NewsMakers
Diet, gut microbes affect cancer treatment outcomes, research suggests
What we eat can affect the outcome of chemotherapy – and likely many other medical treatments – because of ripple effects that begin in our gut, new research suggests.
What we eat can affect the outcome of chemotherapy – and likely many other medical treatments – because of ripple effects that begin in our gut, new research suggests.
University of Virginia scientists found that diet can cause microbes in the gut to trigger changes in the host’s response to a chemotherapy drug. Common components of our daily diets (for example, amino acids) could either increase or decrease both the effectiveness and toxicity of the drugs used for cancer treatment, the researchers found.
The discovery opens an important new avenue of medical research and could have major implications for predicting the right dose and better controlling the side effects of chemotherapy, the researchers report. The finding also may help explain differences seen in patient responses to chemotherapy that have baffled doctors until now.
“The first time we observed that changing the microbe or adding a single amino acid to the diet could transform an innocuous dose of the drug into a highly toxic one, we couldn’t believe our eyes,” said Eyleen O’Rourke, PhD, of UVA’s College of Arts & Sciences, the School of Medicine’s Department of Cell Biology and the Robert M. Berne Cardiovascular Research Center. “Understanding, with molecular resolution, what was going on took sieving through hundreds of microbe and host genes. The answer was an astonishingly complex network of interactions between diet, microbe, drug and host.”
How Diet Affects Chemotherapy
Doctors have long appreciated the importance of nutrition on human health. But the new discovery highlights how what we eat affects not just us but the microorganisms within us.
The changes that diet triggers on the microorganisms can increase the toxicity of a chemotherapeutic drug up to 100-fold, the researchers found using the new lab model they created with roundworms. “The same dose of the drug that does nothing on the control diet kills the [roundworm] if a milligram of the amino acid serine is added to the diet,” said Wenfan Ke, a graduate student and lead author of a new scientific paper outlining the findings.
Further, different diet and microbe combinations change how the host responds to chemotherapy. “The data show that single dietary changes can shift the microbe’s metabolism and, consequently, change or even revert the host response to a drug,” the researchers report in their paper published in Nature Communications.
In short, this means that we eat not just for ourselves but for the more than 1,000 species of microorganisms that live inside each of us, and that how we feed these bugs has a profound effect on our health and the response to medical treatment. One day, doctors may give patients not just prescriptions but detailed dietary guidelines and personally formulated microbe cocktails to help them reach the best outcome.
Researchers have observed microbes and diet affecting treatment outcomes before. However, the new research stands out because it is the first time that the underlying molecular processes have been fully dissected.
A New Model
The researchers’ new model is an extremely simplified version of the complex microbiome – collection of microorganisms – found in people. Roundworms serve as the host, and non-pathogenic E. coli bacteria represent the microbes in the gut. In people, the relationships among diet, microorganisms and host is vastly more complex, and understanding this will be a major task for scientists going forward.
The research team noted that drug developers will need to take steps to account for the effect of diet and microbes during their lab work. For example, they will need to factor in whether diet could cause the microorganisms to produce substances, called metabolites, that could interfere or facilitate the effect of the drugs.
The researchers suggest that the complexity of the interactions among drug, host and microbiome is likely “astronomical.” Much more study is needed, but the resulting understanding, they say, will help doctors “realize the full therapeutic potential of the microbiota.”
“The potential of developing drugs that can improve treatment outcomes by modulating the microbes that live in our gut is enormous,” O’Rourke said. “However, the complexity of the interactions between diet, microbes, therapeutics and the host that we uncovered in this study is humbling. We will need lots of basic research, including sophisticated computer modeling, to reveal how to fully exploit the therapeutic potential of our microbes.”
The research team consisted of Ke, James A. Saba, Cong-Hui Yao, Michael A. Hilzendeger, Anna Drangowska-Way, Chintan Joshi, Vinod K. Mony, Shawna B. Benjamin, Sisi Zhang, Jason Locasale, Gary J. Patti, Nathan Lewis and O’Rourke.
NewsMakers
Study links coffee consumption to metabolic health and sex hormones
Despite having a similar body mass index (BMI), individuals with higher coffee consumption had lower total and visceral fat and greater skeletal muscle mass than those who consumed less coffee.
Coffee is one of the world’s most widely consumed beverages, and previous research has linked its consumption to a lower risk of conditions such as type 2 diabetes and cardiovascular disease. However, the biological mechanisms behind these benefits remain unclear. A new Finnish study links habitual coffee consumption to healthier body composition and metabolic markers, while revealing distinct associations with sex hormones in men and women.
The study, conducted at the University of Oulu, analysed data from 2,264 participants aged 46 in the Northern Finland Birth Cohort 1966. Researchers examined how habitual coffee consumption was associated with circulating metabolites, cardiometabolic risk markers and sex hormones.
Despite having a similar body mass index (BMI), individuals with higher coffee consumption had lower total and visceral fat and greater skeletal muscle mass than those who consumed less coffee.
In both men and women, higher coffee consumption was correlated with lower circulating levels of branched-chain amino acids, biomarkers that have previously been linked to insulin resistance and an increased risk of type 2 diabetes when chronically elevated.
The strongest sex-specific associations were observed in men. Higher coffee consumption was linked to a more favourable glucose–insulin profile, higher concentrations of total and bioavailable testosterone, and increased levels of sex hormone-binding globulin (SHBG). At the same time, free testosterone and the free androgen index were modestly lower. In women, hormonal associations were more limited and were primarily characterised by higher 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.
The results suggest that hormonal pathways may partly explain the relationship between coffee consumption and metabolic health. However, as this was an observational study, the findings demonstrate associations rather than cause-and-effect relationships.
The study is particularly relevant in Finland, one of the world’s highest coffee-consuming countries, where annual consumption averages around 11.8 kilograms per person.
The researchers say the findings provide a foundation for future studies aimed at determining whether coffee itself drives these biological changes and identifying the compounds responsible. These questions are currently being investigated in animal models, with the long-term goal of progressing to human intervention studies. Further research will be needed before the findings could inform dietary recommendations.
The study, Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland Birth Cohort 1966 study, has been published in the European Journal of Nutrition.
NewsMakers
Scheduling dental care during prenatal visits boosts oral health care during pregnancy
Scheduling a dental appointment during prenatal clinic visits—a simple, no-cost task that doesn’t require extra staff—increases the likelihood that patients later see a dentist during pregnancy.
Prenatal visits might include bloodwork, discussions of due dates and vitamins, and ultrasounds. What if these visits could also improve oral health care among pregnant patients?
New research shows that scheduling a dental appointment during prenatal clinic visits—a simple, no-cost task that doesn’t require extra staff—increases the likelihood that patients later see a dentist during pregnancy.
The study, published in the American Journal of Public Health, demonstrates the benefit of coordination among health providers and integrating oral health into prenatal care, especially for vulnerable patient populations.
Historically, dentists avoided treating women during pregnancy unless it was an emergency, or only provided care during the second trimester. This guidance changed once studies showed that routine and emergency dental care is safe during pregnancy—and current obstetric and dental guidelines stress that dental care can and should be provided during this critical period.
Moreover, pregnancy increases the risk of some oral health conditions, including gum inflammation and sometimes tooth decay, making routine dental care even more important during pregnancy. Some oral health issues may affect the fetus or even be transmissible to the child after birth.
Marginalized groups, including low-income individuals and those insured by Medicaid, are known to have higher rates of dental disease. Yet women enrolled in Medicaid are far less likely to see a dentist for a cleaning during pregnancy compared to women with private insurance.
“Many of those vulnerable to oral disease enter pregnancy with dental disease, and this may worsen during pregnancy,” said study author Stefanie Russell, associate professor at Rutgers School of Dental Medicine and an adjunct associate professor at NYU College of Dentistry, who led this research while at NYU.
One way to try and increase dental care among pregnant women is to reach them where they already are: their prenatal appointments. To bridge this gap, researchers and clinicians at NYU College of Dentistry teamed up with neighboring NYC Health + Hospitals/Bellevue, the oldest public hospital in the US, to create the New York University/Bellevue Prenatal Oral Health Program.
During weekly sessions at Bellevue’s prenatal clinic, pregnant patients receive a standardized screening to assess their oral health. Those with dental needs are referred to NYU College of Dentistry for follow-up care, educated about the importance and safety of dental care during pregnancy, and informed that Medicaid covers dental care in New York.
From 2018 to 2020, 420 prenatal patients with Medicaid coverage were referred to NYU Dentistry for follow-up dental care; the majority were Hispanic, and roughly half spoke Spanish as their first language. Referrals for dental care took two forms: immediately scheduled dental appointments made before the patient left the prenatal clinic or through a patient navigator. The patient navigator—a bilingual professional—educated patients regarding oral health, reminded patients of their upcoming dental appointments, and followed up after to identify any issues.
Nearly 44 percent of patients referred to NYU College of Dentistry followed through with a dental appointment. Both immediate appointment scheduling and the patient navigator increased the chances of a patient receiving dental care, but those who had appointments scheduled at their prenatal visit were 2.6 times more likely to see a dentist than those without appointments scheduled—even more likely than those who worked with the patient navigator.
“This suggests that immediately scheduled dental appointments can be an effective way to increase dental care utilization during pregnancy, without needing to hire extra staff,” said study author Shulamite Huang, assistant professor of epidemiology and health promotion at NYU College of Dentistry.
The authors conclude that integrating oral health screening in a prenatal clinic is feasible and increases engagement with dental care during pregnancy. They are continuing their research to measure whether this care improves oral health outcomes and to better understand how dental screening can be successfully integrated with prenatal care in other settings.
“A warm hand-off is key for addressing part of the barriers to dental care during pregnancy. Our team plans to further investigate and optimize interventions addressing both patient-, provider-, and healthcare system-level barriers to dental care during pregnancy,” said Huang.
Additional study authors include Richard Heyman and Mary Kang of NYU Dentistry; Belkys Saba, formerly of NYU Dentistry; Chloe Bird of the Tufts University School of Medicine; and Chengwu Yang of the Florida Atlantic University Schmidt College of Medicine.
NewsMakers
Why a UTI hurts — and why that might be a good thing
Australian researchers have discovered a previously overlooked group of bladder nerves that help detect urinary tract infections (UTIs) and trigger the body’s response to clear them, providing a potential new target for future bladder pain therapies.
Australian researchers have discovered a previously overlooked group of bladder nerves that help detect urinary tract infections (UTIs) and trigger the body’s response to clear them, providing a potential new target for future bladder pain therapies.
The study shows that bladder nerves located close to the lining of the bladder act as a frontline infection sensor, helping the body recognise UTIs and trigger responses that reduce the severity and spread of infection.
UTIs are among the most common bacterial infections worldwide, with more than 400 million cases reported every year. Nearly one in three women will experience UTIs before the age of 24, and many elderly people and those with bladder issues from spinal cord injuries can experience multiple UTIs in a single year.
Symptoms often include frequent urination, a sudden urge to urinate, pain during urination, and pelvic discomfort can be debilitating for some patients.
Flinders University’s Dr Luke Grundy says that while scientists have long understood how the bladder senses as it fills and triggers urination, the role of a specialised group of bladder nerves near the bladder lining has remained unclear.
“Most bladder nerves act like a fuel gauge, telling the brain when the bladder is filling up and needs emptying,” says Dr Grundy, Head of the NeuroUrology Research Group at Flinders University.
“The nerves we studied in this research are different. They sit close to the bladder lining and appear to act more like an early warning system, detecting infection and inflammation.
“They don’t just sense infection. They help coordinate the body’s response to it by triggering pain and urinary frequency, behaviours that appear to help clear bacteria from the bladder as part of the body’s defence system.”
Lead author and recently graduated PhD student Dr Cindy Tay says the discovery changes how these nerves are understood.
“These mucosal nerves have puzzled scientists for almost two decades because they stay quiet while the bladder fills and empties, which is the main job of the bladder,” says Dr Tay.
“What we’ve found is that they have a hidden job — acting as an early warning system that springs into action the moment infection takes hold.”
The research team developed a novel method to selectively study a specialised group of sensory nerves in the bladder lining of mice, revealing that while these nerves play little role in normal bladder function, they become highly responsive during a UTI and help detect and respond to infection.
“When the bladder is healthy, these nerves are relatively quiet, but during a urinary tract infection they become highly sensitive and respond to the presence of bacteria and inflammation,” says Dr Grundy.
“It may feel unpleasant, but urinating more frequently actually helps clear the infection by flushing out the harmful bacteria.”
The study also helps explain why people with conditions affecting nerve function may be more prone to recurrent or severe UTIs.
“If the nerves that detect infection aren’t working properly, the body may not respond as effectively,” says Dr Grundy.
Building on previous research, the new study reveals a deeper understanding of how UTIs affect bladder function and the nervous system, and could help develop new treatments that target these nerves to relieve UTI-related symptoms.
“Our findings provide new insight into how the bladder detects and responds to infection, helping explain the biological processes that drive the pain, urgency and discomfort commonly experienced during UTIs,” says Dr Grundy
Researchers say the next challenge is to develop therapies that ease the pain and urgency associated with UTIs while preserving the protective role these nerves play in fighting infection.
The paper, ‘Bladder mucosal afferents detect UTI and aid pathogen clearance,’ by Cindy Tay, Harman Sharma, Stewart Ramsay (University of Adelaide), Georgia Bourlotos, Sarah K Manning, Natalie E Stevens, Sophie J Miller, Geraint B Rogers, David J Lynn, Feargal J Ryan, Andrea M Harrington (University of Adelaide), Vladimir Zagorodnyuk, Steven L Taylor and Luke Grundy was published in Proceedings of the National Academy of Sciences (PNAS).
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