Presence of Dolosigranulum pigrum in the nasopharynx and its relationship with respiratory health status in paediatric population

This study demonstrates that the nasopharyngeal presence of *Dolosigranulum pigrum* is significantly more prevalent in healthy children compared to those with invasive pneumococcal disease and is also associated with male sex, suggesting a potential protective role in pediatric respiratory health.

The Gist

Imagine your child's nose and throat (the nasopharynx) as a bustling, tiny city. This city is home to millions of microscopic residents—bacteria, viruses, and other microbes. Some of these residents are troublemakers who can cause sickness, while others are the "good guys" who keep the peace and protect the city from invaders.

This study is all about one specific "good guy" resident named Dolosigranulum pigrum (let's call him Dolo for short).

Here is the story of what the researchers found, explained simply:

1. The Mission: Who is Dolo?

Scientists have long suspected that Dolo is a superhero for children's respiratory health. He lives in the nose and throat and seems to act like a bodyguard. When Dolo is present, the city is usually healthy. When he is missing, the "bad guys" (like the bacteria that cause pneumonia or invasive pneumococcal disease) often take over.

The researchers wanted to know: What makes Dolo show up? And does he actually keep kids healthy?

2. The Investigation: Checking the City Logs

The team looked at the "city logs" (nasopharyngeal samples) of 140 children under 18. They divided the kids into three groups:

• The Healthy Citizens: Kids with no symptoms.
• The Sick-but-Mild: Kids with common viral colds (like a runny nose).
• The Emergency Cases: Kids with a serious, invasive bacterial infection called IPD (Invasive Pneumococcal Disease), which can be life-threatening.

3. The Big Discoveries

🏆 Dolo Loves Healthy Kids
The results were clear: Dolo was much more common in the healthy kids than in the sick ones.

• Healthy Kids: About 66% had Dolo living in their noses.
• Serious Infection Kids: Only about 33% had Dolo.
• The Metaphor: Think of Dolo as a security guard. In the healthy neighborhoods, the guard is on duty. In the neighborhoods where the "bad guys" (invasive bacteria) have broken in, the guard is missing.

👦 Boys vs. Girls: A Gender Surprise
The study found something interesting about gender. Boys were more likely to have Dolo than girls.

• The Metaphor: It's like a club where the bouncer (Dolo) seems to prefer letting boys in. Since boys are statistically more prone to severe respiratory infections, the researchers wonder if Dolo is working extra hard to protect them, acting as a natural shield that girls might not need as much.

🍼 The Breastfeeding Connection
The researchers checked if how a child was fed (breastfed or not) or how they were born (vaginal or C-section) mattered.

• The Result: While breastfed kids did seem to have Dolo a bit more often, the difference wasn't statistically huge in this specific study. However, the trend suggests that a "natural start" (breastfeeding) might help build a better community for Dolo to live in.

🦠 The Virus Factor
When kids had a virus (like a cold), Dolo was still there, but his numbers were lower.

• The Metaphor: Imagine a virus as a loud construction crew moving into the city. Even if the security guard (Dolo) is still there, the noise and chaos of the construction might make it harder for him to do his job effectively, or the virus might be pushing him out slightly.

4. Why Does This Matter?

This study is like finding a new key to a lock. We know that Dolo is a sign of a healthy respiratory system.

• The "Good Guy" Theory: Dolo doesn't just sit there; he actively fights the bad bacteria. He might produce acids or signals that stop dangerous bacteria from growing or invading the blood.
• The Future: If we can figure out exactly how to boost Dolo's population in a child's nose, we might be able to prevent serious infections like pneumonia or meningitis without using heavy antibiotics. It's like training the city's own security force to do the job.

The Bottom Line

This paper tells us that Dolosigranulum pigrum is a friendly neighborhood watchman. He is most likely to be found in healthy children and boys. When he is missing, the risk of serious bacterial infections goes up. Understanding how to keep Dolo happy and present in our children's noses could be a game-changer for keeping them healthy.

Technical Summary

1. Problem Statement

Respiratory tract infections (RTIs), particularly invasive pneumococcal disease (IPD), remain a leading cause of pediatric mortality. While pathogens like Streptococcus pneumoniae are well-known causes of disease, the role of the nasopharyngeal microbiome in modulating the transition from asymptomatic colonization to invasive disease is increasingly recognized. Specifically, Dolosigranulum pigrum, a commensal lactic acid bacterium, has been hypothesized to possess protective properties against respiratory pathogens. However, the specific epidemiological, clinical, and microbiological variables associated with the presence and abundance of D. pigrum in children with varying respiratory health statuses (healthy, viral infection, and invasive disease) require further elucidation.

2. Methodology

• Study Design: An ancillary case-control study utilizing data from a previously conducted cohort at Hospital Sant Joan de Déu Barcelona (2014–2018).
• Population: 140 children (<18 years) stratified into three groups:
  1. Healthy/Asymptomatic: n=65.
  2. Banal Viral Infection: n=48 (microbiologically confirmed).
  3. Invasive Pneumococcal Disease (IPD): n=27 (inpatients).
• Inclusion Criteria: Signed informed consent, no prior antibiotic exposure (or ≤24h for IPD), and exclusion of high-risk clinical groups.
• Sample Collection: Nasopharyngeal aspirates (NPAs) were collected and stored at -80°C.
• Microbiological Analysis:
  • Pathogen Detection: S. pneumoniae detected via lytA gene real-time PCR; serotyping performed.
  • Viral Detection: Multiplex real-time PCR (Allplex II RV16) for 15 respiratory viruses.
  • Microbiome Profiling: 16S rRNA gene sequencing (V3-V4 region).
  • Definition of D. pigrum Presence: Defined as relative abundance >0.1% of total sequences.
• Statistical Analysis:
  • Univariate analyses (Chi-square/Fisher's exact test, t-test/Mann-Whitney).
  • Multivariate Generalized Linear Models (GLM) with binomial distribution and logistic link to calculate Adjusted Odds Ratios (aOR).
  • Relative abundance comparisons using Kruskal-Wallis and pairwise Wilcoxon tests (log10-transformed data).

3. Key Contributions

• Sex-Based Disparity: The study identifies a significant sex-based difference in D. pigrum colonization, with males being more likely to carry the bacterium than females.
• Protective Association with IPD: It provides robust statistical evidence linking the presence of D. pigrum to a reduced risk of Invasive Pneumococcal Disease, independent of other variables.
• Abundance Gradient: The study moves beyond simple presence/absence to demonstrate a "dose-dependent" relationship, where the relative abundance of D. pigrum is highest in healthy children, intermediate in viral cases, and lowest in IPD cases.
• Viral Interaction: It clarifies the complex relationship between respiratory viruses and D. pigrum, showing that while univariate analysis suggests an inverse relationship, this is attenuated in multivariate models, though viral presence does correlate with lower D. pigrum abundance.

4. Key Results

• Prevalence: D. pigrum was detected in 56.4% (79/140) of the total cohort.
  • Healthy group: 67.7% (44/65).
  • Viral group: 54.2% (26/48).
  • IPD group: 33.3% (9/27).
• Multivariate Associations:
  • Health Status: Healthy children were significantly more likely to carry D. pigrum compared to IPD cases (aOR = 3.76; 95% CI: 1.12–12.59; p=0.028). No significant difference was found between healthy and viral groups or viral and IPD groups in the multivariate model.
  • Sex: Males were significantly more likely to be carriers than females (aOR = 2.21; 95% CI: 1.07–4.57; p=0.033).
  • Breastfeeding: A trend toward significance was observed (aOR = 2.33; p=0.063), suggesting breastfed children may be more likely to carry D. pigrum.
  • Viruses: Univariate analysis showed an association between absence of viruses and D. pigrum presence (p=0.02), but this lost significance in multivariate analysis (p=0.059).
• Relative Abundance:
  • Healthy children had significantly higher D. pigrum abundance than IPD cases (p=0.001).
  • Within the healthy group, virus-negative children had the highest abundance, significantly higher than both viral cases and IPD cases.
• Pneumococcal Carriage: While S. pneumoniae carriage was lower in D. pigrum carriers (62.8%) compared to non-carriers (70.5%), this difference was not statistically significant.

5. Significance and Implications

• Mechanism of Protection: The findings support the hypothesis that D. pigrum plays a protective role against severe respiratory disease, potentially by inhibiting the transition of S. pneumoniae from colonization to invasion, rather than just preventing colonization itself.
• Ecological Adaptation: The higher prevalence in males suggests a potential evolutionary or ecological adaptation, possibly compensating for the known higher susceptibility of males to lower respiratory tract infections.
• Therapeutic Potential: The dose-dependent nature of the protection suggests that D. pigrum could be a candidate for probiotic interventions or microbiome-based therapies to prevent IPD and severe RTIs.
• Limitations: The study acknowledges a small sample size for the IPD group (due to strict antibiotic exclusion criteria) and the limitations of 16S rRNA amplicon sequencing for species-level resolution. Future studies should utilize full-length sequencing or qPCR to validate these findings.

In conclusion, this study reinforces Dolosigranulum pigrum as a key beneficial commensal in the pediatric nasopharynx, strongly associated with respiratory health and male sex, and suggests its abundance is a critical factor in preventing invasive pneumococcal disease.