Scientists turn probiotic bacteria into tiny drug factories for pancreatic cancer

Cancer immunotherapy has dramatically changed how doctors treat many forms of cancer, yet pancreatic cancer has remained particularly resistant to these advances. A major obstacle is the environment that develops around pancreatic tumors. These tumors often create a "cold" tumor microenvironment that blocks immune cells from launching an effective attack.

Researchers at the University of Chicago have now developed a new approach that could help overcome this problem. In a study published in Science Advances, the team used BifidoSumIL-2, an engineered strain of Bifidobacterium longum, a probiotic bacterium naturally found in the gut, to carry an immune-stimulating treatment directly into tumors.

In animal models, the therapy slowed the growth of pancreatic tumors by selectively activating T cells that fight cancer. Its effects became even stronger when researchers combined it with chemotherapy, radiotherapy or immunotherapy. The findings suggest that BifidoSumIL-2 could eventually provide a new way to improve how pancreatic tumors respond to treatment.

Using Bacteria to Deliver Cancer Therapy

"A big unmet medical need has been pancreatic cancer, and so that was going to be our mountain to climb," said Ralph Weichselbaum, MD, the Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at the University of Chicago.

BifidoSumIL-2 was created to release a modified version of interleukin-2 (IL-2) once it reaches a tumor. IL-2 is a potent immune signaling molecule that activates T cells involved in attacking cancer. Conventional IL-2 treatment, however, can produce serious side effects and can also stimulate immune cells that actually weaken the antitumor response.

The researchers sought to avoid these problems by using SumIL-2, a modified form of IL-2 engineered to more precisely activate cancer-fighting T cells while reducing stimulation of regulatory T cells. They then placed SumIL-2 inside Bifidobacterium longum so that the therapeutic molecule could be concentrated within tumors instead of throughout the body.

Developing the treatment required scientists from several disciplines to work together, including specialists in microbiology, synthetic biology, oncology, and immunology.

"This was a highly interdisciplinary effort," said Mark Mimee, PhD, Assistant Professor of Microbiology at the University of Chicago. "We had to bring together people who understand bacteria, people who understand tumors, and people who understand the immune system to make something like this possible."

Why Bifidobacterium Can Target Tumors

Bifidobacterium offered the researchers an unusual advantage as a delivery system. The bacterium grows in anaerobic environments, meaning places with very little oxygen. Low oxygen levels are common inside many solid tumors, including pancreatic tumors, while healthy tissues generally contain more oxygen and are therefore less suitable for the bacteria.

"Bifidobacterium is an obligate anaerobe, so it doesn't grow in the presence of oxygen," Mimee said. When the bacteria are injected systemically, they are cleared from healthy tissues with abundant oxygen. Inside the low-oxygen regions of tumors, however, they can become active.

That preference allows the engineered bacteria to function as microscopic drug factories inside tumors. Once there, they produce SumIL-2 where the treatment is needed rather than broadly throughout the body. Researchers also noted that Bifidobacterium has shown a favorable safety profile in preclinical models and is already well known as a probiotic organism. It is commonly present in yogurt and is generally recognized as a safe, off-the-shelf probiotic.

Engineering the organism was not simple.

"Bifidobacterium is not the easiest organism to work with," Mimee said. "It's anaerobic, it grows slowly, and the genetic tools for manipulating it are much more limited compared to model bacteria like E. coli. A lot of the work was just figuring out how to reliably engineer it."

Stronger Results With Combination Treatments

Tests in animal models showed that BifidoSumIL-2 preferentially gathered inside tumors, stimulated immune activity, and slowed the growth of pancreatic cancer. It also changed the tumor microenvironment in a potentially beneficial way by increasing the activity of cancer-fighting CD8+ T cells.

The results improved further when BifidoSumIL-2 was paired with established cancer treatments. Combining the bacterial therapy with chemotherapy, radiation therapy, or anti-PD-L1 immunotherapy led to better tumor control and longer survival than the individual treatments achieved on their own.

"This combination potential is one of the study's most important findings; BifidoSumIL-2 not only works by itself -- it works with radiotherapy, chemotherapy, and immunotherapy," Weichselbaum said.

Despite the encouraging findings, BifidoSumIL-2 has not been tested in humans. Future research will need to examine its long-term safety, the possibility of effects outside the intended tumor, how long the immune response lasts, and whether the bacteria might eventually be given orally instead of through injection. The researchers also want to investigate whether the strategy can be combined with newer pancreatic cancer treatments, including KRAS inhibitors.

The Growing "Bugs as Drugs" Approach

The research adds to growing interest in a strategy known as "bugs as drugs." By engineering probiotic bacteria to seek out tumors and produce therapies directly inside them, scientists may be able to concentrate powerful immune treatments where they are most useful while reducing unwanted effects elsewhere in the body.

The study, "Engineered probiotic Bifidobacterium for tumor-targeted pancreatic cancer therapy" was supported by funds from the Ludwig Foundation and the National Institutes of Health.

Additional authors include Jaehyun Lee, Kaiting Yang, Christina Nowicki, Wei Liu, Emile Naccasha, and Hua Liang from the University of Chicago; Zhichen Sun from the University of Texas Southwestern, Dallas; and Yang-Xin Fu from Tsinghua University, Beijing, China.

UChicago Medicine and the Biological Sciences Division continue to be at the forefront of cancer care and research. In April 2027, UChicago Medicine will open the AbbVie Foundation Cancer Pavilion, Chicago's first freestanding cancer pavilion, to bring advanced diagnostics, innovative treatments, translational discoveries, and comprehensive support to patients and the community.

Journal Reference:

1. Jaehyun Lee, Kaiting Yang, Christina A. Nowicki, Wei Liu, Kangdi Li, Emile Naccasha, Zhichen Sun, Yang-Xin Fu, Hua Liang, Ralph R. Weichselbaum, Mark Mimee. Engineered probiotic Bifidobacterium for tumor-targeted pancreatic cancer therapy. Science Advances, 2026; 12 (30) DOI: 10.1126/sciadv.adz1388

Courtesy:

University of Chicago Medical Center. "Scientists turn probiotic bacteria into tiny drug factories for pancreatic cancer." ScienceDaily. ScienceDaily, 19 August 2026. <www.sciencedaily.com/releases/2026/08/260816044830.htm>.

 

 

 

 

 

 

Coffee drinkers have less fat, more muscle, and surprising hormone differences

Coffee is consumed around the world every day, and earlier research has associated coffee drinking with a reduced risk of conditions including type 2 diabetes and cardiovascular disease. Scientists still do not fully understand the biological processes that might explain those connections. Now, new research from Finland suggests that regular coffee consumption is associated with healthier body composition, favorable metabolic markers, and distinct patterns involving sex hormones in men and women.

Researchers at the University of Oulu analyzed information from 2,264 people who were 46 years old and taking part in the Northern Finland Birth Cohort 1966. The team investigated how participants' usual coffee intake related to circulating metabolites, indicators of cardiometabolic risk, and sex hormone levels.

Coffee Drinkers Had Less Fat and More Muscle

People who consumed more coffee tended to have lower levels of both total body fat and visceral fat, along with greater skeletal muscle mass. These differences appeared even though participants with higher and lower coffee intake had a similar body mass index (BMI).

Higher coffee consumption was also associated with lower circulating concentrations of branched-chain amino acids in both men and women. When chronically elevated, these biomarkers have previously been associated with insulin resistance and a greater risk of developing type 2 diabetes.

Coffee Intake Was Linked to Different Hormone Patterns

Some of the clearest differences appeared among men. Greater coffee consumption was associated with a more favorable glucose-insulin profile, higher levels of total and bioavailable testosterone, and greater concentrations of sex hormone-binding globulin (SHBG). However, free testosterone and the free androgen index were modestly lower.

The hormonal associations were less extensive in women. Higher coffee consumption was mainly associated with increased SHBG and lower measures of free androgens.

"Coffee is consumed by millions of people every day, yet we still know surprisingly little about how it relates to our metabolism and hormones. What stood out in our findings was a distinct hormonal signature that didn't disappear even after we took into account BMI and lifestyle factors, with several of these associations differing between men and women," says Luca Verroest, lead author of the study and Doctoral Researcher at the University of Oulu.

Hormones Could Offer a Clue to Coffee's Health Links

The findings raise the possibility that hormonal pathways could help explain some of the previously observed relationship between coffee consumption and metabolic health. Because the research was observational, however, it cannot establish that drinking coffee directly caused any of the biological differences identified in the study.

The setting also makes the research especially relevant. Finland ranks among the world's highest coffee-consuming countries, with average annual consumption of approximately 11.8 kilograms (26 pounds) per person.

Researchers say the results offer a starting point for studies designed to determine whether coffee itself produces these biological changes and, if so, which compounds may be responsible. Scientists are currently investigating these questions using animal models, with the longer-term aim of moving toward human intervention studies.

Additional research will be necessary before the findings can be used to shape dietary recommendations.

The study, "Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland Birth Cohort 1966 study," was published in the European Journal of Nutrition.

 

Journal Reference:

1. Luca Verroest, Jari Jokelainen, Shalini Choudhary, Jaroslaw Walkowiak, Toni Karhu, Saranya Palaniswamy, Juha Auvinen, Marjo-Riitta Jarvelin, Karl-Heinz Herzig, Ghulam Shere Raza. Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland birth cohort 1966 study. European Journal of Nutrition, 2026; 65 (5) DOI: 10.1007/s00394-026-04038-z

Courtesy:

University of Oulu, Finland. "Coffee drinkers have less fat, more muscle, and surprising hormone differences." ScienceDaily. ScienceDaily, 19 August 2026. <www.sciencedaily.com/releases/2026/08/260819041228.htm>.