High oral microbial diversity linked to poor lung function, mortality risk in IPF

Key takeaways:

• High oral microbial diversity in IPF is linked to decreased lung function and an elevated mortality risk.
• Researchers found a low mortality risk in patients with more Streptococcus receiving usual care.

Among patients with idiopathic pulmonary fibrosis, higher microbial diversity in the mouth negatively impacted lung function, according to results published in American Journal of Respiratory and Critical Care Medicine.

More diversity also raised the risk for mortality among patients who received usual care and no long-term antibiotics, according to researchers.

“While everyone thinks of IPF as being restricted to the lung, clearly the entire body system is afflicted — either as a consequence of the disease process or contributing to it,” Imre Noth, MD, professor of medicine and division chief of pulmonary & critical care medicine at University of Virginia, told Healio. “[The article is] for future work that could be crucial to better understand the oral-lung-gut immune axis.”

Using data from a large-scale, pragmatic, multicenter study (CleanUP-IPF trial), Noth and colleagues assessed 511 patients with IPF to find out how oral microbiota is linked to disease severity and death in this patient population.

Researchers collected DNA from a patient’s cheek using 16S rRNA gene analysis and shotgun metagenomic sequencing data of buccal swabs.

Notably, this study included a cohort receiving usual care and a cohort receiving long-term antibiotics.

Researchers used principal component analysis and linear regression models to find the relationship between microbiome data and disease severity, whereas when figuring out how the oral microbiome is linked to mortality, they used three different resources: Cox additive models, Kaplan Meier analysis and Cox proportional hazards models.

Among the various bacterial genera found in the mouth, Streptococcus appeared the most as demonstrated by a mean relative abundance of 49.43% across clinical samples.

At baseline, 490 patients had lung function data. Researchers observed a relationship between higher oral microbial diversity and reduced FVC in a multivariate regression model, with each 1-unit increment in the Shannon diversity index negatively impacting percent-predicted FVC (mean difference, –3.6; 95% CI, –5.92 to –1.29 percent predicted).

The link between microbial diversity and FEV₁ followed the same pattern as above, whereas the link between diversity and percent-predicted diffusing capacity of the lungs for carbon monoxide (n = 483) was not significant.

Looking specifically at Streptococcus in this model, researchers found that each 10% increase in the proportion of this genus helped preserve FVC (mean difference, 0.8; 95% CI, 0.16-1.43 percent predicted).

In terms of death, the risk for this outcome was heightened among patients with higher microbial diversity in the usual care cohort, with each 1-unit increment in Shannon diversity index raising the risk (HR = 1.73; 95% CI, 1.03-2.9).

“The fact that a decrease in oral microbial diversity was favorable was a surprise until we did more reading on some body locations being protected by certain pathogens,” Noth told Healio.

The presence of Streptococcus continued to be beneficial in patients with IPF when assessing survival. Having more of this bacterial genus (above 70% relative abundance) correlated to a lower mortality risk (HR = 0.85; 95% CI, 0.73-0.99).

Researchers noted that Streptococcus mitis was the primary species in the genus.

In contrast to patients receiving usual care, the link between oral microbial diversity and mortality risk was not significant among patients receiving antibiotics (either cotrimoxazole or doxycycline).

Researchers further found that the relationship between Streptococcus abundance and mortality risk was not significant in both antibiotic treatment groups.

“[In future studies] we may find that we need to know what the health of the mouth is to better decide treatments for IPF,” Noth told Healio. “We are working on linking the blood immune data to the microbiome.”

Reference:

• Bacteria in the mouth linked to pulmonary fibrosis survival. https://www.michiganmedicine.org/health-lab/bacteria-mouth-linked-pulmonary-fibrosis-survival. Published Feb. 5, 2024. Accessed Feb. 8, 2024.