In a recent study published in The Lancet Microbe, researchers investigated the association between gut microbiota composition and risk of infection-related hospitalization. Using 16S rRNA sequencing, they characterized the diversity and abundance of gut bacteria in two large, independent, European population-based cohorts.
Study findings revealed that gut microbiota compositions, specifically the abundance of butyrate-producing bacteria, may protect against severe hospitalization-requiring infections.
Study: Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies. Image Credit: Drazen Zigic/Shutterstock.com
Background
Despite substantial advances in modern medicine, infectious disease significantly burdens human healthcare. The Global Burden of Disease study (2019) estimated that almost 25% of all annual mortality could be attributable to severe infections.
These findings imply that current prevention and treatment modalities are insufficient in curtailing the impacts of infectious diseases and necessitate the discovery of novel strategies to prevent infections severe enough to merit hospitalization and/or death.
Recent research by the current authors and others has suggested that human gut microbial composition may be intrinsically linked to infection immunity.
A growing body of research reports that most patients with severe infections depict gut microbial perturbations at hospitalization initiation (before the onset of treatment, the latter of which exacerbates gut dysbiosis).
Mouse models have supported these observations, linking infections with reduced intestinal anaerobic bacterial abundance and a corresponding increase in potentially pathogenic gut microflora.
Unfortunately, human-derived data is mainly observational, with externally validated, geographically controlled outcomes severely lacking from the literature.
About the study
Previous research by the current authors reported an association between butyrate-producing gut-bacterial depletions and a heightened risk of respiratory infections in human patients.
The present study builds upon that research and hypothesizes that gut microbial composition and relative abundance may affect an individual's susceptibility to severe, hospitalization-requiring infections.
Study methodology and outcomes reporting complied with the Strengthening The Organizing and Reporting of Microbiome Studies (STORMS) reporting guidelines.
Data from the study was derived from two independent Europe-based large-scale population cohorts – the Netherlands-based HELIUS study and the Finland-based FINRISK 2002 study. Both cohorts were national hospitalization- and mortality-linked prospective studies.
HELIUS comprises Dutch citizens (ages 18-70) from Amsterdam, stratified by ethnicity. FINRISK includes random samples of adults from six Finnish regions (ages 25-74).
Data were collected using questionnaires, physical examinations, and fecal sample evaluations. All data was linked to participants' medical and demographic records, which were used to determine primary (hospital admission or mortality) outcomes.
Following the Earth Microbiome Project protocols, fecal samples were subjected to 16S rRNA sequencing (Illumina) to determine gut bacteria composition, α-diversity, and relative abundance (Shannon Diversity Index).
Differences in community composition between participants requiring hospitalization and those that did not were computed using permutational multivariate analysis of variance (ANOVA) with Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC) corrections applied.
Study findings
The combined participant strength of both cohorts was 10,699 (HELIUS – 4,248; FINRISK – 6,451).
The gut microbial composition across cohorts was comprised predominantly of Firmicutes (Bacillota) and Bacteroidetes, with mean relative abundances of 65.9% and 24.1%, respectively. 3.6% of the HELIUS cohort and 7.0% of the FINRISK study suffered severe infections over the study and subsequent follow-up (6 years). Infections of the lower respiratory tract were the most common.
Outcomes groups (severe infections versus healthy) displayed permutation testing-confirmed separations in gut bacterial community composition, with Veillonella and Streptococcus relative abundances substantially higher in the hospitalization or mortality group.
In contrast, healthy participants displayed a higher relative abundance of Butyrivibrio, an anaerobic butyrate-producing obligate microbe.
"…these data showed that, in two independent cohorts, baseline gut microbiota composition differed between participants hospitalised with an infection during follow-up and those without infection-related hospitalisation, similarly driven by an increase in Veillonella and decrease of the obligate anaerobe Butyrivibrio."
Cox proportional hazard ratio estimations revealed that the relative abundance of butyrate-producing bacteria directly contributed to reduced severe infection risk. Every 10% increase in the relative abundance of these bacteria was associated with a 0.75 Cause-Specific Hazard Ratio (csHR).
Neither corrections for potential confounders (sex, age, ethnicity, alcohol usage, smoking, or comorbidities) nor the compositional nature of the microbiome altered these findings.
Together, these results highlight the relative abundance of butyrate-producing bacteria, directly associated with a decreased risk of hospitalization-requiring or mortality-causing infections.
Participants with a body mass index (BMI) exceeding 30 km/m2 were the exception, with BMI being the only confounding variable that altered these findings. In brief, BMIs indicative of obesity essentially eliminated the observed association.
Conclusions
The present study highlights that in the two large independent European cohorts investigated, a higher abundance of anaerobic butyrate-producing gut bacteria was associated with substantial reductions in the risk of future severe infections.
These findings suggest gut microbiota as a potentially easily modifiable risk factor in preventing hospitalization-requiring infections.
If validated by interventional studies, these results may restrict future human susceptibility to systemic infections and inform clinicians and policymakers of the best dietary interventions to prevent the transmission of contagions at the population scale.
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