A cancer patient experiencing weight loss. [AI-generated image]
A cancer patient experiencing weight loss. [AI-generated image]

Researchers have identified a new potential treatment approach for cancer cachexia — a life-threatening complication affecting many cancer patients — using the gut microbiome.

Cancer cachexia is a condition in which advancing cancer causes rapid loss of body weight and muscle mass, accompanied by systemic inflammation and metabolic dysfunction. In severe cases, it weakens patients' physical condition and immune function, making anticancer treatment more difficult and reducing survival rates.

A research team led by Kim Myung-seok and Lee Chung-gu at the Korea Institute of Science and Technology's Natural Product Efficacy Optimization Research Center announced Sunday that they had identified a natural compound candidate and its mechanism of action for improving cancer cachexia by regulating the gut microbial ecosystem.

The team screened a library of more than 4,000 natural compounds and confirmed that micheliolide (MCL) was effective in alleviating cancer cachexia.

When MCL was administered to animal models of colorectal and pancreatic cancer, muscle mass increased by 34% and muscle strength by 31%, with no significant effect on tumor size. Rather than directly attacking cancer cells, the compound suppressed the muscle wasting caused by cancer.

MCL restored T-cell function impaired by cancer and suppressed the secretion of inflammatory cytokines. The researchers concluded that an immune-regulatory mechanism was at work, reducing cancer-induced inflammation and preventing muscle breakdown.

The team also confirmed that MCL's effects were closely linked to the gut microbiome. In mice treated with antibiotics to eliminate gut bacteria, MCL showed no muscle-improving effect.

Kim Myung-seok (left) and Lee Chung-gu, researchers at the Korea Institute of Science and Technology who conducted the study. [Provided by KIST]
Kim Myung-seok (left) and Lee Chung-gu, researchers at the Korea Institute of Science and Technology who conducted the study. [Provided by KIST]

Analysis of the gut microbiome showed that MCL selectively increased levels of the beneficial bacterium Phocaeicola vulgatus. The research team then analyzed the metabolites produced by that bacterial strain and identified 11 new cyclopeptides that promote muscle synthesis and suppress inflammatory responses.

The study is significant for presenting a new treatment strategy that moves away from conventional anticancer approaches targeting cancer cells directly, instead modulating the gut microbiome and immune system to address cancer cachexia.

If developed into a natural compound-based oral treatment, the researchers said, it could help cancer patients undergoing anticancer therapy maintain their physical condition and quality of life, and potentially be used alongside existing anticancer drugs to enhance treatment outcomes.

"This research identified the potential to improve cancer cachexia through the interaction between natural compounds and the gut microbiome," Kim said. "Going forward, it will be possible to develop innovative host-directed therapeutics that preserve the physical condition and immune function of patients with intractable cancers, thereby improving the success rate of combination anticancer treatment."

The findings were published in the latest issue of the international journal Microbiome.


nbgkoo@heraldcorp.com