An unhealthy balance of gut microbes is associated with an elevated risk of death among people who have received a donor organ, study findings suggest.
The findings contribute to understanding the relationship between the gut microbiome and long-term health.
Specifically, the study showed a heightened risk of death from cancer and infection that was linked with a shift away from healthy gut microbial patterns, known as gut dysbiosis.
This affected patients regardless of whether the transplanted organ was a kidney, liver, heart or lung, the researchers report in the journal Gut.
Corresponding author Johannes Björk, PhD, from University Center Groningen in The Netherlands, noted that his group had previously shown that transplant patients experience a loss of bacteria that produce butyrate.
These short-chain fatty acids have a broad range of functions in the gut, including acting as anti-inflammatory and anti-obesity agents, as well as helping maintain gut wall integrity.
“The gut dysbiosis experienced by the organ recipients is partly driven by the use of strong immunosuppressive drugs which prevent organ rejection, coupled with a frequent use of antibiotics,” Björk pointed out.
“So while absolutely life-saving, immunosuppressants are clearly a double-edge sword.”
The team studied metagenomes from 1337 fecal samples in 766 kidney, 334 liver, 170 lung, and 67 heart transplant recipients.
These were then compared with samples from of 8208 people living in the same area of the northern Netherlands.
The average age of the transplant recipients was 57, and just over half were men. On average, they had received their transplant 7.5 years previously.
During a follow-up period of up to 6.5 years, 162 recipients died. This included 88 for whom the transplanted organ was a kidney, 33 in whom it was a liver, 35 with lung transplants, and six with a heart transplant.
In all, 28% died as a result of an infection, 23% from cardiovascular disease, 23% from cancer, and a quarter from other causes.
The researchers identified 23 bacterial species that were associated with all-cause mortality, both increased and decreased risk.
An abundance of four Clostridium species was associated with death from all causes, and specifically infection, with the same true for an abundance of Hangatella Hathewayi and Veillonella parvula.
High levels of Ruminococcus gnavus, but low levels of the butyrate-producing species Germigger formicilis, Firmicutes bacterium CAG 83, Eubacterium hallii and Faecalibacterium prausnitzi were associated with death from all causes, and cancer specifically.
Applying a machine learning algorithm revealed a second pattern of 19 bacterial species that were associated with all-cause mortality.
“Our results support emerging evidence showing that gut dysbiosis is predictive of long-term survival, indicating that gut-microbiome targeting therapies might improve patient outcomes,” the researchers concluded.
