodent models, have been identified ...

A new app enables a smartphone to ID bacteria in just one hour

September 20, 2018
In a potential game changer for the health care industry, a new cell phone app and lab kit now allow a smartphone to identify bacteria from patients anywhere in the world. With the new app, doctors will be able to diagnose ...

Synthetic sandalwood found to prolong human hair growth

September 19, 2018
A team of researchers led by Ralf Paus of the University of Manchester has found that applying sandalwood to the scalp can prolong human hair growth. In their paper published in the journal Nature Communications, the group ...

Zombie cells found in brains of mice prior to cognitive loss

September 19, 2018
Zombie cells are the ones that can't die but are equally unable to perform the functions of a normal cell. These zombie, or senescent, cells are implicated in a number of age-related diseases. And with a new letter in Nature, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.