Microbiome Rhythm & Metabolic Health
Engineered Gut Bacteria Shows Promise for Metabolic Health, Mimicking Time-Restricted Feeding Benefits
san Diego, CA - In a groundbreaking study, researchers at the University of California San Diego have engineered a native gut bacterium to continuously express an enzyme that mimics the metabolic benefits of time-restricted feeding (TRF), a dietary pattern known to improve metabolic health. This innovative approach holds the potential to offer a novel therapeutic strategy for common metabolic disorders like obesity and type 2 diabetes.
The research, led by Dr. Pandolfi Zarrinpar, focused on a specific enzyme, bile salt hydrolase (BSH), which plays a crucial role in bile acid metabolism. Bile acids are signaling molecules that influence various metabolic processes, including glucose and lipid regulation. By engineering a common gut bacterium, Bacteroides thetaiotaomicron, to continuously produce BSH, the team observed notable improvements in metabolic health in mice, even without the need for strict adherence to a TRF schedule.
“Our engineered bacterium continuously expressed the enzyme DnBSH1, independently of dietary or environmental factors,” explained Zarrinpar. “As an inevitable result, the bacterium provided metabolic benefits similar to those seen with TRF, even without requiring the mice to strictly adhere to a TRF schedule.” These benefits included improved insulin sensitivity and better blood glucose regulation.
The long-term vision for this research is to develop a therapeutic that can be administered as a single dose, stably colonize the gut, and provide lasting metabolic advantages. The next crucial step involves testing the engineered bacteria in obese and diabetic mice on a high-fat diet to validate its efficacy.If successful, this coudl pave the way for targeted therapies and interventions for prevalent metabolic disorders.
“This suggests the exciting possibility that this engineered microbe might serve either as a replacement for TRF or as a way to enhance its beneficial effects,” Zarrinpar added. “Further studies will help determine whether combining this ENB with TRF could provide additional or synergistic improvements in metabolic health.”
Expert Perspectives and future Directions
Dr. Mitchell Roslin, MD, FACS, a pioneer in bariatric surgery and professor at the Donald and Barbara Zucker School of Medicine, acknowledged the significance of the study. ”I agree that bile is very crucial in controlling metabolism and glucose,” he stated. “Using enzymes or medications that work in the GI tract without absorption into the body is very engaging and has great potential. It is an early but exciting prospect.”
However,Dr. Roslin also raised important considerations. “I think we are still trying to understand whether the difference in microbiomes is the cause or effect/association,” he commented. “Is the microbiome the difference or is a different microbiome representative of a diet that has more fiber and less processed foods? Thus, while I find this academically fascinating, I think that there are very basic questions that need better answers, before we look at the transcription of bacteria.”
Furthermore,translating findings from animal models to humans presents its own set of challenges. “Small animal research is mandatory,but how the findings convert to humans is highly speculative,” Dr.Roslin cautioned. “Mice that are studied are usually bred for medical research, with reduced genetic variation. Many animal models are more sensitive to time-restricted eating and caloric restriction than humans.”
Despite these caveats, the UC San Diego study represents a significant advancement in understanding host-microbe interactions. ”We demonstrate that host circadian rhythms substantially influence microbial function, and conversely, these microbial functions can directly impact host metabolism,” Zarrinpar concluded. “Importantly, we now have a method to test how specific microbial activities affect host physiology by engineering native gut bacteria.”
Dr.Roslin echoed the sentiment regarding the importance of continued research into the gut microbiome. “There is wider evidence that bacteria and microbes are not just passengers using us for a ride but perhaps manipulating every action we take.” This research underscores the profound influence of our gut’s microbial inhabitants on our overall health and opens new avenues for therapeutic innovation.