Instead of injections or pills, why not engineer bacteria to secrete therapeutic molecules from within our gut? A new study is demonstrating this futuristic idea, showing how a genetically modified probiotic can produce an experimental anti-inflammatory molecule and effectively treat rheumatoid arthritis in rats.
"People don't like to have injections for the rest of their lives," said co-corresponding author Christine Beeton, from the Baylor College of Medicine. "In the current work, we explored the possibility of using the probiotic bacteria Lactobacillus reuteri as a novel oral drug delivery platform to treat rheumatoid arthritis in an animal model."
The new research focused on engineering a strain of Lactobacillus reuteri bacteria, which has previously been established to be a safe probiotic in humans. Plus, according to Beeton, the bacteria is not known to colonize the gut, so its effects on patients will only ever be transitory.
"Another reason we chose L. reuteri is that these bacteria do not remain in the gut permanently," added Beeton. "They are removed as the gut regularly renews its inner surface layer to which the bacteria attach. This opens the possibility for regulating treatment administration."
The researchers modified the bacteria to secrete a peptide called ShK-235, which is an analog of a peptide extracted from the Caribbean sea anemone. Over the last decade this molecule has been closely studied for its anti-inflammatory properties. In particular, it has been found to block the activation of certain immune cells implicated in diseases such as psoriasis, rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis.
In its synthetic therapeutic form the drug has been named Dalazatide. Ongoing late-stage clinical trials are proving promising for the drug to safely and effectively treat psoriasis and lupus in humans but it has yet to be authorized for clinical uses.
In this study the researchers tested their engineered peptide-secreting bacteria on animal models of rheumatoid arthritis. These preliminary experiments found daily doses of the probiotic reduced signs of disease and joint inflammation in rats.
The experiments also revealed the probiotic successfully released consistent and therapeutic levels of ShK-235 into the animals' bloodstream. So it is plausible that daily probiotic pills could become an effective way of delivering certain medicines that previously could only be administered through injection or intravenous infusion.
"These bacteria could be stored in capsules that can be kept on the kitchen counter," Beeton added. "A patient could take the capsules when on vacation without the need of refrigeration or carrying needles and continue treatment without the inconvenience of daily injections."
While this study is certainly an impressively advanced investigation into the idea of genetically modifying bacteria for therapeutic uses, it isn't the first time this futuristic concept has been explored. Last year researchers presented a novel strain of the human probiotic E.coli Nissle that had been modified to synthesize a Parkinson's disease drug called L-DOPA. Another earlier study engineered the same bacteria to act as a sponge to mop up excess ammonia in a human body.
Of course, don't expect to see genetically modified therapeutic probiotic bacteria being prescribed by doctors anytime soon. There is a long road of research ahead before these kinds of deeply experimental therapies can be safely and effectively deployed in humans.
Nevertheless, the idea is fascinating. After all, we know the bacteria living in our gut are constantly secreting metabolites that influence our health and well-being, so it's no huge leap to begin actively engineering that bacteria to suit our metabolic needs.
The new research was published in the journal PNAS.
Source: Baylor College of Medicine