In the News

Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:

IRP analysis reveals a significant rise in use of complementary health approaches, especially for pain management

An analysis conducted by the National Institutes of Health’s National Center for Complementary and Integrative Health (NCCIH) reveals a substantial increase in the overall use of complementary health approaches by American adults from 2002 to 2022. The study, published in the Journal of the American Medical Association, highlights a surge in the adoption of complementary health approaches for pain management over the same period.

Researchers utilized data from the 2002, 2012, and 2022 National Health Interview Survey (NHIS) to evaluate changes in the use of seven complementary health approaches, including yoga, meditation, massage therapy, chiropractic care, acupuncture, naturopathy, and guided imagery/progressive muscle relaxation.

Switching to vegan or ketogenic diet rapidly impacts immune system

Researchers at the National Institutes of Health observed rapid and distinct immune system changes in a small study of people who switched to a vegan or a ketogenic (also called keto) diet. Scientists closely monitored various biological responses of people sequentially eating vegan and keto diets for two weeks, in random order. They found that the vegan diet prompted responses linked to innate immunity — the body’s non-specific first line of defense against pathogens — while the keto diet prompted responses associated with adaptive immunity — pathogen-specific immunity built through exposures in daily life and vaccination. Metabolic changes and shifts in the participants’ microbiomes — communities of bacteria living in the gut — were also observed. More research is needed to determine if these changes are beneficial or detrimental and what effect they could have on nutritional interventions for diseases such as cancer or inflammatory conditions.

Scientific understanding of how different diets impact the human immune system and microbiome is limited. Therapeutic nutritional interventions — which involve changing the diet to improve health — are not well understood, and few studies have directly compared the effects of more than one diet. The keto diet is a low-carbohydrate diet that is generally high in fat. The vegan diet eliminates animal products and tends to be high in fiber and low in fat.

The study was conducted by researchers from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the Metabolic Clinical Research Unit in the NIH Clinical Center. The 20 participants were diverse with respect to ethnicity, race, gender, body mass index (BMI), and age. Each person ate as much as desired of one diet (vegan or keto) for two weeks, followed by as much as desired of the other diet for two weeks. People on the vegan diet, which contained about 10% fat and 75% carbohydrates, chose to consume fewer calories than those on the keto diet, which contained about 76% fat and 10% carbohydrates. Throughout the study period, blood, urine, and stool were collected for analysis. The effects of the diets were examined using a “multi-omics” approach that analyzed multiple data sets to assess the body’s biochemical, cellular, metabolic, and immune responses, as well as changes to the microbiome. Participants remained on site for the entire month-long study, allowing for careful control of the dietary interventions.

Researchers create safer form of Coxiella burnetii for scientific use

Scientists have unexpectedly discovered that the weakened form of the bacteria Coxiella burnetii (C. burnetii) not typically known to cause disease, naturally acquired an ability to do so. C. burnetii causes Q Fever in humans and its weakened forms are those used for scientific purposes. Subsequently, the scientists identified the genetic mutation responsible for the increased ability to cause disease (virulence) and created a form of the bacteria without the genetic flaw that could safely be used for research. The study, by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health and collaborators at Washington State University and Northern Arizona University, is published in Nature Communications.

C. burnetti naturally infects livestock, including goats, sheep and cattle. The bacterium causes Q Fever, a rare human disease with fewer than 1,000 cases annually reported in the United States. Individuals at highest risk for C. burnetii infection include farmers, veterinarians and animal researchers as infection is caused by breathing dust contaminated by infected animal products, such as feces, urine, milk, and birth products. Q Fever is characterized by mild-to-severe flu-like symptoms and can be treated with antibiotics. Those who develop severe disease may experience infection of the lungs (pneumonia) or liver (hepatitis). A small percentage of people (fewer than 5 out of 100) who are infected develop a more serious infection called chronic Q fever, which develops months or years following the initial infection. This condition requires months of antibiotic treatment and can result in death.

A dry fracture of a Vero cell exposing the contents of a vacuole where Coxiella burnetii are busy growing.

A dry fracture of a Vero cell exposing the contents of a vacuole where Coxiella burnetii are busy growing.

Cognitive behavioral therapy alters brain activity in children with anxiety

NIH researchers found widespread differences in the brains of children with anxiety disorders that improved after treatment

Researchers at the National Institutes of Health have found overactivation in many brain regions, including the frontal and parietal lobes and the amygdala, in unmedicated children with anxiety disorders. They also showed that treatment with cognitive behavioral therapy (CBT) led to improvements in clinical symptoms and brain functioning. The findings illuminate the brain mechanisms underlying the acute effects of CBT to treat one of the most common mental disorders. The study, published in the American Journal of Psychiatry, was led by researchers at NIH’s National Institute of Mental Health (NIMH). 

“The findings can help our understanding of how and for which children CBT works, a critical first step in personalizing anxiety care and improving clinical outcomes,” said senior author Melissa Brotman, Ph.D., Chief of the Neuroscience and Novel Therapeutics Unit in the NIMH Intramural Research Program.

Sixty-nine unmedicated children diagnosed with an anxiety disorder underwent 12 weeks of CBT following an established protocol. CBT, which involves changing dysfunctional thoughts and behaviors through gradual exposure to anxiety-provoking stimuli, is the current gold standard for treating anxiety disorders in children.

IRP-developed HIV antibodies protect animals in proof-of-concept study

Three different HIV antibodies each independently protected monkeys from acquiring simian-HIV (SHIV) in a placebo-controlled proof-of-concept study intended to inform development of a preventive HIV vaccine for people. The antibodies — a human broadly neutralizing antibody and two antibodies isolated from previously vaccinated monkeys — target the fusion peptide, a site on an HIV surface protein that helps the virus fuse with and enter cells. The study, published in Science Translational Medicine, was led by the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Antibodies that target the fusion peptide can neutralize diverse strains of HIV in vitro, that is, in a test tube or culture dish outside of a living organism. The NIAID VRC isolated a fusion peptide-directed human antibody, called VRC34.01, from a person living with HIV who donated blood samples for research. They also isolated two antibodies from rhesus macaques — a species of monkey with immune systems like humans’ — who previously had received a vaccine regimen designed to generate fusion peptide-directed antibodies. Demonstrating that these antibodies protect animals would validate the fusion peptide as a target for human vaccine design. SHIV challenge—administering an infective dose of SHIV — to rhesus macaques is a widely used animal model for assessing the performance of HIV antibodies and vaccines.

In this study, rhesus macaques in each of four groups received a single intravenous infusion of one type of antibody — a 2.5 or 10 mg/kg of bodyweight dose of VRC34.01, or one of the two vaccine-elicited rhesus macaque antibodies — and other monkeys received a placebo infusion. To determine the protective effect of the antibodies, each monkey was challenged five days after infusion with a strain of SHIV known to be sensitive to fusion peptide-directed antibodies.

Transmission electron micrograph of HIV-1 virus particles (red) budding and replicating from a segment of a chronically infected H9 cell (blue)

Transmission electron micrograph of HIV-1 virus particles (red) budding and replicating from a segment of a chronically infected H9 cell (blue).

IRP researchers create single-cell atlas of the placenta during term labor

An atlas revealing the activity of individual placental cells during childbirth offers insight on what happens at the maternal-fetal interface during term labor, according to a study supported by the National Institutes of Health (NIH). The atlas provides a single-cell analysis of the human placenta and its surrounding membranes and is the first to use this method to understand the communication that occurs between maternal and fetal cells during the process of labor. Studying these processes aids understanding of typical labor and delivery at term, as well as preterm labor and delivery, which occurs before 37 weeks of pregnancy and is a leading cause of infant death and long-term disability. The work, led by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), is published in the latest issue of Science Translational Medicine.

The study team created the placental atlas by using single-cell RNA sequencing (also called single-cell transcriptomics), which examines the activity and signaling patterns of individual cells. The atlas, which is based on samples from 42 term pregnancies, describes changes in gene expression patterns among the different cell types in the placenta and its surrounding membranes, which include both maternal and fetal-derived cells.

The researchers found that cells most affected by labor were in the chorioamniotic membranes, which surround the fetus and rupture as part of the labor and delivery process. They also found that fetal stromal and maternal decidual cells were particularly active in generating inflammatory signaling. These findings are consistent with previous research showing that inflammation (unrelated to infection) is important for sustaining labor.

Reduced drug use is a meaningful treatment outcome for people with stimulant use disorders

NIH-supported findings suggest the need to expand definitions of addiction treatment success beyond abstinence

Reducing stimulant use was associated with significant improvement in measures of health and recovery among people with stimulant use disorder, even if they did not achieve total abstinence. This finding is according to an analysis(link is external) of data from 13 randomized clinical trials of treatments for stimulant use disorders involving methamphetamine and cocaine. Historically, total abstinence has been the standard goal of treatment for substance use disorders, however, these findings support the growing recognition that a more nuanced perspective on measuring treatment success may be beneficial.

The study, published in Addiction, was led by scientists at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in collaboration with researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

Researchers found that transitioning from high use (five or more days a month) to lower use (one to four days a month) was associated with lower levels of drug craving, depression, and other drug-related challenges compared to no change in use. These results suggest that reduction in use of methamphetamine or cocaine, in addition to abstinence, is a meaningful surrogate or intermediate clinical outcome in medication development for stimulant addiction. Unlike other substance use disorders, such as opioid use disorder or alcohol use disorder, there are currently no U.S. Food and Drug Administration-approved pharmacological treatments for stimulant use disorders.

“These findings align with an evolving understanding in the field of addiction, affirming that abstinence should be neither the sole aim nor only valid outcome of treatment,” said NIDA Director Nora Volkow, M.D. “Embracing measures of success in addiction treatment beyond abstinence supports more individualized approaches to recovery, and may lead to the approval of a wider range of medications that can improve the lives of people with substance use disorders.”

IRP researchers create genetic atlas detailing early stages of zebrafish development

Researchers at the National Institutes of Health have published an atlas of zebrafish development, detailing the gene expression programs that are activated within nearly every cell type during the first five days of development, a period in which embryos mature from a single cell into distinct cell types. These diverse cells become tissues and organs that form juvenile fish capable of swimming and looking for food. The findings are published in Developmental Cell.

“Perhaps surprisingly, tiny zebrafish provide us with significant insight into human development and disease. Many of the gene expression programs that direct embryonic growth are similar across fish, people, and other animals,” said Christopher McBain, Ph.D., scientific director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which conducted the work. “Since zebrafish are visibly transparent, fertilize eggs externally, and are easy to study genetically, they represent a unique and effective way to model human disease.”

The process of embryonic development is orchestrated by instructions in DNA that direct different programs of gene expression within individual cells, which give different cell types their unique functional characteristics. To create the atlas, the study team used a method called single-cell RNA sequencing to identify gene expression programs over the course of five days, with samples taken every two to 12 hours. The resulting atlas follows nearly 490,000 cells continuously over 120 hours after fertilization, with an average of 8,621 transcripts and 1,745 genes detected per cell. The study team then sorted these data among known cell types and cell states during development.

BEST4+ cells are labelled red along the zebrafish gastrointestinal tract

BEST4+ cells are labelled red along the zebrafish gastrointestinal tract. These understudied cells are linked to gastrointestinal diseases and cancer in people.

W. Kimryn Rathmell, M.D., Ph.D., begins work as 17th director of the National Cancer Institute

W. Kimryn Rathmell, M.D., Ph.D., began work today as the 17th director of the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). A renowned kidney cancer expert and influential leader in cancer research and patient care, Dr. Rathmell was selected by President Biden to succeed Monica M. Bertagnolli, M.D., who left NCI to become the NIH director on November 9.

“I want to officially welcome Dr. Rathmell to the National Cancer Institute on her first day as director,” said Department of Health and Human Services Secretary Xavier Becerra. “Dr. Rathmell begins her new role at an important time. The President and First Lady reignited the Biden Cancer Moonshot℠ to dramatically accelerate progress in the fight against cancer—and NCI is helping to lead the charge. Dr. Rathmell brings decades of experience helping to advance research and drive innovation to improve care for patients. She joins an extraordinary team already doing great work to prevent, detect, and treat cancer to make sure Americans are living longer, healthier lives. I look forward to working closely with Dr. Rathmell in the months and years ahead to help end cancer as we know it.”

“I am thrilled to welcome Dr. Rathmell to NIH, and I know she is the right leader at the right time for NCI,” said Dr. Bertagnolli. “She is a fantastic combination of researcher and clinician who deeply understands the process of translating lab research into effective cancer treatments. NCI is in great hands to actualize the brighter future we all want for people with cancer.”

Dr. W. Kimryn Rathmell

W. Kimryn Rathmell, M.D., Ph.D.

IRP research identifies opportunities to improve future HIV vaccine candidates

Study suggests greater CD8+ T-cell activity may increase HIV immunity

An effective HIV vaccine may need to prompt strong responses from immune cells called CD8+ T cells to protect people from acquiring HIV, according to a new study from researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and colleagues. The study findings, appearing in Science, draw comparisons between the immune system activity of past HIV vaccine study participants and people with HIV who naturally keep the virus from replicating even in the absence of antiretroviral therapy (ART). The latter individuals are often called “long-term non-progressors” or “elite controllers” (LTNPs/ECs).

When HIV enters the body, the virus begins to damage the immune system by inserting itself into CD4+ T cells, which are white blood cells that help coordinate the immune response to pathogens. In most people, HIV continues to replicate and damage more and more CD4+ T cells unless controlled by ART. Among LTNPs/ECs, the immune system appears to promptly recognize CD4+ cells with HIV and activate other immune cells called CD8+ T cells. CD8+ T cells destroy CD4+ cells with HIV, enabling the suppression of HIV in a person’s blood.

The aim of an effective HIV vaccine is to provide durable protective immunity to HIV, or if initial defenses are bypassed, to help control HIV in the body long term, as happens with LTNPs/ECs. Although several preventive HIV vaccine candidates have been designed to stimulate CD8+ T-cell activity, they did not prevent HIV acquisition or control viral replication in clinical trials. Understanding and addressing this lack of effect is a scientific priority of HIV vaccine research.

Scientists in the HIV-Specific Immunity Section of NIAID’s Laboratory of Immunoregulation and colleagues designed their study to better understand which CD8+ T-cell functions were lacking in previous HIV vaccine recipients. They compared laboratory samples from previous HIV vaccine study participants with samples from LTNPs/ECs. They found that both HIV vaccine recipients and LTNPs/ECs generated large numbers of CD8+ T cells that recognized HIV. However, unlike the CD8+ T cells of LTNPs/ECs, HIV vaccine recipients’ CD8+ T cells failed to deliver the proteins necessary to destroy HIV-infected CD4+ T cells with HIV.

Layout featuring colorized 3D prints of HIV virus particles (pink with teal surface proteins) and a background image that is a colorized transmission electron micrograph of HIV virus particles (pink) budding and replicating from an H9 T cell (purple)

Layout featuring colorized 3D prints of HIV virus particles (pink with teal surface proteins) and a background image that is a colorized transmission electron micrograph of HIV virus particles (pink) budding and replicating from an H9 T cell (purple). Micrograph captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Note: not to scale.

Continue Exploring the IRP

This page was last updated on Wednesday, May 11, 2022