Scientists discover link between gut microbe and long-term mortality

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A study by researchers at the University of Turku in Finland has demonstrated a strong association between Enterobacteriaceae and deaths from respiratory and liver disease, among other illnesses.

The research represents the largest long-term population study in the world to examine the potential link between human gut microbiota and future health and mortality, says the authors.

Associate Professor Leo Lahti explained, “Finnish population studies are unique in their extent and scope even on a global scale. With new data science methods, we are now able to study more closely the specific connections between microbiota and, for example, ageing and incidence of common diseases.”

Microbiome and health

Human microbiota is highly individual and consists of vast amounts of different bacteria and other micro-organisms. Several cross-sectional studies have previously established a link between gut microbiota and lifestyle but there is limited comprehensive follow-up data to characterise the associations between microbiome composition and health. 

Observations from this study suggest that certain enterobacteria combinations can make individuals more or less prone to increased mortality.

Specific taxonomic configurations of the human gut microbiome may reflect health-associated changes that are linked to increased mortality, or potentially play a unique role in the maintenance of health and development of incident disease,” the report says.

Study methodology

Study data was sourced from the FINRISK 2002 health risk-factor survey conducted by the Finnish Institute for Health and Welfare. It involved a random cohort of 7,055 Finnish adults with an average age of 49.5 years, of which 55.1% were female.

Subject’s faecal microbiome composition was analysed in 2002 with stool sample collections and cross-sectional phenotyping to identify taxonomic composition. Follow-up data was obtained from electronic health registers and death certificates in 2017 to analyse the long-term health status and mortality of participants.  

Links between mortality and key features of microbiome composition were investigated, including local (alpha) and regional (beta) diversity, genus abundances, taxonomic co-occurrence networks and functional predictions.

Factors known to affect microbiome composition and mortality risk were also considered such age, sex, BMI, smoking, diabetes, systolic blood pressure and antihypertensive medication.

Researchers focused on the 91 genus-level taxonomic groups detected in >1% of the study participants. This included bacterial genera (87) as well as viruses (1) and archaea (3), with a median relative abundance of 99.3%.

We developed a machine learning algorithm that screened the data for microbial species having a significant association with mortality among the research subjects in the following two decades after the sample was taken,” explained Lahti. 

Mortality predictions

Analyses revealed that participants with a greater abundance of Enterobacteriaceae and the prostrate cancer cell line (PC3) were at greater risk of death (49% and 34% respectively) from gastrointestinal and respiratory illnesses compared to participants registering lower amounts.

According to the report, the prevalence of PC3 was precipitated by species of the Enterobacteriaceae family that form part of the normal gut microbiome and can cause infectious diseases in the gut and other body sites.

The researchers noted: “Our analysis provides a systematic quantification of the long-term health associations of the human faecal microbiome. These associations can be observed both in the Eastern and Western Finns who have differing genetic backgrounds, lifestyles and mortality rates.”

An abundance of other individual enterobacteria strains were also linked to mortality and total Enterobacteriaceae was associated with liver disease.

Teemu Niiranen, Professor of Medicine at the University asserts that studying the composition of gut microbiota could improve mortality predictions, “even while taking into account other relevant factors, such as smoking and obesity”.

He adds: “The data used in this research make it possible for the first time to study the long-term health impact of the human gut microbiota on a population level.”

Source: Nature Communications

‘Taxonomic signatures of cause-specific mortality risk in human gut microbiome’

DOI: doi.org/10.1038/s41467-021-22962-y

Authors: Aaro Salosensaari et al.