The bacteria residing in our intestines help us digest our food, support our immune systems, and even contribute to the manufacture of certain vitamins. Yet the difficulty of reproducing their growth conditions in a lab means scientists have not been able to isolate, culture, and study most bacterial species. However, with the latest advances in medical technologies, scientists have begun to learn a great deal about these beneficial flora. Now, a new study may explain why patients with a rare hereditary disease known as common variable immune deficiency (CVID) suffer from recurrent bacterial infections. Leaky intestines may be crippling bacteria-fighting immune cells, Swiss researchers believe.

Gut Bacteria and CVID

Ten times as many microbial cells, compared to human cells, exist in your body. In fact, your intestine harbors nearly 100 trillion bacteria. In the past, scientists theorized that infants are born with sterile guts and only became colonized with microbiota within the first few days of life, but now it is known that infants begin acquiring intestinal flora when they ingest amniotic fluid in the womb. Additionally, while passing through the birth canal, an infant swallows bacteria from its mother. This initial colonization determines a lot of what follows in an infant’s life because these earliest bacteria influence the genetic expression of surrounding cells within the digestive tract and generally regulate the environment by creating one that is most favorable to themselves and less favorable to any other bacteria introduced later. The earliest settlers make the rules, so to speak.

Now, the activities of these gut bacteria have been linked to CVID, a disorder that impairs the immune system and expresses itself, in part, by lowering the levels of several of the proteins (antibodies) that help you fight infections. Patients with CVID have an increased risk of digestive disorders, blood disorders, and even cancer, plus they are open to recurrent infections in their ears, sinuses, and respiratory system. Despite these problems with immunity, CVID patients rarely contract viral infections. Why?

New data from Dr. Matthieu Perreau, Division of Immunology and Allergy, Department of Medicine, Lausanne University, and his colleagues show that bacteria-fighting T-cells in the blood of CVID patients showed signs of exhaustion, yet virus-fighting T-cells remained unscathed. Exploring further, they discovered T-cell exhaustion (evident by an inhibitory protein called PD-1) was associated with increased gut bacteria in the bloodstream. As a result, bacteria-specific T-cells may be repetitively stimulated.

However, the researchers believe tired T-cells within CVID patients could be rejuvenated by blocking PD-1. In patients who received infusions of antibodies (or IVIG therapy), PD-1 expression on T-cells waned along with the levels of bacteria in the blood. According to the researchers, then, the data suggest that immunotherapy strategies already in use in cancer patients would beneficially protect CVID patients against recurrent bacterial infection.

Source: Perreau M. et al. J. Exp. Med. 2014.