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Research Highlights
- Publish Date：2026-04-12
NYCU Study Identifies Key Gene Linking Gut Microbiota, Circadian Rhythm, and Metabolic Disease
The gut is not only a digestive organ—it also influences systemic metabolism and immune function through the “gut–liver axis.”
Edited by Chance Lai
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A research team at National Yang Ming Chiao Tung University (NYCU) identified a key gene, Nfil3, that regulates liver immunity and metabolism under high-fat diet stress, offering new insights into fatty liver disease, obesity, and related disorders.
Building on this discovery, the team led by Assistant Professor Li-Ling Wu of NYCU’s Institute of Physiology and Microbiota Research Center published their findings in the Journal of Translational Medicine.
A Molecular Switch in the Gut–Liver Axis
Expanding on these insights, Wu’s team demonstrated that Nfil3 is a critical regulator within the so-called “gut–liver axis,” a biological pathway through which the gut microbiota communicates with the liver to influence systemic metabolism and immune responses.
“The gut is not just a digestive organ—it is a central hub of the immune system,” Wu said. “When the gut is out of balance, the effects extend far beyond digestion, impacting the entire body.”
Modern lifestyle factors—like high-fat diets and irregular sleep—destabilize this system. The study finds that Nfil3 integrates signals from both diet and disrupted biological clocks, shaping the body’s response to metabolic stress.
Gene Deletion Reduces Obesity and Liver Fat
In experimental models, the researchers observed that removing Nfil3 led to striking metabolic improvements. Even when fed a high-fat diet, mice lacking the gene showed reduced weight gain, more stable blood glucose levels, and lower liver fat accumulation.
These results highlight Nfil3's active role in promoting obesity and fatty liver disease when the body faces metabolic stress.
Probiotics Show Similar Protective Effects
The study found a promising therapy: multi-strain probiotics, such as VSL#3, improved gut microbiota—boosting good bacteria and reducing those linked to inflammation.
Building on this discovery, the team led by Assistant Professor Li-Ling Wu of NYCU’s Institute of Physiology and Microbiota Research Center published their findings in the Journal of Translational Medicine.
A Molecular Switch in the Gut–Liver Axis
Expanding on these insights, Wu’s team demonstrated that Nfil3 is a critical regulator within the so-called “gut–liver axis,” a biological pathway through which the gut microbiota communicates with the liver to influence systemic metabolism and immune responses.
“The gut is not just a digestive organ—it is a central hub of the immune system,” Wu said. “When the gut is out of balance, the effects extend far beyond digestion, impacting the entire body.”
Modern lifestyle factors—like high-fat diets and irregular sleep—destabilize this system. The study finds that Nfil3 integrates signals from both diet and disrupted biological clocks, shaping the body’s response to metabolic stress.
Gene Deletion Reduces Obesity and Liver Fat
In experimental models, the researchers observed that removing Nfil3 led to striking metabolic improvements. Even when fed a high-fat diet, mice lacking the gene showed reduced weight gain, more stable blood glucose levels, and lower liver fat accumulation.
These results highlight Nfil3's active role in promoting obesity and fatty liver disease when the body faces metabolic stress.
Probiotics Show Similar Protective Effects
The study found a promising therapy: multi-strain probiotics, such as VSL#3, improved gut microbiota—boosting good bacteria and reducing those linked to inflammation.
The metabolic effects of probiotic supplementation resembled those observed in Nfil3-deficient models.
“This indicates that gut microbes can remotely regulate systemic metabolism through this key pathway,” Wu explained.
Toward Precision Treatment of Metabolic Disease
This research reveals that gut microbiota, circadian rhythms, and immune metabolism connect through Nfil3, advancing our understanding of metabolic disease mechanisms.
Wu described Nfil3 as a master "control switch" that integrates both dietary and biological clock signals to affect health.
Looking ahead, she said, the treatment of metabolic diseases may move beyond conventional dietary interventions toward more precise strategies that target the gut microbiota and restore healthy biological rhythms.
“Future therapies will focus on how to rebalance the body’s internal ecosystem,” Wu said, “and regain control over metabolic health.”
Assistant Professor Li-Ling Wu (front row, center) and her research team.Related Image(s)：
