Medical Bulletin 18/ March/ 2024

Here are the top medical news for the day:

Can gut bacteria help shape newborn’s immune system?

Researchers from Weill Cornell Medicine have discovered that unique bacteria colonize the gut shortly after birth and make the neurotransmitter serotonin to educate gut immune cells that help in preventing allergic reactions to food and the bacteria themselves during early development.

The study published in the journal Science Immunologyon March 15, 2024 revealed that bacteria abundant in the guts of newborns produce serotonin, which promotes the development of immune cells called T-regulatory cells or Tregs. These cells suppress inappropriate immune responses to help prevent autoimmune diseases and dangerous allergic reactions to harmless food items or beneficial gut microbes.

"The gut is now known as the second human brain as it makes over 90 percent of the neurotransmitters in the human body. While neurotransmitters such as serotonin are best known for their roles in brain health, receptors for neurotransmitters are located throughout the human body," explained the study's senior author, Dr. Melody Zeng, an assistant professor of immunology in the Gale and Ira Drukier Institute for Children's Research and the Department of Pediatrics at Weill Cornell Medicine.

For the study, researchers analyzed neonatal mouse gut and observed that they had much higher levels of neurotransmitters, including serotonin, than the adult gut.

"So far, almost all studies of gut neurotransmitters were conducted in adult animals or human subjects, where a specific gut cell type called enterochromaffin cells produce neurotransmitters," said Dr. Zeng. "However, we discovered that this isn't the case in the newborn gut where most of the serotonin is made by bacteria that are more abundant in the neonatal gut."

The study results suggested that before the neonatal gut is mature enough to make its own neurotransmitters, unique gut bacteria may supply neurotransmitters that are needed for critical biological functions during early development.

"We found that gut bacteria in young mice not only directly produce serotonin but also decrease an enzyme called monoamine oxidase that normally breaks down serotonin, thus keeping gut serotonin levels high," said the study's lead author Dr. Katherine Sanidad, postdoctoral associate in pediatrics at Weill Cornell Medicine.

Reference:Katherine Z. Sanidad, Stephanie L. Rager, Hannah C. Carrow, Aparna Ananthanarayanan, Ryann Callaghan, Lucy R. Hart, Tingting Li, Purnima Ravisankar, Julia A. Brown, Mohammed Amir, Jenny C. Jin, Alexandria Rose Savage, Ryan Luo, Florencia MardorskyRowdo, M. Laura Martin, Randi B. Silver, Chun-Jun Guo, Jan Krumsiek, Naohiro Inohara, Melody Y. Zeng. Gut bacteria–derived serotonin promotes immune tolerance in early life. Science Immunology, 2024; 9 (93) DOI: 10.1126/sciimmunol.adj4775

Children with language disorder show abnormal brain structure, finds study

According to a study conducted by neuroscientists at the Georgetown University Medical Center, a part of the brain traditionally associated with movement is abnormal in children with developmental language impairments.

The study published in the journal Nature Human Behaviourfound that abnormalities occurred specifically in the anterior neostriatum within the basal ganglia, a structure found deep in thebrain.

To understand why language impairments occur, the researchers analyzed the results of 22 articles examining brain structures in people with the disorder, and then employed a computational method to identify common patterns of abnormalities across the studies. They determined that the anterior neostriatum was abnormal in 100% of the studies that examined the structure, with fewer abnormalities in all other parts of the brain.

The findings underscored the potential utility of drugs that are known to improve movement impairments due to basal ganglia dysfunction, such as those that act on dopamine receptors. Interventions that encourage compensation by intact brain structures may also be useful. Additionally, basal ganglia abnormalities could potentially serve as early biomarkers of an increased likelihood of developmental language problems. Such early warning signs could trigger further diagnostic procedures, potentially leading to early therapy.

“We hope that by identifying the neural bases of developmental language difficulties we may help increase awareness of a major, but also rather unrecognized, disorder. We caution, however, that further research is necessary to understand exactly how the anterior neostriatum might lead to the language difficulties.”said the study’s lead author Michael T. Ullman, PhD, professor of neuroscience and director of the Brain and Language Laboratory at Georgetown University Medical Center.

Reference:Michael T. Ullman, Gillian M. Clark, Mariel Y. Pullman, Jarrett T. Lovelett, Elizabeth I. Pierpont, Xiong Jiang & Peter E. Turkeltaub; The neuroanatomy of developmental language disorder: a systematic review and meta-analysis; Journal: Nature Human Behaviour; DOI: 10.1038/s41562-024-01843-6

DNA origami vaccines for precise cancer immunotherapy: Study

A team of scientistsfrom the Wyss Institute at Harvard University, Dana-Farber Cancer Institute (DFCI), Harvard Medical School (HMS), and Korea Institute of Science and Technology (KIST) created a DNA origami platform called DoriVac, whose core component is a self-assembling square block-shaped nanostructure.

The findings were published in the Journal Nature Nanotechnology.

Therapeutic cancer vaccines, a promising form of immunotherapy, target and eliminate cancer cells while preventing recurrence and spread. They contain tumor antigens, including neoantigens, stimulating the immune system. Adjuvant molecules activate antigen-presenting cells (APCs), which present antigens to T cells, triggering rapid tumor response and long-term immunity.

The DNA origami vaccine enables precise attachment of adjuvant molecules and tumor antigens on a square block. Spacing CpG adjuvant molecules 3.5 nanometers apart effectively stimulated APCs, generating cytotoxic T cells, Th-1 polarized T cells, and memory T cells. DoriVac vaccines also improved tumor control and mouse survival, particularly when paired with immune checkpoint inhibitors.

“DoriVac’s DNA origami vaccine technology merges different nanotechnological capabilities that we have developed over the years with an ever-deepening knowledge about cancer-suppressing immune processes. We envision that in the future, antigens identified in patients with different types of tumors could be quickly loaded onto prefabricated, adjuvant-containing DNA origami to enable highly effective personalized cancer vaccines that can be paired with FDA-approved checkpoint inhibitors in combination therapies,”said Wyss Faculty member William Shih, Ph.D., who led the Wyss Institute team together with first-author Yang (Claire) Zeng, M.D., Ph.D.

Zeng and colleagues created DoriVac vaccines with varying distances between CpG strands and attached antigens on a square block. They used a method to protect the structures from degradation in the body. The DoriVac vaccines enhanced antigen uptake by APCs, especially dendritic cells. A spacing of 3.5 nanometers between CpG strands yielded the most potent APC responses, surpassing control vaccines with free CpG molecules.

“The DoriVac platform is our first example of how our pursuit of what we call Molecular Robotics can lead to entirely new and powerful therapeutics. This technology opens an entirely new path for development of designer vaccines with properties tailored to meet specific clinical challenges. We hope to see its rapid translation into the clinic,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital.

Reference:Yang C. Zeng, Olivia J. Young, Christopher M. Wintersinger, Frances M. Anastassacos, James I. MacDonald, Giorgia Isinelli, Maxence O. Dellacherie, Miguel Sobral, Haiqing Bai, Amanda R. Graveline, Andyna Vernet, Melinda Sanchez, Kathleen Mulligan, Youngjin Choi, Thomas C. Ferrante, Derin B. Keskin, Geoffrey G. Fell, Donna Neuberg, Catherine J. Wu, David J. Mooney, Ick Chan Kwon, Ju Hee Ryu & William M. Shih; Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination; Journal: Nature Nanotechnology