Key Points:
- The study showed that aged mice develop a leaky gut as demonstrated with an intestinal barrier permeability experiment.
- Aged mice showed a deficiency in intestinal stem cell (ISC) metabolic function, yet short-term fasting restored their ISC metabolic function.
- From a functional perspective, fasting reversed intestinal leakage in young and old mice.
The intestines serve as a vital component of the digestive system, with critical functions in digestion and nutrient absorption. They also work as a barrier between the gut and the circulatory system, preventing harmful substances and bacteria from entering the blood and, ultimately, the organs.
Degenerative changes to the intestines with age lead to gastrointestinal disorders, resulting in absorptive deficiencies and the unregulated entry of intestinal contents into circulation. This circumstance can instigate age-related malnutrition and low-grade systemic inflammation (known as inflammaging), potentially exacerbating processes related to aging. As such, some researchers have proposed nutritional interventions, namely dietary regimens with lowered calorie intake, to improve intestinal function and counteract aging. While some research has suggested that short-term fasting can promote intestinal tissue restoration and longevity, how it does so has remained unclear.
To address this lack of clarity, Guo and colleagues from China Agricultural University published findings in Aging Cell showing that a form of short-term fasting reverses a leaky gut in aged mice. Furthermore, their study provides data suggesting that intermittent fasting promotes the cell power-generating mitochondrial function of ISCs. These findings support that fasting can improve the functional capacity of ISCs and alleviate a leaky gut, possibly adding depth to our understanding of fasting’s pro-longevity effects. If the findings translate to humans, they could mean that some forms of short-term fasting may aid against an aging gut.
In their study, Guo and colleagues used a type of intermittent fasting called alternate-day fasting. In that regard, the mice they used underwent a feeding routine where they did not consume food every other day and ate a standard diet on the other days. Humans who try alternate-day fasting typically use a similar, modified strategy where they eat a restricted diet, consuming only about 500 calories, every other day and then eating their standard diet other days.
Alternate-Day Fasting Restores a Leaky Gut
Because previous research suggests that the intestinal barrier becomes dysfunctional with age across species, from flies to mice, Guo and colleagues tested whether intestinal barrier leakage underlies this dysfunction in old mice. For their testing, the researchers removed a part of the intestines from mice, tied a knot at each end, and injected it with a fluorescent dye. Then, the China-based researchers measured the fluorescence of the solution surrounding the intestines as a way to assess the leakage of the dye from the intestines.
As expected, Guo and colleagues found that the fluorescent dye concentration in the fluid surrounding the small intestines nearly doubled in aged, 28-month-old mice (comparable to 77-year-old humans) compared to young mice. This finding suggests that intestinal leakage nearly doubles in old age, which could allow harmful substances and bacteria to enter circulation from the gut.
ISCs differentiate to become various cell types in the tissue lining the intestines. Thus, ISC dysfunction may underlie age-related intestinal barrier dysfunction and leakage. Due to this possibility, Guo and colleagues performed gene activity analyses in ISCs to identify what pathways may go awry with age in ISCs.
Interestingly, they found that aged ISCs were associated with metabolic alterations. Most notably, these metabolic alterations were reliant on mitochondrial energy metabolism.
Hence, Guo and colleagues tested how much cell energy, in the form of the energy molecule ATP, ISCs from aged mice produce. Compared to young mice, ISCs from older mice produced significantly less ATP. This finding suggests that metabolic alterations and lower ATP production from ISC mitochondria play a role in intestinal barrier dysfunction.
To find whether alternate-day fasting restores ISC metabolism, Guo and colleagues measured ISC ATP production after undergoing alternate-day fasting for eight weeks. They found that older mice showed significantly higher ISC ATP production following the eight-week alternate-day fasting protocol. However, young mice did not exhibit increased ISC ATP production following alternate-day fasting. These results suggest that, at least in older animals, alternate-day fasting improves ISC cell energy production and, thus, metabolism.
Because data from the study showed that the intestinal barrier becomes dysfunctional and leaks with age, Guo and colleagues next sought to find whether alternate-day fasting restores the intestinal barrier. They found that in aged mice and young mice, alternate-day fasting more than cut intestinal barrier leakage in half. However, alternate-day fasting’s effects on lowering intestinal barrier leakage were most significant in old mice. This finding supports that alternate-day fasting can improve the function of the intestinal barrier in both young and old mice but that the effect is greatest in old mice.
Consulting a Physician Before Engaging In Intermittent Fasting
Intermittent fasting may serve as a way to rejuvenate the intestinal barrier’s function and reverse leakage, as this study done with mice suggests. Performing a similar study with humans would be quite difficult, requiring biopsies of intestinal tissue. Furthermore, there is currently no definitive test to assess intestinal barrier leakage in humans, making a similar human study nearly impossible. Hence, this study provides some of the best data to suggest that a form of intermittent fasting, alternate-day fasting, improves intestinal barrier function.
One question that arises based on the study’s data is how ISC metabolism and intestinal barrier function improve with alternate-day fasting. Along those lines, researchers from UC San Diego have proposed that the pancreas secretes digestive enzymes following meals, which degrade biomolecules in the gut to instigate intestinal barrier leakage. In turn, prolonged periods without food, as with intermittent fasting, could allow the intestinal barrier more time to recover from digestive enzyme exposure. In that sense, longer periods without food, as with alternate-day fasting, could lead to less degradation of ISCs, enhance ISC cell energy production, and improve intestinal barrier function.
As for other research on intermittent fasting, a study presented at an American Heart Association conference in March 2024 claimed that a form of intermittent fasting, going eight hours a day without eating, is linked to a higher risk of death from heart disease. If the association between intermittent fasting and a higher risk of death from heart disease has merit, considering dietary alterations instead of practicing intermittent fasting may be a better means to preserve the gut. Accordingly, limiting processed foods that have been canned or which contain preservatives as well as reducing dietary fats may be ways to preserve your gut.
Before practicing any form of intermittent fasting, it is always best to consult with a physician. This may especially be the case in light of the research linking intermittent fasting to an increased risk of death from heart disease.
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