University of California San Diego researchers have developed a new tool for understanding and modifying any microbiome, including the human microbiome. The approach, called Microbial Interaction and Niche Determination (MIND), accurately predicts how microbes compete within complex communities and identifies their specific nutrient preferences.
The findings, published in Cell, have the potential to accelerate the translation of microbiome science from the lab to the clinic, paving the way for highly targeted microbiome therapies.
MIND analyzes how microbes allocate their finite resources to translating messenger RNA (mRNA) into functional proteins, a cell’s most energy-intensive process. By measuring which specific proteins a microbe is actively making at any given time using a technique called ribosome profiling, the tool reveals which exact nutrients it prefers and how it allocates its energy.
If two different types of bacteria prefer the same nutrients, MIND flags them as competitors. By applying this approach to thousands of microbes, the researchers can map out complex competitive interactions and predict how communities will respond when species are added or removed.
Armed with this map, the researchers tested these predictions by introducing specific nutrients like sugars and amino acids to selectively feed and boost certain microbes, allowing them to outcompete others and reshape the microbial community in several environments:
- Synthetic Microbial Communities: In a 16-member microbial community, MIND accurately predicted competitive interactions and identified which specific microbes would benefit from the addition of particular substrates.
- Soil Microbiomes: MIND accurately predicted which nutrients would boost beneficial bacteria and naturally crowd out their competitors.
- Human Microbiomes: The tool identified the preferred nutrients of beneficial infant gut bacteria like Bifidobacterium, guiding precise and probiotic interventions that selectively promoted target bacteria while suppressing competitors.
- Live Mouse Model: MIND predicted that a beneficial gut bacterium, Faecalibaculum rodentium, would thrive in the presence of lactose. Supplementing mice with lactose selectively enriched this bacterium, demonstrating that the method works safely and precisely in a living animal.
The findings have major implications for treating infectious diseases by enabling rapid, cost-effective and precise prebiotic interventions. For example, many healthy adults naturally carry potentially dangerous bacteria like Clostridioides difficile or Staphylococcus aureus without ever getting sick because beneficial microbes keep them in check. Using MIND to identify these natural competitors could allow clinicians to administer prebiotics that lower pathogen levels just enough to prevent an infection. This offers an additional approach beyond the use of broad-spectrum antibiotics, which destroy beneficial bacteria and drive antibiotic resistance.
Because MIND relies on manipulating naturally occurring microbes rather than developing new drugs, these therapies would be more cost-effective, face fewer regulatory hurdles and could reach the clinic more quickly.
Data from UCSD