Sepsis is a life-threatening condition where the body’s response to infection causes severe damage. Scientists used advanced genetic tools to search through thousands of genes and proteins to find which ones might be good targets for new medicines. They identified 6 genes and 21 proteins that appear connected to sepsis risk, then tested their top candidates in mice with sepsis-like conditions. The genes they found control immune system functions and inflammation—two key problems in sepsis. This research could help doctors develop better treatments for this serious disease that kills many people worldwide.

The Quick Take

  • What they studied: Which genes and proteins might be good targets for new sepsis medicines by analyzing genetic data from thousands of people and testing findings in mice
  • Who participated: The study used genetic information from large databases (UK Biobank and FinnGen) containing data from hundreds of thousands of people, plus laboratory experiments in mice with sepsis-like illness
  • Key finding: Researchers identified 6 genes and 21 proteins linked to sepsis risk. Some appear protective (like HDC and IFI27), while others seem harmful (like CTSO and BTN3A2). Lab tests in mice confirmed these findings matched real biological changes
  • What it means for you: This research may eventually lead to new medicines for sepsis, but these findings are still in early stages. Current sepsis treatment hasn’t changed yet—this work helps scientists understand where to focus drug development efforts

The Research Details

Scientists used a technique called Mendelian randomization, which is like a genetic detective tool. Instead of doing traditional experiments, they analyzed genetic information from huge databases to find which genes might cause sepsis. They looked at two types of genetic data: eQTL data (which shows how genes affect protein production) and pQTL data (which shows how genetic changes affect protein levels in the blood). They then cross-checked these findings against actual gene expression patterns from sepsis patients’ tissue samples.

To narrow down their candidates, they focused on genes that could actually be targeted by medicines—not all genes are good drug targets. They identified 398 potential candidates this way. Finally, they tested their top 6 gene candidates in laboratory mice that were given sepsis-like infections to confirm their predictions were correct.

This approach is important because traditional drug development for sepsis is slow and expensive. By using genetic data to predict which genes matter, scientists can focus their efforts on the most promising targets. The mouse experiments add credibility by showing the genetic predictions actually match what happens in living organisms with sepsis

Strengths: The study used large, well-established genetic databases representing hundreds of thousands of people, which makes the genetic findings more reliable. The researchers validated their top candidates in mice, which is an important step. The study examined multiple types of genetic data (genes and proteins), providing a more complete picture. Limitations: The mouse studies involved a small number of animals and may not perfectly reflect human sepsis. The study is computational and experimental but hasn’t yet tested these findings in human patients. Some of the 34 potential drugs identified haven’t been tested for sepsis specifically

What the Results Show

The researchers’ main discovery was identifying 6 genes that appear strongly connected to sepsis: BCL6, PTX3, IL7R, BTN3A2, LGALS1, and HDC. Additionally, they found 21 proteins linked to sepsis risk. Some of these appear protective—meaning higher levels might help fight sepsis—while others appear harmful.

When they tested these genes in mice with sepsis-like illness, they found that three genes (BCL6, PTX3, and IL7R) were turned down (less active) in sick mice compared to healthy ones. Two genes (BTN3A2 and LGALS1) were turned up (more active) in sick mice. These patterns matched what the genetic analysis predicted, which strengthens confidence in the findings.

The researchers also identified 34 potential drugs that might target these genes. Some of these drugs already exist for other diseases, which means they could potentially be tested for sepsis treatment. The genes appear to work through immune system pathways and inflammation control—two critical problems in sepsis.

The study found that some of these genes are also connected to other serious conditions. For example, BTN3A2 appears linked to diabetes complications, while IL7R, BCL6, and PTX3 seem connected to vitamin D deficiency and cancer. This suggests these genes might be important for multiple diseases, not just sepsis. The analysis of biological pathways showed that the genes work through immune regulation and a pathway called FoxO signaling, which controls cell survival and stress responses

This research builds on previous work showing that immune system dysfunction is central to sepsis. Earlier studies identified inflammation as a key problem, and this work confirms that finding while pinpointing specific genes involved. The genes identified (like IL7R and BCL6) have been studied in other immune diseases, so researchers already know something about how they work. This study connects that existing knowledge to sepsis specifically

The mouse experiments used a specific type of sepsis model (cecal ligation and puncture) that may not represent all types of human sepsis. The study identified potential drug targets but hasn’t tested whether these drugs actually work in sepsis patients. Some genes showed only modest associations with sepsis risk. The research is based on genetic associations, which don’t always prove cause-and-effect relationships. The 34 potential drugs identified need further testing to determine safety and effectiveness

The Bottom Line

This research is preliminary and should not change current sepsis treatment. Doctors should continue using proven sepsis treatments (antibiotics, fluids, supportive care). This work may eventually lead to new medicines, but that’s years away. Patients with sepsis should follow their doctor’s current treatment recommendations. Researchers should prioritize testing the 34 identified drugs in laboratory and animal studies before any human trials

This research matters most to sepsis researchers and pharmaceutical companies developing new treatments. It’s relevant to doctors who treat sepsis patients, as it may eventually improve treatment options. People at high risk for sepsis (those with weakened immune systems, elderly patients, or those with serious infections) should know that better treatments are being researched. This is NOT immediately actionable for patients or the general public

If these findings lead to new drugs, the typical development timeline is 5-10 years before human testing begins, and another 5-10 years for approval. Realistic expectations: incremental improvements in sepsis treatment over the next decade, with possible new drug options becoming available in 10-15 years

Want to Apply This Research?

  • For sepsis survivors or high-risk individuals: Track immune system markers if available through medical testing (white blood cell counts, inflammatory markers like CRP). Monitor recovery milestones post-sepsis (energy levels, infection frequency, hospital readmissions) to identify patterns
  • Users at risk for sepsis should use the app to: (1) Track infection symptoms early (fever, rapid heartbeat, confusion) to enable quick medical attention, (2) Monitor vaccination status and schedule recommended vaccines, (3) Log antibiotic use and follow-through to completion, (4) Track lifestyle factors that support immune health (sleep, nutrition, stress)
  • Long-term tracking for sepsis survivors: Monitor recovery progress through symptom logs and functional capacity assessments. Track any new infections or concerning symptoms. Maintain records of all medical visits and test results related to sepsis recovery. Share this data with healthcare providers to identify patterns and optimize personalized recovery plans

This research identifies potential drug targets for sepsis but has not yet resulted in new approved treatments. Current sepsis treatment should not change based on this study. If you or a loved one has sepsis, follow your doctor’s treatment recommendations immediately—sepsis is a medical emergency. This research is in early stages and may take many years to translate into clinical practice. Do not delay seeking emergency medical care for suspected sepsis while waiting for new treatments. Always consult with your healthcare provider before making any changes to sepsis treatment or prevention strategies.