Researchers discover new bacterium that causes gut immunodeficiency

Cleveland Clinic researchers have discovered a new bacterium that weakens the immune system in the gut, potentially contributing to certain inflammatory and infectious gut diseases.

The team identified the bacterium, Tomasiella immunophila (T. immunophila), which plays a key role in breaking down a crucial immune component of the gut's multi-faceted protective immune barrier.

Identifying this bacterium is the first step to developing new treatments for a variety of inflammatory and infectious gut diseases. These conditions, including inflammatory bowel disease, Crohn's and ulcerative colitis, are associated with decreased levels of secretory immunoglobulin A (SIgA), an antibody that protects mucosal surfaces.

The study, published in Science, was led by Thaddeus Stappenbeck, M.D., Ph.D., chair of Cleveland Clinic's Department of Inflammation and Immunity, and Qiuhe Lu, Ph.D., research associate and the paper's first author.

"Our research represents a critical role of a specific component of the gut microbiome in human health and disease," said Dr. Stappenbeck. "By identifying this specific bacterium, we have not only enhanced our understanding of gut diseases but also opened a promising new avenue for treatment. Pinpointing the culprit behind the breakdown of the gut's protective adaptive immune barrier is a significant step toward developing much-needed therapies for conditions like inflammatory bowel disease, Crohn's and ulcerative colitis."

In the gut, SIgA binds continuously to microbes, preventing them from reaching and damaging the body's tissue. In previous research, the team discovered that intestinal bacteria could reduce SIgA levels, which can lead to increased risk of infection and excess inflammation.

In this new study, researchers found that T. immunophila'spresence in the gut increases susceptibility to pathogens and delays repair of the gut's protective barrier. T. immunophila'sname is an homage to a pioneer in immunology. SIgA was discovered by Dr. Thomas Tomasi, who published his findings in a foundational paper in Science in 1963.

"Drs. Stappenbeck and Lu's rigorous and elegant study provides a key insight and an exciting potential mechanism for why some people have low or absent levels of SIgA in their gut, yet retain normal levels of SIgA in their bloodstream," says Michael Silverman, M.D., Ph.D., a physician with the Division of Infectious Diseases at Children's Hospital of Philadelphia.

Dr. Silverman, whose expertise includes immune system development, provided input on the research findings. "This discovery is quite important, as SIgA in the intestine functions as a critical component of the barrier for the trillions of microbes that live in our intestines," Dr. Silverman said. "This study provides a new avenue to develop therapeutics to manipulate SIgA in the gut and improve health."

"We know that there are a substantial number of patients that have this defect in are at risk for infection and inflammation in the intestine," said Dr. Lu. "We surmised that a gut microbe that can degrade SIgA was the culprit. We believe that important therapeutic targets for a variety of inflammatory and infectious diseases in humans can be found through our work."

Journal Reference:

1. Qiuhe Lu, Thomas C. A. Hitch, Julie Y. Zhou, Mohammed Dwidar, Naseer Sangwan, Dylan Lawrence, Lila S. Nolan, Scott T. Espenschied, Kevin P. Newhall, Yi Han, Paul E. Karell, Vanessa Salazar, Megan T. Baldridge, Thomas Clavel, Thaddeus S. Stappenbeck. A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency. Science, 2024; 385 (6716) DOI: 10.1126/science.adk2536 

Courtesy:

Cleveland Clinic. "Researchers discover new bacterium that causes gut immunodeficiency." ScienceDaily. ScienceDaily, 26 September 2024. <www.sciencedaily.com/releases/2024/09/240926144904.htm>.

 

 

 

Getting the flu and then your shot may benefit immunity

 

In a new study funded by the National Institutes of Health, University of Georgia researchers found that natural immunity from previous flu infections has a significant impact on how well future influenza vaccinations work.

That may mean if you're one of the unlucky estimated 1 in 5 Americans who gets the flu each year, according to the NIH, there may be an unexpected upside to your illness.

It may help you battle future versions of the virus.

"Overall, the preexisting immunity you develop through natural infection helps to strengthen immune responses," said Ye Shen, study corresponding author and a professor in the UGA College of Public Health. "We didn't fully understand how preexisting immunity through natural infection with different influenza strains changes vaccine-elicited immune responses before this study. Now we have a better understanding of how preexisting immunity to influenza influences immune responses to different types of vaccines."

Flu shots aim to keep up with an evolving virus

Each flu season, your flu shot targets certain strains of the virus. So when scientists develop the influenza vaccine, they have to make educated guesses about which strains are most likely to be circulating ahead of time.

While plenty of research goes into developing the shot, it's never going to be right 100% of the time.

The flu virus's ability to constantly evolve and develop new and more virulent strains makes it difficult to fight.

"In some years, we don't have very good protection from the vaccine because of that mismatch," Shen said. "People have started to worry about whether the shot is actually protecting them from the flu because of that. With this study, though, we do see benefits of having preexisting immunity, and that's good to know."

Vaccination post-recovery can bolster immune system

The researchers tested vaccines made of various flu strains. They found when animals were infected with one strain of the flu, the animals had a heightened immune response when given a vaccine targeting that same strain.

But overall immunity also improved significantly when the animals were given a vaccine targeting a different flu strain, after being infected with the original strain of the virus.

With the body protecting itself against one strain with its natural immune response and the vaccine eliciting broader immune responses to a spectrum of flu strains, the body was better shielded.

Animals that were not initially infected with the virus but did get the vaccine were more likely to need a booster because they lacked natural immunity.

This research is part of a larger, seven-year NIH-funded study that aims to create universal influenza vaccines for vulnerable populations.

"Our future studies will further explore more clinically relevant outcomes including actual infections in humans. It may not be enough just to push your antibodies higher," Shen said. "Is that enough to protect you from mutations of different influenza strains? This is where individual-level heterogeneity becomes important, which remains an ongoing area of research in the field."

Published in the journal Vaccine, the study was co-authored by Yao Lu, who also conducted much of the data analysis, and Andreas Handel, from the UGA College of Public Health, and Ted Ross, of the UGA College of Veterinary Medicine. Additional co-authors include Yang Ge, James D. Allen, Tal Einav, Dennis I. Nkaleke and Fengwei Bai.

Journal Reference:

1. Yang Ge, Yao Lu, James D. Allen, Tal Einav, Dennis I. Nkaleke, Fengwei Bai, Andreas Handel, Ted M. Ross, Ye Shen. Pre-existing immunity to influenza aids ferrets in developing stronger and broader H3 vaccine-induced antibody responses. Vaccine, 2024; 42 (21): 126149 DOI: 10.1016/j.vaccine.2024.07.050 

Courtesy:

University of Georgia. "Getting the flu and then your shot may benefit immunity." ScienceDaily. ScienceDaily, 30 September 2024. <www.sciencedaily.com

/releases/2024/09/240930122824.htm>.