Published: 27th May, 2013
Authors: Taha Rashid, Clyde Wilson, A. Ebringer

This paper explores the link between the microbe Klebsiella and ankloysing spondylitis (as well as Crohn’s disease).

Specifically it analyses the source of this microbe’s food, what it needs to grow and replicate in the body.

Studies have found that the amount of Klebsiella found in individuals on a “high carbohydrate/low protein diet” is significantly higher that those on a “low carbohydrate/high protein diet.” 40 times higher according to one study.

Abstract:

“Both ankylosing spondylitis (AS) and Crohn’s disease (CD) are chronic and potentially disabling interrelated conditions, which have been included under the group of spondyloarthropathies.

The results of a large number of studies support the idea that an enteropathic pathogen, Klebsiella pneumoniae, is the most likely triggering factor involved in the initiation and development of these diseases.

Increased starch consumptions by genetically susceptible individuals such as those possessing HLA-B27 allelotypes could trigger the disease in both AS and CD by enhancing the growth and perpetuation of the Klebsiella microbes in the bowel.

Exposure to increased levels of these microbes will lead to the production of elevated levels of anti-Klebsiella antibodies as well as autoantibodies against cross-reactive self-antigens with resultant pathological lesions in the bowel and joints.

Hence, a decrease of starch-containing products in the daily dietary intake could have a beneficial therapeutic effect on the disease especially when used in conjunction with the currently available medical therapies in the treatment of patients with AS and CD.”

Introduction:

“… Both AS and CD affect early age groups and have a world-wide distribution. There are at least one million individuals in the United Kingdom who suffer from some features of AS.

The negative impact of AS on the employment and the psychological status of patients with this disease has been well established.

The disease in CD can also have an impact on the social status and work abilities of patients, especially in women. Because of these negative impacts on the general health and welfare status of patients with AS and CD, with certain drawbacks of the currently used medical treatments, a search for the causative factor and an alternative therapeutic measure involving eradication of the cause could be helpful in the management of patients with these diseases.”

Genetic Background of AS and CD

“A positive family history is one of the key points in defining the characteristics of patients with SpA. In a family study of AS probands and healthy controls in an Icelandic population, it has been shown that there is evidence which might support the existence of common genetic components for AS and IBD.

The study demonstrated a risk ratio of 3.0 and 2.1 in the first and second-degree relatives, respectively, for the occurrence of AS in families of probands with IBD, and with the occurrence of IBD in families of patients with AS.

In a more recent study, it has been shown that there is genetic overlap across the autoimmune diseases including also AS and IBD. It appears, therefore, that certain common genetic factors might act in the development of both diseases in AS and CD.

The frequency of association of HLA-B27 allelotypes in patients with AS is considered as the strongest genetic link with any disease which have been encountered in the field of rheumatology.

This genetic bond was discovered in the early 1970s, where more than 95% of patients with AS have been found to possess HLA-B27, whilst the frequency of this gene in the general population was below 10%.”

Klebsiella and AS

“… Various immunological studies carried out by independent groups from 16 different countries have shown that antibodies against K. pneumonia and/or cross-reactive self-antigens but not against other microorganisms are significantly elevated among patients with AS when compared to patients with other diseases or to healthy individuals.

Levels of anti-Klebsiella antibodies were found to be significantly higher in the serum than in the synovial fluid samples taken from AS patients. The sources of these antibodies are from extra-articular regions such as the lymph nodes draining the gut.

Serum samples taken from active AS patients were found to possess significant in vitro cytotoxic activities when compared to sera taken from patients with RA or healthy controls. Increased percentage of lysis is present in sheep red blood cells which have been coated with Klebsiella cross-reactive antigens such as HLA-B27 synthetic peptides, QTDRED.

Antibodies to Klebsiella nitrogenase reductase peptides, QTDRED, were shown to bind preferentially to the synovial tissues of AS patients when compared to those from patients with other rheumatic diseases.

Klebsiella bacteria have been isolated by different independent groups more significantly from the bowel of active AS patients when compared to controls.

These findings, however, were not confirmed by other groups. The discrepancies in these results could be explained by the differences in the methods of collections and cultures of the faecal specimens and the disease activity status.

Furthermore, in a study by a group from Finland it was shown that elevated levels of IgA anti-Klebsiella antibodies in patients with AS correlated with the degree of gut inflammation.

It is well documented that there is a strong link between gut inflammation and/or AS. The level of total and secretory IgA immunoglobulins increased in the majority of patients with AS.

Moreover, there is evidence for elevated levels of IgA, particularly secretory IgA antibody against Klebsiella antigens or Klebsiella cross-reactive antigens in active patients with AS. The results of these studies linking Klebsiella, collagen, and HLA-B27 to AS could explain some of the predominant characteristic clinical, genetic, and immunological features present in the patients with this disease.”

Starch and Gut Microbes

“The main substrate that is necessary for the growth of colonic microbial agents includes starch and complex carbohydrates which are usually available in considerable amounts in the bowel.

In a study, carried out by a group from Minnesota, using hydrogen breath tests as an index of carbohydrate absorption in healthy individuals, up to 20% of a test meal of starch was found to be available for metabolism by the colonic microflora.

It has been found also that up to 10%, of consumed starch can escape the absorption in the small bowel, indicating that a considerable proportion of dietary starch reaches the large intestine.

In another experimental study it has been shown that a significant increase in the total bacterial population of enterobacterial microbial agents was noticed in the faeces of rats which have been fed diets containing resistant potato starch when compared to those taking rapidly digestible waxy maize starch…

… Klebsiella can survive in harsh environments exploiting some of its enzymatic degrading products, which are required for the protection, maintenance and survival of these microbes…

… A fraction of the total dietary starch consumed daily in humans resists digestion by pancreatic amylase in the small intestine, thereby, reaching the colon.

This form of undigested or resistant starch is usually fermented by human gut microflora, providing a source of energy and carbon for more than 400 species of bacteria present in colon.

A group from Los Angeles had shown that the mean number of faecal Klebsiella concentrations in individuals taking high carbohydrate/low protein diet was forty times higher than in those having low carbohydrate/high protein diet.

Similarly, the mean number of Klebsiella was found to be ten times higher when incubated with simple carbohydrate products such as sucrose, lactose, and glucose than with eleven different amino acids.

These results indicate that complex carbohydrates such as starch-containing products are necessary for the growth, replication, and persistence of many enterobacterial agents including Klebsiella microbes in the large bowel.”

Potential for the Use of Low Starch Diet in AS and CD Patients

“The current medical therapeutic agents used in patients with AS and CD include nonsteroidal anti-inflammatory and immunosuppressive drugs, as well as biological agents.

These treatments, however, cannot reverse the existing destructive spinal lesions and might be associated with deleterious side effects.

Therefore, implementation of other therapeutic measures especially those involving the means for effective eradication of the causative agents by using a low starch diet intake and possibly antibiotics together with the currently used medical treatments could have a beneficial effect in the management of patients with AS and CD.

These data support the causative effect of high starch consumption and the beneficial effect of low starch intake in patients with SpAs, especially those with AS or IBD. For example, in a previous study on a group of UC patients, analyses of the contents of surgically removed ileocaecal regions have shown that the ileostomy fluid contained significant amount of monosaccharides and disaccharides.

These simple carbohydrate products detected in the ileostomy fluid would appear to be derived from starch. In another prospective longitudinal study, the influence of dietary factors was examined in a group of Italian patients with IBD and a group of healthy controls well matched for age, sex, and location of living.

The results showed that patients with CD and UC have an increased consumption of the total carbohydrate and starch with a significantly higher relative risk compared to healthy individuals.

In a later review analysis of the literatures on the daily intake of diets and their relation to intestinal microbial flora in patients with IBD, it was shown that a considerably large amount of data show an association between increased intake of westernized carbohydrate food, high intestinal microbial load, and the occurrence of IBD.

In a longitudinal open study carried out in a group of 36 patients with active AS in “London AS Clinic,” most of the patients had shown reductions in their erythrocyte sedimentation rates and total IgA concentrations, as well as a drop in their intake for the anti-inflammatory medicines after a nine-month followup following a decrease the dietary intake of starch.

It appears that in both IBD and AS, an interaction between the gut microflora and the mucosa is a possible contributor to the development of these diseases.

These data results support the notion that an increase in the bulk of potentially pathogenic organisms such as Klebsiella in the faecal microflora due to high starch consumption could help in the initiation and development of both AS and CD.

It seems, therefore, that an exclusion of a diet containing complex carbohydrates such as starch, but not simple carbohydrate-containing foods such as glucose or sucrose, might inhibit the growth of Klebsiella and could ameliorate the disease process and activity in patients with AS and CD.”

Conclusions

“AS and CD are shown to be two interrelated conditions mainly based on the existing genetic and immunological features.

The main pathogenetic mechanism which can explain this linkage is “molecular mimicry” or “cross-reactivity” between Klebsiella pneumonia and target tissues.

It appears that starch is the main source of Klebsiella growth in the colon. Hence, increased consumption of starch-containing foods by genetically susceptible individuals such as those possessing HLA-B27 genes could result in the initiation and development of AS or spondylitis-associated CD.

Dietary manipulation in the form of low starch diet intake can be included in the management of patients with AS or CD, especially when used in conjunction with the current medical therapeutic measures.”