The concept of bacterial cancer therapy dates back to 1868, when German physician Busch reported that a cancer patient deliberately infected with bacteria later experienced remission. In 1893, Dr. William Coley further advanced this idea by developing bacterial-based treatments, paving the way for modern immunotherapies such as checkpoint inhibitors and CAR-T cell therapies.

While these treatments have transformed cancer care, they share a major drawback: they depend heavily on the immune system. For patients whose immunity is weakened by chemotherapy or radiotherapy, such therapies often fail to work effectively.

AUN: Two Bacteria in Perfect Balance

The newly developed AUN therapy directly overcomes this limitation. It is made up of two naturally occurring bacterial species:

• Proteus mirabilis (A-gyo), a bacterium that naturally resides in tumors
• Rhodopseudomonas palustris (UN-gyo), a photosynthetic bacterium

Together, these bacteria act in harmony to destroy cancer cells in both animal and human models. Remarkably, they succeed even when immune function is impaired. AUN has shown strong compatibility with the human body and few side effects, including suppression of cytokine release syndrome (CRS), a potentially dangerous immune reaction.

How AUN Works to Eliminate Tumors

The AUN consortium achieves its tumor-fighting power through a series of coordinated mechanisms:

• Precisely targeting and destroying tumor blood vessels and cancer cells
• Undergoing a structural transformation in A-gyo (filamentation) triggered by tumor-specific metabolites, which enhances its ability to kill cancer cells
• Adjusting the bacterial ratio inside the tumor environment, shifting from an initial mix of roughly 3:97 (A-gyo to UN-gyo) to about 99:1, maximizing its therapeutic strength
• Reducing toxicity and minimizing side effects, including avoidance of CRS

Harmony Between Opposites

UN-gyo only becomes active and beneficial when paired with A-gyo, serving as a regulator that curbs harmful bacterial activity while increasing their cancer-killing precision. This mutual cooperation embodies the Japanese concept of "AUN," symbolizing balance and harmony between opposites. It is this finely tuned relationship that gives the therapy its exceptional results, achieving what traditional immune-dependent treatments could not.

Toward Clinical Trials and a New Era in Cancer Therapy

"We are preparing to launch a startup to advance this technology and hope to begin clinical trials within six years," explained Professor Miyako. "A new chapter in bacteria-based cancer therapy -- pursued for over 150 years -- is finally beginning."

This groundbreaking method marks a turning point for cancer patients with weakened immune systems. It offers a long-sought option where conventional immunotherapies fall short, signaling the arrival of truly immune-independent cancer treatment.

The findings have been published in Nature Biomedical Engineering.

RELATED STORIES

The protocol emphasized the immediate start of dialysis as soon as MALA was identified, using one of three methods: intermittent hemodialysis, continuous kidney replacement therapy, or peritoneal dialysis. The program was introduced at Maharat Nakhonratchasima Hospital (MNRH) in Thailand, while Burirum Hospital (BH) served as a comparison site and continued standard care without the new approach.

Over a five-year study period, the researchers analyzed 347 total cases (70 at MNRH before the protocol, 129 after the protocol, and 148 at BH).

Major Reductions in Deaths and Faster Treatment

Results showed striking improvements at Maharat Nakhonratchasima Hospital. The 30-day death rate fell from 25.7% before the new system to 13.9% afterward. At Burirum Hospital, which did not adopt the protocol, mortality rates remained unchanged (27.2% and 30%).

The ongoing data at MNRH showed a steady decline in deaths, dropping by 2.08% per quarter throughout the intervention period. Average "door-to-dialysis" time -- the time between a patient's hospital admission and the start of dialysis -- was shortened from 870 minutes to 690 minutes. Awareness of MALA among medical staff also rose dramatically, from 38.5% to 89.9% after implementation.

Faster Response, Greater Awareness, and Better Outcomes

"A standardized MALA protocol covering diagnosis, access, and treatment shortened door-to-dialysis time, increased awareness, and reduced care variation," said corresponding author Watanyu Parapiboon, MD, of Maharat Nakhon Ratchasima Hospital in Thailand. "Fast-track dialysis pathways should be adopted for time-sensitive conditions like MALA. Availability of all dialysis modalities ensures flexibility and enables timely treatment initiation."

Study: "Reducing Mortality in Metformin-Associated Lactic Acidosis (MALA) Through a Fast-Track Clinical Pathway: A Controlled Interrupted Time Series Quality Improvement Study."

Metformin Overview

Metformin is one of the most commonly prescribed medications for managing type 2 diabetes. It works by improving the body's sensitivity to insulin, reducing the amount of glucose produced by the liver, and enhancing glucose uptake by muscle cells. The drug is well established for its effectiveness, affordability, and relatively low risk of causing low blood sugar. Beyond diabetes control, research has explored metformin's potential benefits in weight management, heart health, and even aging, although its primary role remains in helping people with type 2 diabetes maintain stable blood sugar levels.

Metformin-Associated Lactic Acidosis Overview

Metformin-associated lactic acidosis (MALA) is a rare but serious medical emergency in which lactic acid accumulates in the bloodstream due to the body's impaired ability to clear it while taking metformin. This condition can lead to dangerously low blood pH, muscle weakness, rapid breathing, confusion, and in severe cases, organ failure or death. MALA typically occurs in patients with underlying kidney problems, liver disease, or conditions that limit oxygen delivery to tissues. While extremely uncommon, it requires urgent diagnosis and immediate treatment -- often including dialysis -- to remove excess acid and prevent life-threatening complications.