This week: anti-TNFα treatment shows promise in early Crohn’s disease, rifaximin takes on over-sensitive gut nerves and mast cells might be behind stress-induced tummy troubles.
Hit Them Early and Hit Them Hard
Specialists treating newly diagnosed cases of Crohn’s disease (CD) in children usually follow a specific treatment regimen: corticosteroids followed by immunomodulators, like azathioprine. However, scientists funded by the Crohn’s and Colitis Foundation of America wondered if better results could be obtained with another protocol, a protocol including early use of anti-TNFα. In a huge collaborative study using patients that were matched for age and disease severity, CD severity was followed for a year after initial treatments. It was discovered that early treatment with anti-TNFα led to a significantly better clinical and growth outcomes than the typical regimen.
Rifaximin Settles Gut Nerves
Some intestinal disturbances, including irritable bowel syndrome (IBS), can be attributed to what is called “visceral hyperalgesia,” a situation of heightened nerve sensitivity. The antibiotic rifaximin has shown promise for IBS treatment, but little was known about its mechanism. Using two visceral hyperalgesia models in rats based on chronic stress, scientists from the University of Michigan determined that these models were associated with alterations in the microflora, increased intestinal permeability and mucosal inflammation. Rifaximin, unlike a control antibiotic, eliminated these dysfunctions. The benefits appeared to be linked to an increase in beneficial bacteria species in the gut after treatment that was not found after other kinds of antibiotic treatment.
Mast Cells Behind Nervous Gut Permeability
Most of us are familiar with nervous gut trouble, especially when we have to speak in front of a crowd. Belgium scientists suspected that corticotropin-releasing hormone (CRH) could be playing a role in stress-induced gut permeability. After administering CRH to volunteers, they found changes in gut permeability similar to those found after public speaking. One target of CRH is the mast cell, which has all of the right tools to cause a good case of tummy trouble. To find out if the mast cell could be the culprit behind stomach butterflies, they asked volunteers to take the mast cell blocker disodium cromoglycate and either give a presentation or take CRH. Blocking mast cells alleviated intestinal permeability in both situations.
This week we find new ways that bacteria interact with the gut, aluminum looks like a deadly suspect in inflammatory bowel disease and parasitic worms seem to have their own T helper subset.
Bacteria Escapism in Crohn’s Disease Revealed
Adherent-invasive Escherichia coli (AIEC) are found in Crohn’s disease (CD) patients and are able to aggravate inflammation. Control of these kinds of bacteria requires functional autophagy, which destroys intracellular pathogens. Researchers from the University of Auvergne in France have now discovered that AIEC protect themselves from destruction by manipulating the genes needed to control autophagy. This was achieved by an upregulation of microRNAs designed to inhibit ATG5 and ATG16L1 expression. Blocking the microRNAs restored autophagy and reduced inflammatory responses. This mainly in vitro study suggests that restoring autophagy in CD may lead to lowered inflammation.
Aluminum: New Culprit in Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) incidence has risen simultaneously with industrialization and the emergence of modern society. This suggests that environmental pollutants may cause IBD. One possible guilty suspect is aluminum, which is known to be associated with abnormal immune function. To determine if aluminum was involved with intestinal inflammation, scientists from France administered aluminum to three types of murine IBD models. They found that aluminum worsened disease severity in each model, impaired intestinal barrier function and directly increased cellular immune responses.
Parasitic Worms Get Their Own T Cell Subset
Parasitic worms are now being investigated in clinical trials as a possible way to treat IBD. Research investigating the immune response generated by parasitic worms would be helpful for refining these studies. A current publication in Immunity does just this by examining T cell responses and the clearance of Nippostrongylus brasiliensis, a worm similar to Necator americanus used in the mouse IBD studies. They found that interleukin-9 producing T cells (Th9) were essential for worm clearance and the induction of T helper 2 cytokines. An interesting research question would be to determine if Th9 is involved in the therapeutic effect of parasitic worms in IBD.
Pathogens Plunder the Gut after Antibiotic Treatment
Antibiotic treatment is associated with IBD development. In general, this is likely associated with the resultant changes in the microbiota and also the entrance of enteric pathogens. Finding ways to use antibiotics safely could prevent some cases of IBD. A research team from Stanford has brought us one step closer by clarifying how some enteric pathogens thrive after antibiotic treatment. They found that the availability of bacterial sugars after antibiotics is part of the problem. Normal microbiota “harvest” sugars attached to the mucus for food. However when antibiotics are applied, surviving Salmonella typhimurium and Clostridium difficile quickly utilize the free sugars to grow and thrive.