UH Associate Professor Melissa Zastrow is investigating how essential trace metals alter the human gut microbiome and whether these changes directly trigger gastrointestinal disease.
The probiotic bacteria commonly found in grocery store yogurt may hold the key to understanding how everyday supplements and dietary metals shape human health, according to 91视频 researchers.
Backed by a new five-year, $2.19 million grant from the National Institutes of Health, UH Associate Professor Melissa Zastrow is investigating how essential trace metals alter the human gut microbiome and whether these changes directly trigger gastrointestinal disease.
Dietary metals such as zinc and iron are critical for human survival, but gut microbes also rely on them to function. When metal levels fluctuate 鈥� whether from daily multivitamins or nutritional deficiencies 鈥� the delicate balance between beneficial bacteria and illness-causing pathogens can destabilize. Despite this connection, scientists still cannot predict how shifts in diet alter microbial chemistry.
鈥淢etals impact the gut microbiota and correlate with various pathologies, but impacts are hard to predict and control because we do not understand all of their roles or how they are regulated between species and the host in the gut microbiota,鈥� said Zastrow, principal investigator of the grant. 鈥淢y research will yield insight into this knowledge gap and inform the development of new therapeutics while guiding the use of current therapeutics.鈥�
A New Path Forward
Tracking these interactions in living gut systems has long been an obstacle for scientists. Traditional biosensors, such as green fluorescent proteins derived from jellyfish, require oxygen to become fluorescent. Because the healthy human gastrointestinal tract is an anaerobic, low-oxygen environment, conventional optical sensors fail to function.
To overcome this, Zastrow re-engineered natural light-sensing proteins that do not rely on oxygen to glow. Rather than manufacturing physical, tabletop monitoring devices, her laboratory genetically modifies bacteria into living, self-assembling biosensor factories. When introduced into the bacteria, custom DNA instructs the microbes to produce fluorescent proteins that light up under a microscope. When these proteins bind to specific metals, this fluorescence is enhanced or reduced, enabling real-time biochemical tracking inside an oxygen-starved environment.
Building on an initial 2020 NIH award that proved these biosensors could detect zinc and copper, the new award funds the development of a comprehensive sensor panel. Zastrow鈥檚 team is engineering sensors that emit across multiple wavelengths 鈥� ranging from green to near-infrared 鈥� and expanding detection to include manganese and iron with varying binding affinities.
The team is focusing on Lactobacillus, a family of beneficial bacteria found in yogurt and probiotic supplements. While Lactobacillus species are known to be sensitive to metal fluctuations, their internal regulatory systems remain largely unmapped.
To study these microbes in a realistic setting without animal testing, Zastrow鈥檚 lab is using 3D-printed flow-cell cartridges developed with Texas Medical Center collaborators. These in-vitro models circulate nutrients to simulate bacterial competition in the human small intestine, where the body absorbs the majority of dietary metals.
By watching multiple bacterial species compete for nutrients in real time, Zastrow aims to move the medical field past simple correlations.
鈥淩ight now, a lot of the evidence connecting metal changes to gut disease is just correlation, not necessarily causation,鈥� Zastrow said. 鈥淯nderstanding how these bacterial communities handle changes in trace nutrients will eventually get us to the point of asking: Can somebody use this knowledge as a therapeutic approach to mitigate infection or chronic gut diseases?鈥�
Research reported in this press release is supported by the National Institute of General Medical Sciences of the NIH under award number R35GM161898.