Archive for month: March, 2025

Exposure to antibiotics during a key developmental window in infancy can stunt the growth of insulin– producing cells in the pancreas and may boost risk of diabetes later in life, new research in mice suggests.

The study, published this month in the journal Science, also pinpoints specific microorganisms that may help those critical cells proliferate in early life.

The findings are the latest to shine a light on the importance of the human infant microbiome-the constellation of bacteria and fungi living on and in us during our first few years. The research could lead to new approaches for addressing a host of metabolic diseases.

“We hope our study provides more awareness for how important the infant microbiome actually is for shaping development,” said first author Jennifer Hill, assistant professor in molecular, cellular and developmental biology at CU’s BioFrontiers Institute. “This work also provides important new evidence that microbe-based approaches could someday be used to not only prevent but also reverse diabetes.”

Something in the environment

More than 2 million U.S. adults live with Type 1 diabetes, an incurable disease in which the pancreas fails to make insulin (the hormone that turns glucose into energy) and the blood fills with sugar.

The disease typically emerges in childhood, and genetics play a strong role. But scientists have found that, while identical twins share DNA that predisposes them to Type 1 diabetes, only one twin usually gets the disease.

“This tells you that there’s something about their environmental experiences that is changing their susceptibility,” said Hill.

For years, she has looked to microbes for answers.

Previous studies show that children who are breastfed or born vaginally, which can both promote a healthy infant microbiome, are less likely to develop Type 1 diabetes than others. Some research also shows that giving babies antibiotics early can inadvertently kill good bugs with bad and boost diabetes risk.

The lingering questions: What microbes are these infants missing out on?

“Our study identifies a critical window in early life when specific microbes are necessary to promote pancreatic cell development,” said Hill.

A key window of opportunity

She explained that human babies are born with a small amount of pancreatic “beta cells,” the only cells in the body that produce insulin.

But some time in a baby’s first year, a once-in-a-lifetime surge in beta cell growth occurs.

“If, for whatever reason, we don’t undergo this event of expansion and proliferation, that can be a cause of diabetes,” Hill said.

She conducted the current study as a postdoctoral researcher at the University of Utah with senior author June Round, a professor of pathology.

They found that when they gave broad-spectrum antibiotics to mice during a specific window (the human equivalent of about 7 to 12 months of life), the mice developed fewer insulin producing cells, higher blood sugar levels, lower insulin levels and generally worse metabolic function in adulthood.

“This, to me, was shocking and a bit scary,” said Round. “It showed how important the microbiota is during this very short early period of development.”

Lessons in baby poop

In other experiments, the scientists gave specific microbes to mice, and found that several they increased their production of beta cells and boosted insulin levels in the blood.

The most powerful was a fungus called Candida dubliniensis.

The team used fecal samples from The Environmental Determinants of Diabetes in the Young (TEDDY) study to make what Hill calls “poop slushies” and fed them to the mice.

When the researchers inoculated newborn mice with poop from healthy infants between 7 to 12 months in age, their beta cells began to grow. Poop from infants of other ages did not do the same.

Notably, Candida dublineinsis was abundant in human babies only during this time period.

“This suggests that humans also have a narrow window of colonization by these beta cell promoting microbes,” said Hill.

When male mice that were genetically predisposed to Type 1 diabetes were colonized with the fungus in infancy, they developed diabetes less than 15% of the time. Males that didn’t receive the fungus got diabetes 90% of the time.

Even more promising, when researchers gave the fungus to adult mice whose insulin-producing cells had been killed off, those cells regenerated.

Too early for treatments

Hill stresses that she is not “anti-antibiotics.”

But she does imagine a day when doctors could give microbe-based drugs or supplements alongside antibiotics to replace the metabolism-supporting bugs they inadvertently kill.

Poop slushies (fecal microbiota transplants) have already been used experimentally to try to improve metabolic profiles of people with Type 2 diabetes, which can also damage pancreatic beta cells.

But such approaches can come with real risk, since many microbes that are beneficial in childhood can cause harm in adults. Instead, she hopes that scientists can someday harness the specific mechanisms the microbes use to develop novel treatments for healing a damaged pancreas—reversing diabetes.

She recently helped establish a state-of-the-art “germ-free” facility for studying the infant microbiome at CU Boulder. There, animals can be bred and raised in sterile “bubbles” entirely without microbes, and by re-introducing them one by one scientists can learn they work.

“Historically we have interpreted germs as something we want to avoid, but we probably have way more beneficial microbes than pathogens,” she said. “By harnessing their power, we can do a lot to benefit human health.”

Reference:

Jennifer Hampton Hill et al. ,Neonatal fungi promote lifelong metabolic health through macrophage-dependent β cell development.Science387,eadn0953(2025).DOI:10.1126/science.adn0953

Researchers have found in a new research that malocclusion Impact Questionnaire is useful Tool for Assessing Malocclusion Impact on OHRQoL.The study highlights the effectiveness of the Malocclusion Impact Questionnaire (MIQ) in evaluating the impact of malocclusion on Oral Health-Related Quality of Life (OHRQoL) in orthodontics. The differences in OHRQoL between children with and without severe hypodontia (missing ≥5 teeth) were minimal. Delaying treatment until the patient expresses a subjective need may help prevent unnecessary treatments in children with hypodontia.

Steroid hormone levels in healthy adults are influenced by oral contraceptives and smoking, as well as other lifestyle choices and factors such as biological sex and age, according to new research that has just been published in leading international journal Science Advances.

The objective of the research was to expand knowledge and understanding of steroid hormone levels, including corticoids and sex hormones, in healthy women and men over a broad age range. This is the first study to analyse such a large number of hormones in nearly 1,000 healthy people, filling a major gap in the knowledge of molecules that are important for our day-to-day well-being.

The work was conducted by members of the Milieu Interieur consortium and led by Dr Darragh Duffy (Institut Pasteur) and Dr Molly Ingersoll (Institut Pasteur and Institut Cochin (Inserm U1016, CNRS, Université Paris Cité). Dr Jamie Sugrue, a Trinity College Dublin graduate, now a Marie Curie-funded postdoctoral researcher at the Institut Pasteur, is the co-first author. Dr Sugrue also worked with Trinity’s Professor Cliona O’Farrelly to secure a Research Ireland Ulysses grant, which kickstarted the ongoing collaboration between Trinity researchers and the Pasteur and Milieu Interieur consortium teams.

The team involved in this current study found that hormone levels vary according to an individual’s age and sex, but that they are also associated with many other factors, such as genetics and common behaviours.

Notably, many steroid hormone levels, beyond sex hormones, are influenced by oral contraceptive use in women, while in men, smoking was associated with altered levels of nearly every steroid hormone measured.

Additionally, measurement of hormones in the same donors 10 years after the original visit showed that decreases in specific androgens were associated with diverse diseases in aging men, implying that these hormones – which are associated with physical characteristics, and supporting strong bones and red blood cell production – play a role in disease development.

This finding – among others – gives the team numerous avenues to pursue in future research.

Dr Sugrue said: “Even in healthy people, immune responses can vary dramatically. As a first step towards understanding how hormones impact immunity, we worked to understand how hormones themselves vary among people. Our study provides a significant resource for the research community, and generates many new hypotheses for further research. Our next steps will focus on understanding how variation in hormone levels contribute to differences in the immune response between people.”

“My current project is specifically focused on variation in antiviral immune responses in healthy people, and in many ways is a continuation of work that I started during my PhD with Prof. Cliona O’Farrelly at Trinity, where we worked on how antiviral immune system variation can confer resistance to hepatitis C virus infection. By incorporating the hormone measures into my current analysis I hope to uncover exciting new insights.”

Cliona O’Farrelly, Professor of Comparative Immunology in Trinity’s School of Biochemistry and Immunology, added: “If the COVID pandemic taught us anything it was how different all our immune systems are, and being part of the Milieu Interieur collaboration is giving us Trinity researchers a wonderful opportunity to study the molecular and genetic mechanisms responsible for these differences at scale.”

Co-first author, Dr Léa G Deltourbe, Institut Pasteur & Institut Cochin, added: “This study brings much needed data to a subject that is receiving a lot of interest in the mainstream news and on social media platforms, providing a strong basis for investigating the role of steroid hormones in health and disease, including the impact of endocrine disruptors, the link between stress and cortisol, and the role of sex hormones on our well-being.”

As one example, understanding the potential effects of the contraceptive pill on physical and mental health should lead to a better quality of life for women choosing to use this form of medication.

Reference:

Léa G. Deltourbe et al. ,Steroid hormone levels vary with sex, aging, lifestyle, and genetics.Sci. Adv.11,eadu6094(2025).DOI:10.1126/sciadv.adu6094

Researchers have found in a new study published in Eye that gastroesophageal reflux disease (GERD) significantly increases the risk of primary acquired nasolacrimal duct obstruction (PANDO), especially among women and older adults. The findings show that patients who have GERD face more than twofold risk of PANDO compared to those who do not have GERD. The study was conducted by Yung-Yu Chu and fellow researchers.

Mothers experience major metabolic adaptations during pregnancy and lactation to support the development and growth of the new life. Although many metabolic changes have been studied, body temperature regulation and environmental temperature preference during and after pregnancy remain poorly understood. Researchers at Baylor College of Medicine and collaborating institutions show in the journal Molecular Metabolism that postpartum female mice develop new environmental temperature preferences and reveal brain changes mediating these changes.

“In both humans and mice, body temperature increases during early pregnancy, drops to normal temperature during late pregnancy and then goes up again during lactation,” said co-corresponding author Dr. Chunmei Wang, assistant professor of pediatrics at USDA/ARS Children’s Nutrition Research Center at Baylor.

In this study, Wang and her colleagues investigated what changes occurred in the brain that mediated the new temperature preference. “We worked with mice and found that female mice prefer a cooler environment starting from late pregnancy and persisting in long-term postpartum,” Wang said. “For more than four weeks post-weaning female mice had a lower body temperature and preferred cooler environments; they lost their typical preference for warm environments (30 °C/86 °F) but still avoided cold environments (15 °C/59 °F).”

To identify the biological underpinnings of these changes, the researchers studied the preoptic area (POA), a brain region important for sensing and regulating body temperature. “We discovered that the change in temperature preference in postpartum female mice was associated with a significant decrease in a particular group of neurons, estrogen receptor alpha (ERα)-expressing neurons in the preoptic area of the brain (ERαPOA neurons),” Wang said.

Supporting this finding, the researchers found that virgin females in which the estrogen receptor alpha had been deleted in ERαPOA neurons also preferred lower temperatures and avoided warmer locations, mimicking postpartum females.

Looking closely into the ERαPOA neurons, the researchers found that these neurons vary in their ability to sense warm or cold temperatures – one group of ERαPOA neurons can directly respond to warmth, while another group responds to cooler temperatures. “Interestingly, compared to female mice that had not been pregnant, ERαPOA neurons of postpartum females had reduced response to warmth and an enhanced response to cold,” Wang said.

Together, the results support that the ability of ERαPOA neurons to sense warmth and cold is regulated by reproductive experience and leads to changes in temperature preferences that alter the animal’s warmth-seeking behavior. Currently, the researchers are exploring the function of each group of ERαPOA neurons on the regulation body temperature and thermal preference.

Reference:

Nan Zhang, Meng Yu, Qianru Zhao, Bing Feng, Yue Deng, Jonathan C. Bean, Qingzhuo Liu, Benjamin P. Eappen, Yang He, Kristine M. Conde, Hailan Liu, Yongjie Yang, Longlong Tu, Mengjie Wang, Yongxiang Li, Na Yin, Hesong Liu, Junying Han, Darah Ave Threat, Nathan Xu, Taylor Smiley, Pingwen Xu, Lulu Chen, Tianshu Zeng, Yanlin He, Chunmei Wang, Altered thermal preference by preoptic estrogen receptor alpha neurons in postpartum females, Molecular Metabolism, https://doi.org/10.1016/j.molmet.2025.102108.