‘Unhealthy’ gut microbiota linked to increased risk of death after organ transplant

“Unhealthy” gut microbiota patterns are linked to increased risk of death after solid organ transplantation, according to a study published online in the journal Intestine.

Although these particular microbial patterns are associated with death from any cause, they are specifically associated with death from cancer and infection, regardless of the organ (kidney, liver, heart or lung) transplanted, the results show.

The composition of the gut microbiota is associated with various diseases, including inflammatory bowel disease and diabetes. But few studies have the data needed to analyze the association between the gut microbiota and long-term survival, the researchers explain.

And while a shift from a normal pattern of microbes to an “unhealthy” pattern, known as gut dysbiosis, has been associated with an increased risk of death in general, it’s unclear whether it might also be associated with overall survival in specific diseases, they add.

To find out, they studied the relationship between gut dysbiosis and all-cause and non-cause mortality in solid organ transplant recipients, in whom the prevalence of gut dysbiosis is much higher than in the general population. This makes them an ideal group to study associations between gut dysbiosis and long-term survival, the researchers say.

They analyzed the microbiome profiles of 1,337 fecal samples provided by 766 kidney, 334 liver, 170 lung and 67 heart transplant recipients and compared them to the gut microbiome profiles of 8,208 people living in the same geographic area in the northern Netherlands.

The mean age of transplant recipients was 57 years, and more than half were men (784; 59%). 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: 88 kidney recipients, 33 liver recipients, 35 lung recipients, and 6 heart recipients. Forty-eight (28%) died of infection, 38 (23%) of cardiovascular disease, 38 (23%) of cancer, and 40 (25%) of other causes.

The researchers looked at several indicators of gut dysbiosis in these samples: microbial diversity; the extent to which their gut microbiome differed from the average microbiome of the general population; the prevalence of antibiotic resistance genes; and virulence factors that help bacteria invade cells and evade immune defenses.

The analysis found that the more the gut microbiome profiles of transplant recipients diverged from those of the general population, the more likely they were to die sooner after surgery, regardless of the organ transplanted.

Similar associations emerged for the abundance of antibiotic resistance genes and virulence factors.

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

For example, an abundance of four Clostridium species was associated with all-cause and infection-specific death, while an abundance of Hangatella Hathewayi and Veillonella parvula was associated with all-cause and infection-specific death.

High numbers of Ruminococcus gnavus, but low numbers of Germigger formicilis, Firmicutes CAG 83 bacteria, Eubacterium hallii and Faecalibacterium prausnitzi were associated with death from all causes and specifically from cancer.

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

The researchers then analyzed all bacterial species simultaneously using AI. This analysis revealed a second pattern of 19 different species, also associated with an increased risk of death.

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

But, the researchers conclude, “our results support emerging evidence that gut dysbiosis is associated with long-term survival, indicating that therapies targeting the gut microbiome could improve patient outcomes, although causal links must first be identified.”