Turning back the clock on the microbiome is key to preventing liver cancer and aging, study finds

As rates of chronic digestive diseases continue to rise, researchers are increasingly turning their attention to the intestinal microbiome - and the vast community of bacteria living in the digestive tract - as a key indicator of long-term health.

Emerging evidence suggests that age-related changes in this microbial ecosystem may contribute to low-grade or chronic inflammation, liver dysfunction, and even cancer, raising the possibility that preserving or restoring a more youthful microbiome could help prevent serious conditions, including liver cancer, before they develop.

"Our research has shown that maintaining a healthy, more youthful digestive microbiome helps preserve heart and liver function, reduce inflammation, mitochondrial dysfunction, telomere shortening, and DNA damage, and may help prevent liver cancer from developing in animal models," said Qingjie Li, PhD, associate professor of medicine in the Division of Gastroenterology at The University of Texas Medical Branch (UTMB).

Li presented his findings at Digestive Disease Week (DDW) in Chicago in early May and was invited by the American Association for the Study of Liver Diseases (AASLD) to discuss the research during its presidential plenary lecture.

His study offers insight into how bacteria living in the digestive system may shape disease risk as people age. In his findings, Li tracked how the microbiome shifts over time and tested an unusual approach: collecting bacteria from young mice and transplanting it back to the same mice later in life.

The microbiome is evaluated through fecal samples and is typically more diverse - and therefore more stable and resilient - at a younger age. As it ages, it becomes less diverse and less resilient, and its anti-inflammatory function declines.

The results suggest those early-life microbes may help counter age-related changes linked to conditions including liver cancer, pointing to the microbiome as a potential target for future anti-aging therapies.

"We were very surprised because this is such a striking result," Li said. "Our model shows that preserving and reintroducing the youthful microbiome completely prevents liver cancer and rectifies many age-related changes in the liver."

Liver cancer, he said, is most common in people ages 70 and older.

"When you have a physical, your liver function is checked," he said. "They measure AST (aspartate aminotransferase) and ALT (alanine aminotransferase), which are key enzymes in blood tests used to detect liver disease. If these levels are high, as they were in the older animals we tested, that indicates poor liver function."

Maintaining a youthful microbiome significantly reduced those levels.

"We know these levels tend to increase with age, but this can be mitigated based on what we've learned," he said.

Low-grade and chronic inflammation also increase with age, but the transplant treatment significantly suppressed that response.

"It's possible to preserve your youthful microbiome when you're in your 20s or 30s through biomedical companies that store it," Li said. "Decades later, you can undergo a microbiome transplant using your own sample. Fecal microbiomes from young donors may work as well. The easiest method is capsule form, taken orally."

The digestive microbiome can also be transplanted using the same type of scope used during a colonoscopy or by enema.

Preserving the microbiome's youthful diversity is key to maintaining its health. Individuals can help support it by eating a balanced diet, maintaining a healthy weight, limiting alcohol consumption, and avoiding unnecessary antibiotic use, which can kill beneficial bacteria.

"All of those things really help, and it's important to understand how much a healthy, diverse digestive microbiome matters," Li said.

Researchers are continuing to explore how youthful and aging microbiomes differ, along with the beneficial bacteria that may help maintain diversity in the gut.

"We are a long way from that, but I am working to repeat these experiments in animals and secure funding for a clinical trial in humans," Li said. "This study shows the aging intestinal microbiome may actively contribute to liver dysfunction and cancer risk, but restoring a more youthful microbiome could reverse several core features of aging at the molecular and functional level."