Genetically engineered bacteria could help in Crohn's and colitis

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IBD conditions are serious ailments in which the gut becomes inflamed and damaged, sometimes so severely that surgery to remove the inflamed sections is the only treatment currently available. The conditions arise when the immune system attacks the gut, for reasons that are poorly understood. Symptoms include cramps, ulcers, weight loss, diarrhea, and the inflammation can result in intestinal scarring and a greater risk of developing bowel cancer. The study, led by Jean-Paul Motta of the Centre de Physiopathologie de Toulouse Purpan (CPTP) in Toulouse, France, genetically modified two strains of Lactobacillus bacteria by splicing a gene into their DNA that instructs cells to manufacture the naturally-occurring protein, elafin, which the team had noted was deficient in patients with IBD. The bacteria are probiotic and do not cause harm in humans. Elafin blocks the actions of members of the protease group of enzymes, which are known to play a role in inflammation. It is expressed in the skin and lungs during healing of trauma. As reported in Phys.org elafin is also now known to be a marker that can be measured by a blood test to determine whether or not skin graft patients will be susceptible to graft-versus-host disease (GVHD). In earlier studies the French and Canadian team of researchers had shown that mice genetically engineered to manufacture more elafin were afforded protection against a condition similar to human colitis. In the new study they aimed to find out if increasing the levels through the use of probiotic bacteria would also protect against inflammation. The research team fed the bacteria to mice and found that the levels of elafin increased to greater levels than in control mice fed non-genetically engineered bacteria of the same strains. They induced IBD in the mice and found that those fed the bacteria with the elafin gene had greater resistance, and that there was less inflammation and cell damage. They also reported a reduction in the numbers of neutrophil and macrophage immune cells in the gut. The researchers also added the bacteria to cultures of gut tissue from human IBD patients and reported that the key signs of inflammation were reduced in the presence of the elafin-manufacturing bacteria. The study findings, reported this week in Science Translational Medicine, suggest that the bacteria could be of benefit to IBD patients, and could be given in pill form or alternatively, the food-grade bacteria could be added as live cultures to yogurts. More research is needed to ensure the best strains of bacteria are selected and to ensure the safety and efficacy of the treatment in human patients.

I remember reading about this before on these boards.

How do they induce IBD in mice when they don't know the cause of IBD?

I think they have identified genes that, when removed (kmocked out) from mice, cause them to get an IBD like intestinal infllammation once their guts are exposed to normal intestinal bacteria (if kept sterile they dont get IBD)- but indeed, humans are not mice so that may explain at least a big chunk of why studies never pan out as much in practice as in theory.

I too am cautious about the DSS-colitis and the knockout colitis used in mouse models.

I think it is wrong to say they "don't know the cause of UC" - they know plenty. It will help you to think in more complex ways. They know it is a combination of genetic (and epigenetic), gut microbe health, and environmental triggers. They know a lot about the sequence of chemical messages and regulation that leads to inflammation and tissue damage, and they know how permeability of the mucosa can trigger certain immune responses.

Just because it is not clear why the dominos start to fall, or if it is always for the same reason, doe not mean they they do not know a lot about how the dominos fall, and which fall in what order. In mice/research they can artificially start the dominos falling at some point and study. Pharmaceuticals and natural substances (mostly anti-oxidants and anti-inflammatory, but also some specific receptor blockers such as nicotine) in fact seem to stop the dominos before all have fallen. They start to fall, but something has increased the gap a bit at some point, so the next one along does not fall.

Some people here like to say "they don't know crap", or "they know absolutely nothing" - but these are ridiculous statements. I think they are expressions of frustration. While there are some arrogant and stodgy doctors, I think a lot of doctor bashing (and declaring them to be ignorant or dumb asses) is a means of feeling some control (i.e., coping).

BTW, I am all for engineered bacteria. A year or so back someone dropped in here to talk a bit about her research to genetically manipulate the expression of ALA on the surface of bacteria to study how bacteria "talked" to the immune system. IMO, great research.

For the win? I think the induce colitis in mice with hydrogen peroxide... sounds lovely, but not exactly what we have, nor are we mice.