Gut Microbes Show How Eating Times Boost Metabolism

New Research Reveals Timing Your Meals Aligns Gut Bacteria for Better Health

When you eat could be as crucial as what you eat for metabolic well-being. Scientists are uncovering how synchronizing meal times with your gut microbes’ daily activity can offer significant health advantages.

Unlocking Microbial Rhythms

Researchers at UC San Diego have pioneered methods to observe real-time changes within the gut microbiome. Their goal was to determine if aligning eating schedules with peak microbial activity, a practice known as time-restricted feeding (TRF), could improve metabolic health.

Amir Zarrinpar, MD, PhD, a gastroenterologist and associate professor at UC San Diego School of Medicine, explained the study’s focus: Microbial rhythms are daily fluctuations in the composition and function of microbes living in our gut. Much like how our bodies follow an internal clock (circadian rhythm), gut microbes also have their own rhythms, adjusting their activities based on the time of day and when we eat.

The team specifically investigated whether TRF could counteract the negative metabolic effects commonly associated with high-fat diets.

Advancing Gut Science with Metatranscriptomics

A significant leap in this research was the adoption of metatranscriptomics. This advanced technique allows scientists to capture real-time microbial activity by analyzing RNA transcripts, offering a dynamic view of what microbes are doing, unlike older metagenomics methods that only identified potential capabilities.

Zarrinpar elaborated on the technology’s impact: It helps us understand not just which microbes are present, but specifically what they are doing at any given moment. In contrast, metagenomics looks only at microbial DNA, which provides information about what microbes are potentially capable of doing, but doesn’t tell us if those genes are actively expressed.

The instability of RNA previously made widespread metatranscriptomic analysis challenging. However, improved bioinformatics tools and decreasing sequencing costs are now making this powerful technology more accessible for in-depth research into microbial gene expression.

Key Findings: TRF Offers Metabolic Protection

In a study involving three groups of mice—one on an unrestricted high-fat diet, another on an 8-hour TRF high-fat diet, and a control group on a standard diet—compelling results emerged after eight weeks.

Mice consuming a high-fat diet without time restrictions exhibited metabolic dysfunction. This was linked to disrupted circadian and microbial rhythms, leading to increased daytime eating—a period when mice typically rest. This misalignment can negatively impact metabolism and overall health.

Conversely, mice on the high-fat diet within the TRF window were protected from adverse effects such as increased body fat, inflammation, and insulin resistance. They also showed improved glucose regulation and a partial restoration of daily microbial rhythms.

Engineering a Solution: The Power of Bile Salt Hydrolase

The study identified bile salt hydrolase (BSH), an enzyme crucial for lipid and glucose metabolism, as a pivotal factor in the observed metabolic improvements. Specifically, the gut microbe *Dubosiella newyorkensis* showed enhanced BSH gene expression during daytime feeding in the TRF group.

To test this, researchers engineered a benign gut bacterium to continuously express a BSH variant from *Dubosiella newyorkensis*. Mice receiving this engineered bacterium demonstrated increased lean muscle mass, reduced body fat, lower insulin levels, and better blood glucose control, mirroring benefits seen with TRF.

It is still early to know the full clinical potential of this new BSH-expressing engineered native bacterium. However, our long-term goal is to develop a therapeutic that can be administered as a single dose, stably colonize the gut, and provide long-lasting metabolic benefits. stated Zarrinpar, highlighting the potential for a one-time therapeutic intervention.

Expert Perspectives and Future Directions

Mitchell Roslin, MD, FACS, chief director of bariatric and metabolic surgery at Lenox Hill Hospital, who was not involved in the study, commented on the findings: Using enzymes or medications that work in the GI tract without absorption into the body is very interesting and has great potential. It is an early but exciting prospect.

However, Dr. Roslin also raised important questions: I think we are still trying to understand whether the difference in microbiomes is the cause or effect/association. Is the microbiome the difference or is a different microbiome representative of a diet that has more fiber and less processed foods? He also noted that translating findings from mice to humans can be speculative.

This research underscores the intricate link between host circadian rhythms and microbial functions, impacting host metabolism. The development of engineered bacteria offers a promising avenue for future targeted therapies against metabolic disorders, potentially offering benefits similar to dietary timing strategies.