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Monday, 25 July 2016

What are gut bacteria doing in critically ill lungs?

From recent research, detecting bacteria that normally should be in the gut inside lungs of patient and animals could change response of care giver in Intensive Care Unit (ICU). It has been reported that in critically ill patient gut bacteria are been isolated from their lungs a location where they normally shouldn’t survive and this had led to more severe condition of the patient as the normal flora are been outnumbered.  The scientist that found out about this published it in Nature Microbiology, and consisted of teams of scientist from the University of Michigan Medical School. They concluded in their research that beyond initial perception it is very much possible that change in microbiota of the lung can affect the severity of illness linked with lung dysfunction.
This conclusion was reached when the researcher found out the effect in 68 patients with Acute Respiratory Distress Syndrome (ARDS) and in rodents as test organism. With the aide bacterial culture techniques and genetic tools, they were able to study the lung microbiome of humans with ARDS for the first time and compare them to samples from healthy volunteers. It’s been on record that over 200,000 Americans develop ARDS each year and many of them are among the million Americans who develop sepsis. Nearly half of ARDS and sepsis patients die from those conditions."Our results suggest that in our past attempts to find treatments for sepsis and ARDS, we may have been overlooking a major part of the story," says lead author Robert P. Dickson, M.D., a critical care physician and laboratory scientist. "Virtually all of our attempts to treat these critical illnesses have been aimed at fixing the disordered inflammation and tissue injury we can see in our patients. But our study raises the possibility that this inflammation and injury may actually be downstream consequences of an upstream source: disordered bacterial communities in the gut and lung."

A vicious cycle
The researcher in their opinion believes that patients with these respiratory conditions may actually be stuck in a vicious cycle caused by dysbiosis - an out-of-whack microbiome. According to their discoveries, they suggest that the cascade involve is like looking into age long question of "chicken and the egg" feedback loop. Changes in the microbiome lead to inflammation, as the body's immune system tries to fend off what it sees as invaders. And the inflammation in turn injures the delicate lung tissue. The injury and inflammation result in changes to the environment within the lung, thus, allowing microbes that don't normally grow there to invade and/or multiply if initially they are present but with lower loads. Hence, in order to improve patient’s condition, ways to break the vicious cycle have to be sought so as to keep the normal floral relatively normal.  

Most importantly, the quest to know the route in which the gut bacteria entered the lung was undertaken by the researchers. However, in the animals with sepsis, they did rule out the usual route by which microbes get into the lung every day - through the upper respiratory tract of the mouth, nose and throat. One possible explanation - one that researchers have speculated about since the 1950's - is that in patients with critical illness, the walls of the intestines get "leaky," and bacteria escape and travel upward into the lungs. Another potential explanation is that small numbers of these gut bacteria were present in the lungs all along, but couldn't grow for lack of the proper environmental conditions. "We've only recently started thinking of the lungs as an ecosystem," says Dickson. "So we're just now sorting out the rules for how these bacterial communities get established, both in health and in critical illness."

Continuing the Investigation
The lead researcher - Dickson noted that the new findings explain what critical care teams have known for quite some time now that the gut microbiome is in a way linked to a person's chances of surviving a critical illness. Since, 1950’s animal studies have shown that pre-treatment of the gut with antibiotics before trauma or other critical illness can protect against lung injury and death.  A common procedure in some countries is to pre-treat patient with antibiotics in order to selectively decontaminate the digestive tract and more often uninfected patients in ICU are treated with antibiotics to suppress microbiome so as to prevent organ failure. But in the US because of concerns that antibiotic use could accelerate the rise of resistant strain to modern antibiotics such pre-treatment is not carried out.

Presently, in a bid to unravel lung-gut microbiome mystery, Dickson and colleagues have already begun capturing samples from more patients at risk for ARDS in the intensive care units of U-M's University Hospital. U-M is part of the National Institutes of Health's ARDS clinical trials network called Prevention and Early Treatment of Acute Lung Injury, or PETAL. Dickson is also an associate director of U-M's Center for Integrative Research in Critical Care, which brings scientists, engineers and clinicians together to advance understanding of diseases like ARDS.

To show that the gut bacteria were alive in the lungs, not just detectable as DNA fragment from dead bacteria tools such as oxygen-free growth chambers, germ-free animal facilities and advanced genetic sequencing and cultivation tools will be used. This will be made possible through University of Michigan Medical School’s Host Microbiome Initiative, one the research have access to through the lead researcher who is an associate director at U-M’s Center.
"In the long run, we need to start thinking of the microbiome as an organ that can fail in critically ill patients," says Dickson. "We're studying how it gets disordered, how it impacts other organs, and how we can fix it. The importance of the microbiome in the ICU has been clear for decades, but with these new tools we're finally able to ask and answer the right questions. It's a really exciting time."

With the increase in research on how Gut bacteria affect us and more of Host-Pathogen relationship, this is a research worth following up.

Article: “Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome” Robert P. Dickson, Benjamin H. Singer, Michael W. Newstead, Nicole R. Falkowski, John R. Erb-Downward, Theodore J. Standiford & Gary B. Huffnagle, Nature Microbiology, doi:10.1038/nmicrobiol.2016.113, published online 18 July 2016.

Adapted from Medical News -

The new findings suggest that a cycle of microbiome disruption, inflammation and tissue injury may be involved in critical illness involving the lungs
Image Credit: University of Michigan



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