“Unhealthy” gut microbiome patterns are associated with increased risk of death after organ transplantation

“Unhealthy” gut microbiome patterns are associated with an increased risk of death after organ transplantation, according to a study published in The Journal of Diseases. Colon.

While these particular microbial patterns are associated with deaths from all causes, evidence suggests they are particularly associated with deaths from cancer and infections, regardless of which organ – kidney, liver, heart or lung – was transplanted.

The composition of the gut microbiome has been linked to several diseases, including inflammatory bowel disease and diabetes, but few studies have data to analyze the relationship between the gut microbiome and long-term survival, the researchers explain.

And while a shift from the normal microbial pattern to an “unhealthy” pattern, called gut dysbiosis, has been generally associated with an increased risk of death, it is not clear whether this might also be associated with overall survival rates in certain diseases, they add.

To find out, they examined the relationship between gut dysbiosis and death from all and specific causes in solid organ transplant recipients, where the prevalence of gut dysbiosis is much higher than in the general population. This makes them an ideal group to study the links between gut dysbiosis and long-term survival, the researchers say.

They analyzed the microbiome profiles of 1,337 stool samples from 766 kidney, 334 liver, 170 lung and 67 heart transplant recipients and compared these with the gut microbiome profiles of 8,208 people living in the same geographical region in the north of the Netherlands.

The average age of transplant recipients was 57 years, and over half of them were men (784; 59%). On average, they had received their transplant 7.5 years previously.

During an observation period of up to 6.5 years, 162 recipients died: 88 kidney, 33 liver, 35 lung and six heart recipients. 48 (28%) died from infection, 38 (23%) from cardiovascular disease, 38 (23%) from cancer and 40 (25%) from other causes.

The researchers examined several indicators of gut dysbiosis in these samples: microbial diversity, how different their gut microbiome was from the average microbiome of the general population, the prevalence of antibiotic resistance genes and virulence factors that help bacteria enter cells and evade immune defenses.

The analysis showed that the more the gut microbiome patterns of the transplant recipients differed from those of the general population, the more likely they were to die sooner after the procedure – regardless of the transplanted organ.

Similar correlations were also observed in the frequency of antibiotic resistance genes and virulence factors.

The researchers identified 23 bacterial species in all transplant recipients that were associated with an increased or decreased risk of death from all causes.

For example, high prevalence of four Clostridium species was associated with deaths of all types, particularly infections, while high prevalence of Hangatella hathewayi and Veillonella parvula was associated with deaths of all types, particularly infections.

And high numbers of Ruminococcus gnavus but low numbers of Germigger formicilis, Firmicutes bacterium CAG 83, Eubacterium hallii and Faecalibacterium prausnitzi have been associated with deaths of all kinds, especially cancer.

These last four species all produce butyrate, a short-chain fatty acid that, among other things, has anti-inflammatory properties and helps maintain the integrity of the intestinal walls.

The researchers then used artificial intelligence to analyze all bacterial species simultaneously. This revealed a second pattern of 19 different species that were also associated with an increased risk of death.

This is an observational study and therefore no definitive conclusions can be drawn about the causal role of specific bacteria.

But the researchers conclude: “Our results support recent findings showing that gut dysbiosis is associated with long-term survival. This suggests that therapies targeting the gut microbiome could improve patient outcomes, although causal relationships should first be identified.”