This research proposes a new method by which our T cells are taught to live with our normal microbiota. The scientists have conducted a complex series of experiments on genetically altered mice, to allow them to learn about T cell-bacteria interactions. In this system, some T cells, rather than being taught in the thymus, are educated directly by the microbiota in the colon, and this teaches them not to attack the bacteria, but to tolerate them. Intriguingly, it was shown that when this education did not occur, the mice developed colitis. While this is a mouse model only, it is a new concept in bacteria-human interactions in the gut, and may have profound implications for IBD research and future therapies.

In this study adults with Crohn’s either continued maintenance infliximab or were switched to adalimumab. Patients were studied for one year to find out how many preferred adalimumab and also how many needed extra treatment or had to stop their existing treatment due to side effects.

The study was stopped early because of safety concerns within the patients being switched to adalimumab. More patients in the adalimumab group had loss of response or intolerance than those continuing infliximab. However those patients that received adalimumab preferred their treatment.

Overall this study found that in patients whose remission is maintained by infliximab, switching to adalimumab is worse than continuing infliximab even though patients preferred adalimumab. Adalimumab is often used as a second-line treatment in patients who have stopped responding to infliximab, which is a somewhat different and entirely accepted clinical situation supported by previously published evidence.

This enormous study looked really closely at differences in the over 50 specific areas of the genome in 350 patients with IBD and 350 healthy people. They then went on to ‘double-check’ their findings in over 45,000(!) people. They got some really interesting results, finding new differences in old genes (such as NOD2 – see last month’s blog entry) and some exciting differences in unexpected places.

Altogether this study will really help us understand some of the ways in which changes in our DNA could lead to changes in the bowel and subsequently IBD – which can only be a positive thing!

Interestingly the probiotic yoghurts were not entirely ineffectual and did influence the switching on of genes within the resident bacterial community, particularly with relevance to the breakdown of carbohydrates (sugars and starches). Why this occurred is not clear. Sufficed to say if probiotic yoghurts are effective in humans, it probably isn’t because their bacteria colonise the gut in large proportions or alter its overall composition, but by more subtle means. They may well have little to no practical effect in healthy people and their benefits in most variants of IBD remain to be proven.

It is noteworthy that this study was part-sponsored by Danone and published despite its potentially detrimental effect on their industry.

The evening starts at 7.30pm and advance tickets will be available from Pavilion Electrics, Keymer Road, Hassocks or by ringing 01273 845291 – on sale from Monday 27th February.

Why not go along, support this new venture and have your questions answered ready for the spring/summer gardening sessions.

If you are a parent/carer of a child or young person with Crohn’s Disease or Ulcerative Colitis and live in the Bristol area you are invited to join this informal event where there will be an opportunity to meet members of the medical profession from Bristol Children’s Hospital and other guest speakers. There will be ample opportunity to meet and chat with other families in a similar situation to yourselves, and also meet to the CICRA team. Refreshments and lunch will be provided. A map of the venue can be found on the Armada House website (www.armadahouse.co.uk).

We are still finalising the programme, but we can tell you that during the morning there will be easy to understand talks about medical subjects and a presentation from a young person with Crohn‘s and another with Ulcerative Colitis. After the lunchtime break there will be a number of parallel mini sessions, each group headed up by one or two specialists. Families will be able to move freely between the groups that interest them the most. We expect to cover a good range of topics, some of which are listed below and generally there will be time to join in three of these interactive groups.

1. Research – what’s new?
2. Transition/Education
3. Nutrition and Diet
4. Living and coping with IBD

At the same time there will be a separate group for the younger children and a special group for teenagers but they can, of course, stay with parents if they wish.

If you would like further information or to register your interest please ring the CICRA office on 020 8949 6209

Alternatively you can contact us from this site stating:

Your name and address, the Hospital the child/young person is attending, and the ages of all those in your party under the age of 18.

Please also advise the total number of people wishing to attend meeting and the number requiring buffet lunch.

NOTE: There are limited places available so if you email your interest you will receive an email by return confirming your place/s if they are still available.

All of your favourite pages such as the bulletin boards (renamed “Member Forums”) and a specific area dedicated to our younger visitors (the “Cool Zone”) remain available.

Please feel free to browse around the site. If you have any feedback or questions for us click here for contact details.

This paper from researchers in Germany, USA and Ireland focuses on E. faecalis, one of its enzymes and their relationship to an IBD-like change in mice known to be prone to an IBD-like disease. 60% of E. faecalis strains produce a powerful protein-digesting enzyme called gelatinase. This can result in damage to important structures of the gut in healthy hosts which act as barriers against invading bacteria. The researchers used E. faecalis strains both with and without the ability to produce this enzyme and introduced them to mice with impaired immune systems and no other gut bacteria (“germ-free” mice) to determine how much IBD-like inflammatory change was produced. Intestinal inflammation was most apparent in germ-free mice exposed to E. faecalis with the ability to produce gelatinase. Germ-free mice exposed to strains unable to produce this enzyme had a mild degree of inflammation only. Interestingly, when E. faecalis was given to mice with normal gut bacteria (“wild-type” mice), no inflammatory response was seen.

This study shows that in the correct conditions (in this case mice with an impaired immune system and no gut bacteria) that E. faecalis can cause inflammatory change but that this is intensified if it is able to produce a specific enzyme and hence disrupt the normal barriers of the gut. If any of these 4 steps were altered (mouse immunity, mouse gut bacteria, E. faecalis, ability to produce enzyme) the inflammation either did not occur or was less intense. In humans a similar set of circumstances may be necessary for the development of IBD; however our knowledge of the required steps is limited. Studies such as this in a simplified mouse model of IBD allow the exploration of single steps, one-at-a-time, which can inform and improve our understanding of human IBD.

RH

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