Over the years, I’ve talked about Bacteriodes fragilis (B. fragilis) several times. It is one of those bacterial species that has two faces: some strains are beyond good for us – and some not. The non-toxic B. fragilis (NTBF) makes up about 1-2% of our fecal bacteria, and colonization begins at birth. Our bodies are primed to welcome the species: the immune system of the gut, IgA, helps it colonize. In a post from 2019, I talked about the fact that NTBF inhibits inflammation in various bodily organs, including the digestive tract, brain, and lungs. The bacteria secrete a molecule, a polysaccharide, called PSA, which boosts levels of regulatory cytokines, modulating inflammation
Bearing that information in mind, I was just amazed over the weekend reading about research just published out of Harvard University looking at how the gut microbiome works to protect us from viral infections.[i] Timely findings, to say the least. Remember that most germs enter through our nose and mouth. At least 70% of our immune system is, therefore, in our guts: it is our first line of defense against invaders. It turns out that specific species of gut bacteria cause immune cells to release a virus-repelling chemical called interferons. These scientists have actually isolated the molecule that stimulates the protective immune cascade, which could someday be made into antiviral medicines for us. Wouldn’t it be remarkable if the cure for the common cold ended up already being inside us?!
To explain: immune cells in the walls of the colon release interferons when stimulated to do so by a molecule that exists on the membrane of – you guessed it! – commensal bacteria like B. fragilis and select other Bacteroides. By activating an immune pathway called TLR4-TRIF signaling pathway, B. fragilis induces gut immune cells to release interferon beta, which both stimulates virus-infected cells to self-destruct and stimulates other kinds of immune cells to also attack the virus. That is, the molecule on the membrane of B. fragilis communicates with the immune cells, telling them to release the anti-viral interferon.
In further proof-of-concept testing, the scientists treated one group of mice with antibiotics, depleting their bacterial microbiomes, and then exposed them – as well as non-treated control mice – to a virus (vesicular stomatitis virus). The antibiotic-treated mice were not only more likely to develop active infections but those infections were also far more severe. The researchers then gave mice with depleted microbiomes the B. fragilis-derived signaling molecule in their water. When exposed to the virus a few days later, these mice had significantly milder infections and survived at the same rate as mice with intact microbiomes. Holy smokes.
Says one of the senior researchers, “Given the critical role that interferons play in disease and health, our identification of a bacterial molecule that can induce interferon protective signaling points to a promising new approach to develop a therapeutic compound that could boost antiviral immunity to reduce the risk for viral infections…” [ii]
Of course these experiments were conducted in animals, and the results have yet to be replicated in humans. Still, this is some seriously remarkable research that may have far reaching implications in the future. I’ve written on this blog about how, for example, a depleted microbiome is now associated with severe COVID infection. (See here and here.) I can finally really imagine a time in the future when these completely natural “2nd generation probiotics” are used to ameliorate or prevent so many illnesses that we cannot yet treat.
[i] Stefen, KL, Kim, MV, Iwasaki, A, Kasper, D. Commensal microbiota modulation of natural resistance to virus infection. Cell. 2020;183(5). DOI:https://doi.org/10.1016/j.cell.2020.10.047