The researchers found that mouse pups that nursed from lactating mice whose breast milk lacked a key complement protein had different gut microbe populations than pups that nursed on standard mouse breast milk, making them highly vulnerable to Citrobacter rodentium, a bacterium that infects the guts of mice. Citrobacter rodentium is similar to certain types of diarrhea-causing E. coli that can infect humans but not mice.

The researchers’ experiments suggest that mouse breast milk’s complement components boost mouse infant health by directly eliminating some types of gut-dwelling bacteria. This reshaping of the gut microbiota leaves the infant mice far less susceptible to Citrobacter rodentium infection, thus protecting the young from certain infectious threats. The reshaping activity is not dependent on antibodies, in contrast to the way complement components are thought to typically work.

The researchers also confirmed in separate in vitro analyses that human breast milk contains these complement components, which demonstrated similar activity in targeting specific bacteria.

Taken together, these findings shed light on the mechanisms of how breast milk functions to provide protection from certain bacterial infections.

The study was published online January 18 in the journal Cell.

“These findings reveal a critical role for breast milk complement proteins in shaping offspring’s gut microbe compositions and protecting against bacterial infection in the gut in early life,” says study senior author Fengyi Wan, PhD, a professor in the Bloomberg School’s Department of Biochemistry and Molecular Biology. “This represents an important expansion of our understanding of breast milk’s protective mechanisms.”

The study’s first author is Dongqing Xu, PhD, an assistant scientist in Wan’s research group.

Breastfeeding has many known and suspected benefits. It provides excellent nutrition to infants and appears to protect against some short-term or long-term illnesses. Breast milk is also known to help protect against common infections by sharing antibodies and white blood cells from the mother.

Breast milk also contains complement proteins that can work with, or “complement,” antibodies in attacking bacteria. While complement proteins that circulate in the blood have been the focus of much research, complement proteins in breast milk have been far less studied, and until now their role has been unclear.

In the new study, Wan and his team used engineered mice that lacked critical complement genes. They found that milk from female mice of this type left several-weeks-old mouse pups — even those with normal complement genes — highly susceptible to colitis, often lethal, from Citrobacter rodentium infections. By contrast, pups feeding on normal, complement-containing milk showed only minor and transient signs of gut infection.

The team discovered that this protective effect of breast milk complement proteins depends on their capacity in shaping infant gut microbiota. The complement proteins kill certain gut bacterial species, and this culling of microbes creates an overall gut environment in which harmful inflammation is much less likely in the presence of Citrobacter rodentium.

“Gut microbiota is of great importance to health,” says Wan. “Breast milk complement proteins contribute crucially to the establishment of a ‘protective’ gut microbiota during the early stages of development, promoting infant health and defending against pathogens.”

The study also appears to mark an advance in basic immunology. Complement proteins in blood, although known to be capable of causing direct damage to bacterial cells, have been thought to typically work in partnership with antibodies in a specific immune response. However, Wan and his team showed that this breast milk complement activity against bacteria does not require antibodies and is a nonspecific immune response.

“This opens the door to a lot of new investigations, for example, elucidating the specific complement biology in breast milk and comparing that to complement biology in the blood, and assessing the role of complement beyond the antibody-dependent specific immune system,” Wan says.

Support for the research was provided by the National Institutes of Health (GM111682, AI137719, CA244350); the U.S. Department of Defense (W81XWH-19-1-0479); the American Association of Immunologists; and the American Heart Association (19PRE34380234).

An analysis of seawater collected around Santa Cruz Island, a human-populated island, with nearby Galápagos penguin colonies revealed plastic particles. Using models that focused on the Galápagos penguin diet (barracuda, sardine, herring, salema, and anchovy), and on penguin scat, researchers intuited a unique Galapagos penguin food web model using Ecopath and Ecosim (EwE) ecosystem modeling with the Ecotracer approach to track the bioaccumulation potential of microplastics in the penguins’ foodweb. They also applied a wider model for Bolivar Channel Ecosystem (between Fernandina and Isabela islands) and part of the penguin’s habitats, located at the western regions of the Galápagos Islands.

The model predictions showed a rapid increase in microplastic accumulation and contamination across the penguins’ prey organisms resulting in Galápagos penguin showing the highest level of microplastics per biomass, followed by barracuda, anchovy, sardine, herring, and salema and predatory zooplankton.

“The model predictions highlight the accumulation behavior and residence time of microplastics in the gut,” said Karly McMullen, first author and a former MSc student at the Institute for the Oceans and Fisheries at the University of British Columbia. “With microplastics emerging as a prominent ocean pollutant, entering the environment every day, there is a growing concern for marine fauna and coastal wildlife, particularly if this anthropogenic threat is reaching even the most remote and protected areas such as the Galápagos Archipelago.”

Senior autho, honorary research associate, and Principal Investigator of the Ocean Pollution Research Unit at Institute for the Oceans and Fisheries at the University of British Columbia, Dr. Juan Jose Alava, agreed. “The goal of this food web bioaccumulation modeling work was to provide science and data to support risk management of hazardous plastic waste, reduce microplastic emissions in the oceans and marine remote UNESCO Heritage sites such as the Galapagos Islands, and inform local and international marine policy to conserve endangered, endemic seabird species of Galapagos Marine Reserve.”

“It is imperative that we prioritizing efforts to reduce the input of microplastics into vulnerable ecosystems and food webs, particularly such as that of the endangered Galapagos penguin.”

The new system collects dirty water with a syringe and injects it into a hydrogel filter that weeds out nearly all tiny particles. This device, the researchers say, offers significant advantages in cost, simplicity, effectiveness and sustainability compared existing commercial options, giving users the ability to easily decontaminate water from nearby streams and rivers and make it drinkable.

“The pressing concern of particle-polluted water, particularly in remote and underdeveloped regions where people frequently rely on contaminated water sources for consumption, demands immediate attention and recognition,” said Guihua Yu, a professor of materials science at the Cockrell School of Engineer’s Walker Department of Mechanical Engineering and Texas Materials Institute. “Our system, with its high efficiency in removing diverse types of particles, offers an attractive yet practical solution in improving freshwater availability.”

The research was published recently in Nature Sustainability.

Today’s options for portable water filtration of tiny particles mostly consist of filter paper and microporous membranes. According to the research, these devices filter out roughly 40% and 80% of particles larger than 10 nanometers, respectively. This new system catches close to 100% of these particles.

And it is made of low-cost, sustainable, readily available materials. The main innovation is an intertwined web of nanocellulose fibers that catches particles while the newly cleaned water passes through.

All the user has to do is take the syringe to the nearest water source, pull out the water and inject it through the filter. The system takes care of the rest, spitting out clean, drinkable water.

The filter system has been tested with several types of water sources, including muddy water, river water and water contaminated with microplastics. The hydrogel films are biodegradable and can be used up to 30 times before they need to be replaced.

The research team has tested the technology using syringes as large as 1.5 liters, about 40% of an individual’s daily drinking water needs. And they plan to continue developing the technology to use it at larger scales to tackle global drinking water needs.

The researchers were motivated by one of the United Nations’ Sustainable Development Goals to improve drinking water standards and sanitation worldwide. Meeting this goal, according to the U.N., will require a 6X increase in drinking water availability by 2030.

“The reality is, a large percentage of the world’s population lacks access to safe drinking water, even in places where fresh water sources are available,” said Chuxin Lei, lead author and a graduate student working in Yu’s lab, said. “There is an urgent need for simple, universal, and efficient materials and devices for purifying particle-contaminated water, which should be able to help people around the world obtain clean water.”

Team members on the project also include collaborators from Northeast Forestry University, Shanghai Tech University and Tsinghua University in China.

GLP1 agonists like Ozempic reduce blood sugar levels and are mainly used to treat type 2 diabetes. However, as the drug also reduces appetite, it is now increasingly used to treat obesity and has become a popular weight-loss drug.

Reduced risk of liver damage

Results from early clinical trials also suggest that GLP1 agonists may reduce the risk of liver damage. Therefore, researchers at Karolinska Institutet included all people in Sweden with chronic liver disease and type 2 diabetes in a register-based study. They then compared the risk of severe liver damage in those who were treated with GLP1 agonists and those who were not. The results show that those who took the drug for a long period of time had a lower risk of later developing more severe forms of liver disease such as cirrhosis and liver cancer.

According to the researchers, this suggests that GLP1 agonists could be an effective treatment to avoid severe liver disease in people with concurrent type 2 diabetes.

“Fatty liver disease is estimated to affect up to one in five people in Sweden, many of whom have type 2 diabetes, and about one in twenty develop severe liver disease,” says first author Axel Wester, assistant professor at the Department of Medicine, Huddinge, Karolinska Institutet. “Our findings are interesting because there are currently no approved drugs to reduce this risk.”

Many of the people in the study stopped taking GLP1 agonists, resulting in a lack of protective effect. However, those who continued taking their medication over a ten-year period were half as likely to develop severe liver disease.

Need to be confirmed

“The results need to be confirmed in clinical trials, but it will take many years for these studies to be completed,” says Axel Wester. “Therefore, we use existing registry data to try to say something about the effect of the drugs before that.”

A limitation of the method is that it is not possible to control for factors for which there is no data, such as blood tests to describe the severity of liver disease in more detail. However, the researchers have recently built a new database called HERALD where they have access to blood samples from patients in Region Stockholm.

“As a next step, we will investigate the effect of GLP1 agonists in this database,” says the study’s last author Hannes Hagström, consultant in hepatology at the Karolinska University Hospital and adjunct professor at the Department of Medicine, Huddinge, Karolinska Institutet. “If we get similar results, it would further strengthen the hypothesis that GLP1 agonists can be used to reduce the risk of severe liver disease.”

The research was mainly funded by Region Stockholm (CIMED), the Swedish Research Council and the Swedish Cancer Society. Hannes Hagström’s research group has received funding from Astra Zeneca, EchoSens, Gilead, Intercept, MSD, Novo Nordisk and Pfizer, although no industry-supported funding was obtained for this specific study.

The resulting atlas reveals a slew of previously unknown cellular and molecular interactions that drive ovulation, which is crucial for female fertility. The findings could prove pivotal for developing therapeutic treatments for infertility.

The research, published Jan. 22 in Proceedings of the National Academy of Sciences, was led by Iwijn De Vlaminck, associate professor of biomedical engineering in Cornell Engineering, and Yi Ren, assistant professor of animal science in the College of Agriculture and Life Sciences. The paper’s lead author is Madhav Mantri, Ph.D. ’23, now a postdoctoral researcher at Stanford University.

De Vlaminck previously used the imaging method, high-resolution spatiotemporal transcriptomics, to survey the entire spectrum of RNA in mouse tissues, which showed the role of elusive RNA in skeletal muscle regeneration and viral myocarditis. Transcriptomics essentially converts RNA into DNA copies, which are tagged with barcodes that capture their spatial location — data that can then be sequenced into an image.

In 2022, De Vlaminck gave a presentation on the myocarditis findings at the 2nd Intercampus Immunology Symposium, which Ren attended. She was intrigued by De Vlaminck’s approach and wondered if it could be applied to one of her chief interests: unraveling the cellular and molecular mechanisms that regulate ovulation.

Ovulation requires accurate coordination between female germ cells, called oocytes, and their release via the rupture of ovarian follicles, which provide the environment for oocytes to grow and mature. In mice, this rupture occurs every four to five days; in women, it’s approximately every four weeks. Oocytes expire quickly once they depart the ovary, so the timing of their release is critical.

“Ovarian follicles are like launching pads, and the ovary is like the ground control. Together they prepare the eggs for fertilization at the right time and right location,” Ren said. “All the different cell types in the ovary must work together through an amazingly complex and dynamic ‘social network’ that involves intricated communication between all cells. That’s the power of Iwijn’s technology. It combines high resolution in both time and space. So those two really capture the essence of ovulation.”

In the years since De Vlaminck’s myocarditis study, the spatial resolution of transcriptomics has significantly improved, from 100 micrometers to 10 microns per pixel — a tenfold enhancement that has resulted in near single-cell resolution. The flip side to obtaining so much data, however, is that parsing it all is daunting.

“We had about 10 images and we spent a good 10 months making sense of them,” De Vlaminck said.

For each image, the researchers sequenced hundreds of millions of DNA molecules, then translated them into a matrix of gene expression. Every pixel contained the expression level of all 22,000 protein-coding genes in the mouse genome. Multiply that by approximately 100,000 pixels. And that was only the beginning.

“You have to turn that data into biological findings, look at temporal patterns, fish out specialized cell states and so on,” De Vlaminck said. “It’s not just like a normal microscopy image where you have the image, and that’s it, you see what you see.”

Among the findings, the atlas reveals that roughly one hour before an egg is released, the follicles undergo an additional layer of selection to determine which ones will ovulate. This acute process had never been identified before, and when it goes awry, it may lead to reduced ovulation rates and could hinder fertility. The researchers were also able to detect early differentiation markers that decide the different paths cells may take in the ovary. In effect, the atlas captures dynamic cellular and molecular control programs in both the very early and very late stages of ovulation.

“This type of atlas provides so much more detail about where and when all the molecular changes happen in the ovary, details that were difficult to capture using other methodologies,” De Vlaminck said. “So that may inspire new interventions that target specific molecules we identify, for example, specific genes that are important for fertility management.”

Now De Vlaminck and Ren, who are both faculty with the Cornell Reproductive Sciences Center, plan to extend their collaboration into exploring fertility and ovulation problems associated with obesity and reproductive aging.

In the U.S. alone, more than 10% of infertility cases are caused by ovulation failure, the researchers noted, a problem that is exacerbated by increasing obesity, and maternal age.

“There is a growing interest at Cornell in these types of problems, where we can use cutting-edge engineering principles for reproductive medicine — an area where those cutting-edge tools are not used as much, or as early, as in some other fields, like cancer biology, for instance,” De Vlaminck said.

Co-authors include doctoral student Hanxue Hannah Zhang and Emmanuel Spanos ’24.

The research was supported by the Cornell Center of Vertebrate Genomics and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.