Misplaced Gut Bacteria Could Change Critical Care Maxims

A new study suggests that gut microbiome disruption may play a key role in sepsis and acute respiratory distress syndrome (ARDS) by infecting the lungs and other tissues.

Researchers at the University of Michigan (Ann Arbor, USA) used genetic tools and bacterial culture techniques to study the lung microbiome in 68 patients with ARDS, and compared them to samples from healthy volunteers. They also examined specimens from a murine model of induced sepsis. They found evidence that the lung microbiome was enriched with gut bacteria, both in the murine model of sepsis and in the humans with established ARDS.

An ecological analysis identified the lower gastrointestinal (GI) tract, rather than the upper respiratory tract, as the likely source community of post-sepsis lung bacteria. In bronchoalveolar lavage fluid from the humans with ARDS, gut-specific bacteria were common and abundant, undetected by culture, and correlated with the intensity of systemic inflammation. Analysis revealed that alveolar tumor necrosis factor (TNF-α), a key mediator of alveolar inflammation in ARDS, was significantly correlated with the altered lung microbiota.

The researchers believe that patients with sepsis and ARDS may actually be trapped in a vicious cycle caused by microbiome dysbiosis; changes in the microbiome lead to inflammation; that inflammation in turn injures delicate lung tissues. The injury and inflammation subsequently allow translocation of bacteria from the gut to the lungs, or alternatively change the microenvironment within the lung to allow microbes present in low levels to multiply. The study was published on July 18, 2016, in Nature Microbiology.

“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,” said lead author critical care physician Robert Dickson, MD. “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.”

ARDS is a disease of the alveoli of the lungs that leads to decreased exchange of oxygen and carbon dioxide (CO2). It is associated with several pathologic changes: the release of inflammatory chemicals, breakdown of the cells lining the lung's blood vessels, surfactant loss leading to increased surface tension in the lung, fluid accumulation in the lung, and excessive fibrous connective tissue formation. The condition affects an estimated 2.2 million people worldwide each year, and has a high mortality rate of 20-50%.

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