Intestinal cells communicate with probiotic gut microbes for a healthy immune system
The human body is swarming with bacteria and other microbes that outnumber our own cells by more than ten to one. From the soles of our feet to the follicles on our head and every crevice in between, trillions of microbes form specialized ecosystems collectively known as our microbiota. Far from being mere freeloaders, many of our microbial ecosystems are comprised of essential residents – friendly bacteria called commensals. In the gut, these microbial allies help us to digest our food, synthesize vital nutrients such as vitamins, and keep pathogens at bay.
They also speak to us. By listening to the chemical chatter of our microbial lodgers, epithelial cells that line the inner surface of our gut can distinguish friend from foe.
Learning to decipher the chemical cacophony is critical to the development of a healthy immune system, and when the system breaks down, debilitating conditions like inflammatory bowel disease can take hold.
It turns out that our microbes are listening to us, just as much as we are listening to them. And according to a team of Finnish researchers, the dialogue between us and our microbes changes the way that both of us behave.
The research, reported this week in PLoS ONE, started with a dose of scientific serendipity. Minna Tiittanen and her colleagues at the Finnish Red Cross Blood Service were looking for a way of replicating the human gut in a test tube. This simulated gut, made from a layer of human gut epithelial cells bathed in a nutrient broth, could potentially be an indispensable tool for microbiota research.
Making a plastic well that mimics the environment of the intestine requires a bit of tinkering. You need to find the best ingredients for your nutrient broth, and the optimum growth conditions to keep your commensals happy. While tinkering with different growth conditions, the team made an intriguing observation: Lactobacillus casei bacteria thrived in wells that contained intestinal epithelial cells, compared with wells that contained nutrient broth alone. This was despite the nutrient broth – not the intestinal cells – being the presumed source of nutrients for the bacteria.
L. casei is a garden variety gut commensal that is commonly used as a health-promoting probiotic in yoghurts. It has also been shown to improve survival in mice fighting bacterial pathogens such as Salmonella. The intestinal cells had the same growth-promoting effect on a related strain of probiotic bacteria, L. rhamnosus.
Lactobacillus species are known to interact with the gut immune system, keeping over-zealous immune responses in check by switching on genes in a class of immune cells called T regulatory cells. Tiittanen and her colleagues wondered whether the gut cells could also be having an effect on the L. casei cells, given how avidly the bacteria grew when the intestinal cells were present. In particular, the researchers wanted to know whether the L. casei cells primed by the gut cells became more potent immune cell stimulators.
The answer appears to be yes. The researchers collected bacteria grown in the test-tube gut culture system and placed them with peripheral blood mononuclear cells – a type of immune cells known to respond to L. casei. They then measured the amount of the anti-inflammatory compound interleukin-10 (IL-10) produced by the immune mononuclear cells.
L. casei grown in the intestinal cell cultured triggered a greater release of IL-10 from the immune mononuclear cells than L. casei cells grown in conventional nutrient broth. Their residence with the intestinal cells had rendered the bacteria more powerful immune stimulators of IL-10. Other pro- and anti-inflammatory compounds did not respond in the same way, suggesting that the response is highly specific.
After five days, a higher number of immune mononuclear cells cultivated with the primed bacteria had become T regulatory cells, compared with the immune cells grown with un-primed bacteria. The primed bacteria were helping to drive differentiation of the immune cells into cells that help the immune system to keep auto-immune conditions and over-zealous immune reactions at bay.
The findings of this study confirm how important our gut microbes are to our health. And the researchers have also proven that culture systems matter when it comes to investigating the complex interactions occurring within our microbial ecosystems, and between those ecosystems and ourselves.
But the study also raises the question of whether we need to be looking at different ways of producing probiotic bacteria in the lab, especially if we are considering using them for therapeutic applications. Probiotics may look the same when grown in standard nutrient broth, but they might not be as fluent in gut-speak as they would be if they were raised listening to the babble of real intestinal cells.
Reference: Tiittanen M, Keto J, Haiko J, Mättö J, Partanen J & Lähteenmäki K (2013). Interaction with intestinal epithelial cells promotes an immunosuppressive phenotype in Lactobacillus casei. PLoS ONE DOI: 10.1371/journal.pone.0078420