Thursday, 4 December 2014

Gut dysbiosis in treated coeliac disease: time for a probiotic or worse?

"Our findings indicate that dysbiosis of microbiota is associated with persistent gastrointestinal symptoms in treated celiac disease patients and open new possibilities to treat this subgroup of patients."

That was the summary of the paper published by Pirjo Wacklin and colleagues [1] who looked at the bacterial constitution of the duodenal microbiota [the bacteria which inhabit us] in a small group of participants diagnosed with coeliac (celiac) disease who "had been following a strict GFD [gluten free diet] for several years and had restored small bowel mucosa and negative celiac autoantibodies." Based on an analysis of bowel symptoms recorded using the Gastrointestinal Symptom Rating Scale, researchers reported that despite the use of a gluten free diet - universally indicated for coeliac disease (CD) - a proportion of their cohort still presented with "persistent symptoms" and it is within this cohort they were aiming to see whether: "abnormal intestinal microbiota may be associated with persisting gastrointestinal symptoms in treated celiac disease patients."
I'm applying for a villain loan. I go by the name of Vector.

"The treated patients with persistent symptoms had a higher relative abundance of Proteobacteria (P=0.04) and a lower abundance of Bacteroidetes (P=0.01) and Firmicutes (P=0.05)." That and "their microbial richness was reduced." All of this led authors to conclude that for some with CD, a gluten free diet might just be the start of a management schedule to alleviate symptoms and improve quality of life.

This is not the first time that CD (both treated and untreated) has been discussed with the gut microbiome in mind. The paper from De Palma and colleagues [2] (open-access) hinted that there may be more to see based on analyses of fecal samples for IgA-coated bacteria compared to results from asymptomatic controls. Granted the results do not directly overlay with the recent Wacklin findings but it's a start at least. Likewise the paper from Sellitto and colleagues [3] (open-access) (covered in a previous post on a sister blog) might also be pertinent to add to the discussion with their findings of "significant differences between the developing microbiota of infants with a genetic predisposition for CD and those from infants with a non-selected genetic background." I might add that the delayed introduction of gluten bit to their paper has not seemingly been borne out by subsequent larger scale research (see here).

Then to the next question leading from the Wacklin results: do issues with gut bacteria mean that altering gut bacterial communities might be an intervention option? Well, one might certainly consider something like the use of probiotics to try and 'change' the bacterial make-up as a possibility. Indeed, type 'probiotics and celiac disease' (non-UK spelling) into PubMed and you get an array of papers talking about how probiotics might already have a role for some with CD. I've previously talked about the paper from Sarno and colleagues [4] on this blog (see here) and "a novel effect of probiotics in the prevention of undigested gliadin peptides toxic effects". Tomorrow on this blog, I have a post scheduled tomorrow about the paper from Duar and colleagues [5] on probiotics potentially degrading gluten peptides. One might also entertain the possibility that certain probiotics might also affect related systems such as abnormal intestinal permeability too...

Insofar as probiotics potentially affecting GI symptoms in CD, the paper by Smecuol and colleagues [6] provides some preliminary data suggesting that there may be more to see in this area. Based on their examination of "the probiotic Bifidobacterium natren life start (NLS) strain", authors concluded that under placebo-controlled conditions: "those randomized to B. infantis experienced a significant improvement in Gastrointestinal Symptom Rating Scale (P = 0.0035 for indigestion; P = 0.0483 for constipation; P = 0.0586 for reflux)". And yes, their results were based on the same Gastrointestinal Symptom Rating Scale used by Wacklin and colleagues.

Rather more speculatively, and with specific regard to the the 'or worse' bit of the title of this post is another possible means that one might think about altering the gut microbiota: the fecal microbiota transplantation or stool transplant. Now just before anyone gets the wrong idea here, I'm not talking about some sort of DIY transplant for CD as per other media reports (see here). What I do think is worthwhile however is for some brave researcher(s) to perhaps entertain the idea that transplanting bacteria from one person to another might have some potentially important effects in cases of CD as per it's use in other areas of medicine (see here) and onwards think about putting some actual science to the anecdotes. I'll say no more on this matter (at least for now).

Music to close: Roxanne by The Police.

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[1] Wacklin P. et al. Altered Duodenal Microbiota Composition in Celiac Disease Patients Suffering From Persistent Symptoms on a Long-Term Gluten-Free Diet. The American Journal of Gastroenterology. 2014. November 18.

[2] De Palma G. et al. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 2010 Feb 24;10:63.

[3] Sellitto M. et al. Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants. PLoS ONE. March 2012.

[4] Sarno M. et al. Lactobacillus paracasei CBA L74 interferes with gliadin peptides entrance in Caco-2 cells. Int J Food Sci Nutr. 2014 Jul 17:1-7.

[5] Duar RM. et al. Identification and characterization of intestinal lactobacilli strains capable of degrading immunotoxic peptides present in gluten. J Appl Microbiol. 2014 Nov 6. doi: 10.1111/jam.12687.

[6] Smecuol E. et al. Exploratory, randomized, double-blind, placebo-controlled study on the effects of Bifidobacterium infantis natren life start strain super strain in active celiac disease. J Clin Gastroenterol. 2013 Feb;47(2):139-47.

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ResearchBlogging.org Wacklin, P., Laurikka, P., Lindfors, K., Collin, P., Salmi, T., Lähdeaho, M., Saavalainen, P., Mäki, M., Mättö, J., Kurppa, K., & Kaukinen, K. (2014). Altered Duodenal Microbiota Composition in Celiac Disease Patients Suffering From Persistent Symptoms on a Long-Term Gluten-Free Diet The American Journal of Gastroenterology DOI: 10.1038/ajg.2014.355