A 58-year-old man admitted to the ICU with severe sepsis from pneumonia.
Intubated on day 2. Broad-spectrum antibiotics started. Clinical improvement by day 5.
Cultures negative. Antibiotics de-escalated. Extubation planned.
Day 10: Fever spikes. New infiltrate on chest X-ray. Enterococcus faecium bacteremia.
This secondary infection just appeared "suddenly"— except it didn't, really.
The pathogen was always there. Colonizing and Multiplying in a disrupted microbiome.
What if we could see it happening, in real time? During colonization, when intervention might prevent infection entirely.
This is no longer hypothetical. The technology already exists today - Microbiome profiling.
What Does Microbiome Profiling Actually Show?
While Culture asks:
→ Is this pathogen present?
Microbiome profiling asks:
→ What does the entire village aka ecosystem look like?
→ Are protective bacteria present?
→ Is colonization resistance intact?
→ Is a pathogen dominating?
All that difference matters for prevention.
In our ICU patient:
Day 1-2 (ICU admission): Microbiome profiling would show rapid, profound disruption. Studies show up to 90% of gut commensals can be lost within the first 6 hours of critical illness. 😳
Day 3-7: Enterococcus expands from 5% to 60% of the gut microbiome. Protective species like Faecalibacterium and Bacteroides disappear. 😳
Mind you, Still no fever. Surveillance cultures negative. But colonization resistance has failed.
Day 10-14: Bacteremia occurs in a patient whose microbiome predicted it days earlier.
What if we saw this at day 5?
And triggered targeted intervention such as selective decontamination, probiotic strategies, microbiome restoration, modified prophylaxis, heightened surveillance etc for this specific patient.
This is preventive microbiome medicine.
Metagenomics makes this possible.
It is no longer just theoretical.
A 2023 study published in Nature Medicine followed critically ill patients prospectively and found that intestinal dysbiosis was directly linked to impaired immune defense and increased infections.
The gut microbiome and systemic immunity functioned as an integrated system (aka A MetaSystem)
When one failed, the other followed.
Patients who later developed hospital-acquired infections showed earlier and more profound depletion of protective species like Faecalibacterium prausnitzii, with progressive overgrowth of pro-inflammatory Enterobacteriaceae and Enterococcus.
These changes were visible before clinical infection occurred.
A separate multi-center study across four ICUs analyzed 115 critically ill patients and demonstrated that critical illness causes rapid, significant microbiome disruption aka dysbiosis by wiping out health-promoting microbes while favoring an overgrowth of disease causing microbes.
This pattern is clear and reproducible:
Enterococcal species dominating the gut microbiome in ICU patients appear to predict subsequent bacteremia and multiple organ failure.
Progressive depletion of health-promoting organisms like Faecalibacterium, with increased abundance of pro-inflammatory taxa of the Enterobacteriaceae family, precedes clinical infection by days to weeks.
Interestingly, the same pattern holds for ventilator-associated pneumonia.
Research shows that the lung microbiome in ARDS becomes enriched with intestinal microbes— from a disrupted gut—contributing to lung inflammation and damage.
Clinical microbiology of VAP in the ICU reveals a high prevalence of gut-derived pathogens: E. coli, Klebsiella, Enterobacter, and others.
These are not random infections.
But rather, they are the direct result of gut dysbiosis allowing pathogen translocation and aspiration of gut-derived organisms.
A prospective pilot study analyzing both lung and gut microbiomes in mechanically ventilated ICU patients found that microbial diversity declined more significantly in infected patients than in controls.
Distinct microbial patterns in both lung and gut microbiota were associated with infection and clinical outcomes, suggesting the gut and lung microbiomes may serve as predictive markers for clinical outcomes in critically ill patients.
These patterns are visible days to weeks before clinical infection, while traditional diagnostics show nothing until infection occurs.
Microbiome Stewardship Needs Microbiome Diagnostics
In Edition 4, we established that antimicrobial stewardship is microbiome stewardship— preserving colonization resistance to prevent infections.
But, we're practicing microbiome stewardship blind.
We know broad-spectrum antibiotics disrupt microbiomes. We narrow when we can. We shorten duration when possible.
But we can't see:
Which patients have severe vs. mild disruption
When colonization resistance has actually failed
Which patients are at highest risk for infection
When recovery is happening vs. when intervention is needed
📌Microbiome diagnostics aka mNGS is changing all of that.
Metagenomics makes colonization resistance visible.
It turn microbiome stewardship from educated guessing into precision medicine.
This enables the shift from reactive infection treatment to proactive prevention.
That's why this matters for ID.
Cost and access are real barriers. mNGS runs $$$ per sample. Not every institution offers it. Insurance coverage is inconsistent. The patients who need it most often can't access it.
The evidence is still building. We have compelling proof-of-concept studies showing microbiome signatures predict infection. We don't yet have large RCTs showing microbiome-guided intervention improves outcomes.
Interpretation is complex. Not every lab can analyze microbiome data correctly. Not every clinician knows what to do with results.
These limitations are very real.
But here's what's also real: Decisions about these technologies are being made NOW at institutions across the country.
And often, ID isn't leading those decisions.
Who's Making the Decisions
Right now:
Diagnostic companies are marketing mNGS to ICU directors and critical care teams
Critical care is building microbiome surveillance protocols independently
Hospital administrators are evaluating which platforms to purchase
Lab directors are deciding which tests to offer and who can order them
Often without ID involvement.
And then we get consulted after:
Protocols are poorly designed
Tests are misinterpreted
Inappropriate interventions cause complications
Infections occur that monitoring should have prevented
What ID Leadership Looks Like
If microbiome diagnostics are going to enable preventive medicine, ID should be leading:
Platform evaluation: Which technology is appropriate for infection risk prediction in ICU patients?
Utilization criteria: Which high-risk ICU populations warrant monitoring? When does cost justify use?
Interpretation frameworks: What microbiome findings predict VAP, bacteremia, C. diff? When do we intervene?
Integration with stewardship: How do we use microbiome data to guide antimicrobial decisions in critical care?
This is core ID expertise.
Infection risk assessment. Diagnostic stewardship. Intervention criteria.
But we must claim it, first.
Ask: Is your hospital evaluating microbiome diagnostics? Who's involved in that decision?
Learn: Understand what these technologies can show and when evidence supports use
Position yourself: Be ready to provide ID perspective when discussions happen
The technology exists. The evidence is building. Implementation is happening.
The question is whether ID physicians will lead it.
Or whether we'll consult on ICU-acquired infections that microbiome monitoring should have prevented—using protocols designed without our input.
What's Next
In the next edition: Building preventive microbiome medicine programs at your institution.
What would an ID-led microbiome medicine actually look like in practice? How do we make the case to leadership? What infrastructure do we need?
And how do we claim leadership before other specialties build this without us?
Your Turn
Have you seen cases where microbiome profiling could have predicted secondary infections?
Let's talk in the comments.
👋🏿 Hi! I'm Dr Tina Agbaosi
👩🏿⚕️ Infectious Diseases physician and Metagenomics enthusiast. Better tools → Better decisions → Better outcomes.