Hello all,
Recently I have been studying bacteria and chronic infections via a course offered the University of Copenhagen. This course does not focus on IBD, but I have nevertheless found much interesting and useful information about it, and would like to share it with you all.
The first thing is the simple idea that Crohn's and other forms of IBD could involve chronic wounds. Wounds inside the body are usually referred to as ulcers, but they are still technically a form of wound. A chronic wound is defined as an external or internal injury that does not heal for 3+ months. As we often see that Crohn's patients have ulcers during colonoscopies with 6+ months between them, I believe it is worth investigating whether or not these specific ulcers persist, or whether there is a high turnover and there are simply new ulcers forming constantly. If ulcers inside the intestines have a tendency to last, we may be dealing, in part, with a biofilm problem.
Biofilms are congregates of bacteria, usually many different types, that group up and start employing strategies that allow them to persist in a host. In the case of someone who has had a knee replacement, we can at times find biofilms adhering to the foreign material of the implant. This biofilm is less virulent than planktonic (free floating) bacteria, but it is very resistant to antibiotics. Furthermore, there are molecules bacteria use in quorum sensing that upregulate the mutability of bacteria in the film, meaning that the bacteria are able to evolve antibiotic resistance more rapidly. And because of the physiological characteristics and oxygen tension of the biofilm, only small amounts of most antibiotics are able to penetrate anyway. Unfortunately, these factors combined mean that biofilms are the perfect breeding ground for antibiotic resistance, and this antibiotic resistance could potentially be passed on to future bacteria entering our bodies, via plasmids - so not only are the current bacteria in your gut becoming resistant, but future bacteria in your gut could be resistant, too. For those unfamiliar, a plasmid is a discrete section of DNA bacteria can give each other which can confer a variety of traits - antibiotic resistance being just one.
Please note, biofilms can be found all over the body, even in soft tissues without any foreign implant. In cases like these, the bacteria do not so much adhere to a surface, but adhere to each other.
In summary, I believe work should be done to investigate the nature of ulceration in Crohn's/IBD. If we find that ulcers in these diseases are actually persisting, then work should be carried out to make sure the problem of biofilms is addressed.
Funnily enough, one of the methods of overcoming biofilms is the use of triple-antibiotic therapy, exactly like the treatment being investigated by RedHill Biopharma. Some other methods could be the use of enzymes to lyse the polysaccharide network holding the biofilm together, use of molecules to disrupt the quorum sensing of the film, physical removal of the film (in IBD, this would be a resection, but could also be a more friendly debridement), and more. I am concerned that biofilms may be part of the reason inflammatory bowel diseases are chronic.
Recently I have been studying bacteria and chronic infections via a course offered the University of Copenhagen. This course does not focus on IBD, but I have nevertheless found much interesting and useful information about it, and would like to share it with you all.
The first thing is the simple idea that Crohn's and other forms of IBD could involve chronic wounds. Wounds inside the body are usually referred to as ulcers, but they are still technically a form of wound. A chronic wound is defined as an external or internal injury that does not heal for 3+ months. As we often see that Crohn's patients have ulcers during colonoscopies with 6+ months between them, I believe it is worth investigating whether or not these specific ulcers persist, or whether there is a high turnover and there are simply new ulcers forming constantly. If ulcers inside the intestines have a tendency to last, we may be dealing, in part, with a biofilm problem.
Biofilms are congregates of bacteria, usually many different types, that group up and start employing strategies that allow them to persist in a host. In the case of someone who has had a knee replacement, we can at times find biofilms adhering to the foreign material of the implant. This biofilm is less virulent than planktonic (free floating) bacteria, but it is very resistant to antibiotics. Furthermore, there are molecules bacteria use in quorum sensing that upregulate the mutability of bacteria in the film, meaning that the bacteria are able to evolve antibiotic resistance more rapidly. And because of the physiological characteristics and oxygen tension of the biofilm, only small amounts of most antibiotics are able to penetrate anyway. Unfortunately, these factors combined mean that biofilms are the perfect breeding ground for antibiotic resistance, and this antibiotic resistance could potentially be passed on to future bacteria entering our bodies, via plasmids - so not only are the current bacteria in your gut becoming resistant, but future bacteria in your gut could be resistant, too. For those unfamiliar, a plasmid is a discrete section of DNA bacteria can give each other which can confer a variety of traits - antibiotic resistance being just one.
Please note, biofilms can be found all over the body, even in soft tissues without any foreign implant. In cases like these, the bacteria do not so much adhere to a surface, but adhere to each other.
In summary, I believe work should be done to investigate the nature of ulceration in Crohn's/IBD. If we find that ulcers in these diseases are actually persisting, then work should be carried out to make sure the problem of biofilms is addressed.
Funnily enough, one of the methods of overcoming biofilms is the use of triple-antibiotic therapy, exactly like the treatment being investigated by RedHill Biopharma. Some other methods could be the use of enzymes to lyse the polysaccharide network holding the biofilm together, use of molecules to disrupt the quorum sensing of the film, physical removal of the film (in IBD, this would be a resection, but could also be a more friendly debridement), and more. I am concerned that biofilms may be part of the reason inflammatory bowel diseases are chronic.
