The balance of microorganisms found in our intestine is essential for good health, and alterations in this population of microbes (intestinal dysbiosis) have been associated with various diseases, and even mental disorders such as depression. Harmful bacteria can inflame the colon and lead to colitis.
It is known that probiotics can help maintain a healthy gut microbiome and restore the population of “good bacteria” after antibiotic treatment, for example, but now a study has shown that they could also be used as an effective therapeutic strategy for combat intestinal pathologies, such as Crohn’s disease.
The research has been carried out by scientists from the Chinese National Academy of Science who have developed a microgel delivery system for probiotics that keeps the “good” bacteria protected while actively killing the “bad” ones. This system has been tested in mice, in which it treated intestinal inflammation without causing side effects, as shown by the results published in ACS Central Science.
One of the symptoms of inflammatory bowel disease and Crohn’s disease, among others, is chronic colitis. Currently these pathologies are treated with immunosuppressants, but they can cause bacteria to become resistant to antibiotics. An alternative strategy is to administer beneficial bacteria, or probiotics, to help restore balance to the gut microbiota, but for a treatment to reach the colon, it must first resist stomach acids, withstand removal from the gut, and fight for space with bacteria. numerous invading bacteria.
A treatment with probiotics to rebalance the microbiota
Combining probiotics with a drug delivery system could make this strategy feasible, although most current approaches are limited to protecting probiotics from digestion without influencing the microbes responsible for the condition. Zhenzhong Zhang, Junjie Liu, Jinjin Shi and their colleagues then decided to combine probiotics with specially designed microgel beads to keep the good bacteria safe while actively helping to kill off the bad.
To develop this system, the researchers combined sodium alginate, tungsten, and calcium-containing nanoparticles into small spherical microgels, then coated them with beneficial probiotic bacteria. The gels protected the bacteria as they moved through the stomach and increased their retention time in the colon. Once there, the calprotectin proteins, highly expressed during colitis, bound to the calcium and broke down the gels, allowing the tungsten to come out. By displacing molybdenum in a key enzyme substrate of the bad bacteria Enterobacteriaceae, tungsten inhibited the growth of the microbe without affecting the probiotics.
The researchers carried out experiments with a mouse model of colitis, and the system allowed the probiotics to proliferate in the intestine without causing side effects. Furthermore, the mice with the microgel beads did not display many of the characteristics of colitis, such as shorter colons or impaired intestinal barriers, demonstrating that the delivery system could be a viable treatment strategy. Although their utility still needs to be demonstrated in more advanced preclinical models, the researchers say this work offers a new perspective on treatments using colonizing probiotics.
.