Gastrointestinal (GI) complications, such as postoperative ileus (POI) and intra-abdominal infections (IAI), remain a major concern after radical cystectomy for bladder cancer. Even with advances in surgical techniques, including robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC), and the adoption of enhanced recovery protocols, these complications continue to affect a substantial proportion of patients. They not only prolong hospital stays but also increase patient morbidity, underscoring the need to identify risk factors beyond surgical technique alone.
In a new study published in Volume 15 of the journal Scientific Reports on July 1, 2025, a research team led by Associate Professor Kenji Zennami of Nagoya University School of Medicine and Fujita Health University School of Medicine, Japan, together with Professor Ryoichi Shiroki and Professor Kiyoshi Takahara of Fujita Health University School of Medicine, investigated the role of the gut microbiota in postoperative complications. The team examined fecal samples from the distal ileum and ascitic fluid from 146 patients who underwent iRARC without bowel preparation and with short-term antibiotic prophylaxis. They found that, although the ileal microbiota was largely suppressed by antibiotics in most patients, the persistence of intra-abdominal bacteria and fungi was strongly linked to GI complications.
“Although the distal ileal microbiota is usually sparse under short-term antibiotic prophylaxis, our findings show that the presence of residual intra-abdominal bacteria or fungi is strongly linked to GI complications,” says Dr. Zennami. “Frailty appears to exacerbate microbial imbalance, particularly with Enterococcus and Enterobacter species, and this contributes to postoperative risks.”
The results were striking. Patients with positive bacterial or fungal growth in their ascitic fluid had a more than six-fold higher risk of developing complications compared to those without. In fact, 72.5% of patients with positive ascitic cultures experienced POI or infection, compared with just 11.3% of those with negative cultures. Even the presence of bacteria in ileal feces alone was associated with nearly a four-fold increase in complications. Notably, all cases of IAI occurred in patients with both positive ileal and ascitic cultures, implicating residual microbes as a key driver of serious postoperative events.
Frailty emerged as a particularly important factor. Frail patients, identified using the Geriatric-8 questionnaire, were far more likely to harbor residual microbes and to develop complications than non-frail patients. While only 12% of non-frail patients experienced GI complications, the rate rose dramatically to 63% among frail patients. Moreover, frail individuals showed a distinctive microbial profile, with a greater prevalence of Enterococcus and Enterobacter, including carbapenem-resistant strains that were not observed in non-frail patients.
“Our study highlights that surgical techniques and perioperative protocols alone cannot fully prevent GI complications,” explains Dr. Zennami. “Frailty and gut microbiota play an equally important role, and addressing these factors may be essential for improving patient outcomes.”
These findings have several implications for clinical practice. Current guidelines for perioperative antibiotic prophylaxis in urology vary, and the study suggests that prophylactic regimens should be tailored to target organisms likely to persist in frail patients. Beyond antibiotics, the results also point to the potential of incorporating frailty assessment and prehabilitation programs—such as exercise and nutritional support—into surgical planning. Microbiota-based interventions, including probiotics and synbiotics, could also help reduce the risk of POI and infections by supporting a healthier gut environment before surgery.
While the study was conducted at a single center and relied on conventional culture methods, it provides some of the first direct evidence linking frailty-associated gut dysbiosis to adverse surgical outcomes in patients with bladder cancer. The researchers emphasize that larger, multicenter studies are needed to confirm these findings and to evaluate targeted interventions.
“In the future, we may see microbiota-based management become a standard component of perioperative care,” concludes Dr. Zennami. “By integrating frailty assessment with strategies that support a healthier gut environment, we have the potential to improve recovery, reduce complications, and tailor treatment for vulnerable patients.”
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Reference
DOI: 10.1038/s41598-025-07932-4
About Fujita Health University
Fujita Health University (FHU) is a private medical university located in Aichi, Japan. Established in 1964, it houses one of the largest university hospitals in Japan. It's 900 member faculty provides diverse learning and research opportunities to medical students worldwide. Guided by its founding philosophy of "Our creativity for the people" Fujita Health University believes that it's students can shape the future through creativity and innovation. FHU has earned global recognition, ranking eighth among all universities and second among private universities in Japan in the 2020 Times Higher Education (THE) World University Rankings. The university ranked fourth worldwide in the 2024 THE University Impact Rankings for contributions to the "Good Health and Well-being" SDG (Sustainable Development Goals) of the United Nations (UN). In June 2021, the university made history as the first Japanese institution to host the THE Asia Universities Summit. In 2024, Fujita Health University was awarded the Forming Japan’s Peak Research Universities (J-PEAKS) Program by the Japanese government to establish an innovative academic drug discovery ecosystem and hub of a multi-university consortium for research and education.
Website: https://www.fujita-hu.ac.jp/en/index.html
About Associate Professor Kenji Zennami from Fujita Health University
Associate Professor Kenji Zennami is a urologist at Nagoya University Hospital and Fujita Health University School of Medicine. He earned his M.D. (2004) and Ph.D. (2009) from Aichi Medical University and completed a postdoctoral fellowship in prostate cancer research at Johns Hopkins University (2015–2017). Over nearly two decades, he has published more than 60 peer-reviewed articles and holds active research grants in urology-related genomics and bladder cancer. His expertise spans robot-assisted surgeries—including radical prostatectomy, partial nephrectomy, cystectomy—and intracorporeal urinary diversion, with aims to standardize techniques and unravel cancer biology mechanisms.
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