One day, bottles of probiotics might do more than keep you regular — they could help prevent disease. To get there, a $2 million grant to UC Riverside will explore how gut bacteria shape human health.
Beyond your DNA and your lifestyle, your microbes play a huge role in shaping how your body reacts to illnesses and vaccines.”
Ansel Hsiao, associate professor in UCR’s Department of Microbiology and Plant Pathology and principal investigator of the grant
The award from the National Institutes of Health (NIH) will support Hsiao’s lab in its quest to answer questions about how gut microbes communicate with each other and with their human hosts to influence health, or lack thereof.
Probiotics currently sold in markets can have beneficial effects on regularity and bloating. However, their effects are limited, in part because they don’t last long in the gut.
“Though commercial probiotics are regarded as safe, they do not make people resilient to disease,” Hsiao said. “They stick around for a day, maybe two. So, their beneficial effects rely on regular consumption.”
With a better understanding of microbes’ communication and behavior, Hsiao hopes his lab will one day create the next generation of probiotics and prebiotics that strengthen the gut microbiome, improve the effectiveness of vaccines, and prevent or lessen the severity of infections.
“One thing we can improve on with changing the gut microbiome, is making positive changes that last for extended periods of time,” Hsiao said.
Bacteria are individual cells that operate independently, but they can produce chemical signals that other cells can sense, and that might influence the behavior of another bacterial cell. This is called quorum sensing, which is the idea that you can have many individuals cooperating on a single goal.
“It’s like a company that requires a certain number of people to conduct a meeting. You have to have a quorum for the meeting to proceed,” Hsiao said. “Same idea with bacteria.”
When many bacteria in the same host are making enough communication molecules, the whole population of individuals can behave almost like a multi-cellular organism. Some pathogenic bacteria, like the diarrheal disease cholera, use this type of communication to coordinate their activity and optimize their interactions with the host during infection. When it’s multiplied to a high enough level, cholera bacteria signal to one another that it’s time to move on to a new host.
In collaboration with clinical teams in Bangladesh, Hsiao’s lab is also identifying bacterial profiles that correlate with stronger or weaker vaccine responses for diseases like cholera. By sequencing the gut bacteria present when a person is vaccinated, the team is beginning to predict who naturally develops immunity and who may need additional protection.
Though the cholera research is funded separately, the work could help explain why a cholera vaccine that’s 99% effective in the U.S. drops to about 50% effectiveness in parts of South Asia. Understanding the molecular mechanisms that connect gut bacteria with each other and to the host’s immune responses could extend the work from cholera to other diseases as well.
To probe these links under controlled conditions, Hsiao’s team uses germ-free mice. These animals are raised without any bacteria or fungi. By introducing specific microbes, researchers can connect specific microbes to specific health outcomes.
“It’s a powerful setup,” Hsiao said. “We can see how a vaccine or disease-causing microbe performs when the gut contains only one bacterial species, or when it resembles a real human microbiome.”
Some microbial differences are shaped by family or early-life exposure, but others come down to timing. The first bacteria to colonize a person’s guts can determine whether new species are welcomed or excluded, a dynamic known as the priority effect. This level of variability makes standardized medical approaches more complicated. Even a widely used probiotic strain might benefit one person but do nothing for another.
The recent NIH grant enables long-term investigations into how individualized microbial ecosystems affect health, not just in response to vaccines, but in other areas including cognition, nutrition, and diarrheal infection.
“This kind of support is not tied to one project but to the broader questions we’re pursuing,” Hsiao said. “And the questions are urgent. If we can understand how to work with the microbiome instead of against it, we can transform public health.”
Source:
University of California – Riverside