For now consider this:

"Researchers in London have discovered that a weak immune response instigates Crohn's disease, possibly laying to rest the popular belief that an auto-immune condition is to blame”. (Link.)

The conclusions of this study do not seem to support auto-immunity or an overly aggressive response to MAP as the underlying cause of CD. However, the conclusions do FULLY support my hypothesis below.

For many years there have been generally two camps for Crohn’s researchers/experts: those who support auto-immunity (genetic predisposition) and those who support MAP-infection as the primary causative factor of CD… but, perhaps it’s a combination of MAP, genetic predisposition (a weak immune response to MAP) and diet that leads to Crohn's??? More details on my new blog!

Additionally, I’d like to say many thanks for all your supportive emails and kind words!

Mycobacterium avium subspecies paratuberculosis, or MAP for short, is the organism responsible for a chronic, intestinal inflammatory disease found mainly in domestic livestock, including cattle, deer, sheep and goats.

MAP was first described in 1895 by Dr H. A. Johne and Dr L. Frothingham after they observed the bacteria throughout the inflamed intestinal-tissues of a cow that failed to gain weight or produce milk. And the disease has since become known as Johne’s disease (JD) or paratuberculosis.

Even though a herd of cattle may become infected with Mycobacterium avium subspecies paratuberculosis (MAP), usually only a small percentage develop clinical signs of the disease, which is often characterized by profuse diarrhoea and severe weight loss. And, as the disease advances, animal death inevitably follows.

Paratuberculosis was long considered a disease of domestic ruminants only. But significant research over the last decade or so has seen MAP isolated from many different animals and numerous species. However, observation and study data suggests MAP primarily expresses clinical disease in domestic livestock (especially dairy cattle).

If you are new to MAP and Johne’s disease, and want to learn more about them, visit one or more of the pages listed below.

• Johne’s FAQs
• History of Johne’s disease
• Articles and brochures
• True cases and stories
• Biology of MAP

A growing number of studies have found MAP in the intestines Crohn’s disease (CD) patients. And therefore it’s been proposed that MAP may be a major cause CD too. If you are unfamiliar with Crohn’s disease, one or more of the sites below will provide a brief introduction to the disease.

• National Digestive Diseases Information Clearinghouse
• Crohn’s and Colitis Foundation of America
• Crohn’s and MAP infection

How MAP causes disease is simply unknown, but, it’s assumed MAP somehow initiates an immune-system response from susceptible hosts (cattle, sheep, deer, etc) and their immune responses may, in some way, lead to inflammation, pathological lesions and ulceration. In other words, it’s assumed that susceptible hosts’ immune responses to MAP cause gut inflammation by erroneously ‘attacking’ their own intestinal tissues.

However, I’m proposing the above assumption is wrong. I’m proposing MAP directly causes tissue damage observed in MAP-infected hosts, and their immune systems respond to the tissue damage, and not the other way round!

Below is a hypothesis which details my personal view of how Mycobacterium avium subspecies paratuberculosis may cause disease including:

• How MAP may survive the antibacterial compounds of and kill macrophages. (It’s very unlikely to be related to extra-cellular toxins because none have ever been discovered.)
• Why MAP almost exclusively expresses clinical disease in domestic ruminants. There have been a small number of documented cases of clinical paratuberculosis in wildlife but that number is insignificant in contrast to the potentially vast number of cattle that have developed clinical Johne’s disease over the last few decades.
• Why dietary calcium may reduce MAP infection in Beige mice.
• Why acidic soil-types seem to favour Johne’s disease expression in cattle, and alkaline soil-types seem to retard disease expression. And, why the application of lime to grazing pastures may limit Johne’s disease infection/expression as well.
• How MAP may cause disease in Crohn’s sufferers.

So how does MAP cause disease? How does this enigmatic bacterium kill certain immune cells and cause severe inflammation?

I’m proposing MAP is acidogenic! I’m proposing MAP causes disease by penetrating a potential host’s intestinal mucosal layer, attaching itself to the intestinal lining and, if a colony or colonies of MAP eventually become large enough, fermenting a wide-range of sugars (inc. starch or partially digested starch) to produce enough organic acid(s) at such a low ph to burn its host’s gut lining leading to various levels of inflamed tissues. The inflamed tissues then produce macrophage-colony stimulating factor (M-CSF) which cause macrophages to migrate to the site of inflammation where MAP invades them, replicates inside them and inevitably kills them, and a complex immune-system response follows possibly involving CD4+ T cells, IL-16, IL-18, etc. Over a period of time, with significant carbohydrate consumption, MAP colonies increase in size leading to greater levels of inflammation and, potentially, gross lesions and multiple ulcerations.

Furthermore, I’m proposing that gross lesions and ulcerations observed in MAP-infected CD patients and JD-inflicted animals are caused by an accumulation of microscopic intestinal-tissue burns, and, their immune systems try to prevent gut ulceration by thickening their intestinal walls.

Indeed, a Crohn’s study by Lee, DeSchryver-Kecskemeti and Stenson, noted “a statistically significant thickening of the muscularis mucosae when compared with disease controls”, and “similar findings were also present in a previously characterized experimental model of CD (trinitrobenzene sulfonic acid-induced colitis in rats), particularly in what appeared to be grossly strictured areas”. In addition, a study by Graham and colleagues noted an accumulation of collagen in the strictured intestines of Crohn’s patients. This was also observed by Patterson et al in cattle with Johne’s disease. Likewise, collagen accumulation was also found during an experimental study involving esophageal burns in rats.

I’m proposing that the source of sugars/starches, fermented by MAP to produce acid in JD-inflicted ruminants, is manufactured cattle feed - which is typically 65% carbohydrates. Indeed, Newman Turner, a cattle farmer from the UK, documented in his book, Fertility Farming (1951, Faber & Faber, London), that he believed “the widespread incidence of Johne’s disease coincided with the general use of manufactured cattle foods”. And, some farmers have observed cattle with clinical JD still seem to feed ‘well’ or even excessively.

(Source: http://www.crohns.org/map_food/photo.htm)

If carefully considered, a startling insight arises from my hypothesis: if it’s proven that MAP causes disease via acid production, like Streptococcus mutans the major cause of dental disease, it almost certainly proves MAP is a major cause Crohn’s! In other words, the first scientists to demonstrate that MAP causes disease by microscopically burning its hosts’ intestinal tissues, are also the first scientists to provide near overwhelming evidence that MAP is a major of Crohn’s disease! Read on…

As mentioned, I’m proposing MAP causes intestinal disease by producing acids that microscopically burn its host’s gut lining. So:

• Does MAP counter the antibacterial compounds of and kill macrophages by organic acid production? (In the same way I’m proposing it causes disease.)
• Does MAP almost exclusively express clinical disease in domestic ruminants because of the rich supply of carbohydrates in manufactured cattle feed? (Which are generally unavailable to wild animals and wildlife.)

• Did dietary calcium reduce the level of MAP infection in Beige mice by neutralizing some of the acids produced by MAP and therefore limited infection and disease expression? A recent study by Chata et al, noted that calcium gluconate was effective for relief of severe pain in 7 cases of hydrofluoric acid burn; evidently, the calcium gluconate reduced the effects of the acid burns.
• Do alkaline soil-types retard JD expression by buffering acids produced in MAP-infected ruminants? Does applying lime (calcium oxide) to pastures, which is used in the water and sewage industry to reduce acidity, hinder MAP’s ability to cause intestinal disease by neutralizing some of its acid production?
• Does MAP cause Crohn’s disease, in the same way I’m proposing it causes JD, by fermenting a wide-range of sugars (inc. starch or partially digested starch) to produce enough organic acid(s) at such a low ph to burn its human host’s gut lining, leading to various levels of low-grade intestinal inflammation and, potentially, gut lesions and ulceration? Many studies have noted high sugar/carb consumption in CD sufferers. And a number of studies have noted disease improvement or even remission in CD patients on low-carb (sugar restricted) diets.

  Additionally, Lee et al, as mentioned above, observed significant thickening of the intestinal wall in CD patients during a study which he noted was similar to acid-induced colitis in a previous experimental model of Crohn’s in rats. This is further supported by collagen accumulation noted in CD, JD and an experimental study involving esophageal burns in rats.

If MAP needs a supply of carbohydrates to produce acid and cause disease, how can my hypothesis explain the small number of documented cases of clinical Johne’s disease in wildlife? A study by Daniels and colleagues observed that ruminants will try to avoid but inevitably consume feed contaminated by wildlife faeces. Consequently, they suggested that contaminated feed may be potential source of bacterial infection for livestock. Likewise, did the documented cases of wildlife with clinical JD develop the disease as a result of consuming partially digested, MAP-infected cattle feed from pastures where clinically-infected ruminants with diarrhoea were grazed?

Streptococcus mutans, the major cause of dental carries, also causes disease by producing acids. The genomes of MAP and Streptococcus mutans have been sequenced. A comparison of their genomes may reveal similar virulence genes. Indeed, Tizard and colleagues conducted a study to find genes specific to MAP, and they identified “a low G+C content genetic island” which they associated with “LPS or extracellular polysaccharide biosynthesis”. A number of genetic islands have been identified in Streptococcus mutans' UA159 genome, including some with a low G+C content.

Institution: Animal Nutrition and Health Department, Scottish Agricultural College, West Mains Road, Edinburgh EH9 3JG.

Summary:Livestock feed is susceptible to contamination from wildlife excreta during on farm storage. Pathogens associated with diseases such as paratuberculosis, salmonella and cryptosporidiosis are present in wild rodent and bird excreta.

Feed stores on four farms in the east of Scotland were monitored monthly over the winter of 1998/9 to quantify the levels of wildlife faecal contamination. A mean of 79.9 rodent (95% confidence interval: 37.5-165.9) and 24.9 (14.3-41.7) bird faeces were deposited per m2 of stored feed per month. It was estimated that individual cattle and sheep could encounter 1626 and 814 wildlife faeces over the winter. A model based on the numbers of infected faeces consumed per annum was used to estimate 'infectious probabilities' (Pinf) required to account for the reported prevalence of paratuberculosis, salmonella and cryptosporidiosis in sheep and cattle in the east of Scotland in 1998.

Based on empirical data for input variables [the number of faeces encountered (Fe), the number ingested (Fi) and the prevalence of infection in wildlife species (Ip)], Pinf estimates ranged from 1.6 x 10(-8) for cryptosporidiosis in sheep to 8.2 x 10(-8) for paratuberculosis in cattle. The model suggested that ingestion of feed contaminated by wildlife faeces could account for the prevalence of all three diseases. Wildlife faecal contamination of stored feed should be given serious consideration as a potential source of infection to livestock.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12825742&query_hl=10&itool=pubmed_docsum

Institution: Animal Nutrition and Health Department, Animal Biology Division, Scottish Agricultural College, West Mains Road, Edinburgh EH9 3JG, UK.

Summary: On farms where rats and mice are present, unprotected livestock feed may become contaminated with rodent faeces, thereby creating a possible source of infection for cattle and sheep. Livestock unable to avoid contaminated feed may choose to eat it entirely, reject it completely or attempt to reject faeces selectively while consuming some of the feed.

Two experiments were conducted to investigate which of these three responses were demonstrated by livestock. Ten cattle and ten sheep were presented individually with three repeats of ten feed treatments. Treatments were based on two feed types (meal and pelleted compound), with three levels of contamination (none, 'low' and 'high'), from one of two rodent species (rat and mouse).Avoidance behaviour was greater for feed contaminated with rat faeces compared to feed contaminated with mouse faeces.

At low levels of rat contamination there was evidence that livestock actively rejected faeces whilst consuming feed. At higher levels of contamination animals rejected faeces and feed. Livestock could not actively discriminate against mouse faeces and thus rejection of feed was used to avoid faeces ingestion. Despite rejection of contaminated feed and some discrimination against faeces, significant numbers of rodent faeces were ingested illustrating that livestock feeding behaviour cannot prevent ingestion of rodent faeces. Feed contaminated with rodent faeces therefore poses a significant risk of disease infection to livestock. Copyright 2001 Harcourt Publishers Ltd.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11681871&query_hl=12&itool=pubmed_docsum

Institution: Animal Nutrition and Health Department, Scottish Agricultural College, Edinburgh.

Summary: The reported incidence of Johne's disease has been increasing in the east of Scotland since 1993. A postal questionnaire survey was sent to 127 farms to identify potential risk factors for Johne's disease in relation to wildlife and farm management practices, and 86 returns were obtained.

Of 22 farms which had been assumed to be free of the disease, on the basis of information held by local veterinary centres, seven (32 per cent) reported cases of Johne's disease in the 1990s, indicating that the disease is under-reported. Logistic regression analyses showed that eight of 63 potentially explanatory variables were significant at the 5 per cent level in affecting the likelihood of farms reporting Johne's disease. Of these, large numbers of livestock and rabbits, and access of wildlife to feed stores were the clearest and most consistent risk factors associated with the disease.

The application of manure to grazing pasture, the type of water supply for the cattle and the numbers of crows were also related to the presence of Johne's disease but the nature of these relationships was less clear. Only 38 per cent of the farms reported taking any control measures to combat Johne's disease, but three of the control measures were relevant to risk factors identified as significant by the survey, namely maintaining a clean water supply, controlling rabbits and not spreading manure on to grazing pasture.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11871666&query_hl=12&itool=pubmed_docsum

I’m further proposing that abnormal intestinal motility found in IBS sufferers (constipation, alternating constipation/diarrhoea, or diarrhoea) is directly related to the level of low-grade inflammation - as the inflammation varies so may the predominant bowel symptom. Consider the graph below.

Where N is normal bowel movement, C is constipation, A is alternating between constipation and diarrhoea, and D is diarrhoea.

Also, consider the three points below:

• Two studies have noted bowel-symptom instability in IBS sufferers.
• A significant number of studies have noted worsening symptoms in IBS patients after various quantities of sugar consumption. And, equally, numerous studies have noted symptom improvement in IBS patients after following assorted sugar-restricted diets.
• Various studies have observed low-grade intestinal inflammation in IBS patients; especially in D-IBS patients. In particular, elevated intraepithelial lymphocytes (IEL), lamina propria lymphocytes, and increased numbers of enteroendocrine cells have been found.

So, in view of my hypothesis above, decreased sugar consumption should reduce the level of low-grade inflammation and therefore affect the predominant bowel symptom.

I’m proposing a study that would test whether a low-carb diet would normalize low-grade intestinal inflammation found in a group of diarrhoea-predominant IBS patients, and consequently shift the predominant bowel symptom from diarrhoea to constipation or even return to normal.

The study would analyse intestinal mucosal biopsies from a group of severe diarrhoea-predominant IBS patients for inflammatory cells and inflammatory mediators. The group would then be advised eat a low-carbohydrate diet for 6-weeks or until their predominant-bowel symptom shifted to constipation or normal. After that, intestinal mucosal biopsies would be taken again and analysed for inflammatory cells and inflammatory mediators.

A small group of controls should be used without any history of IBS or recurrent bowel problems.

If my hypothesis is correct most, if not all, D-IBS patients should observe a shift from diarrhoea as the predominant bowel symptom to constipation or normal bowel movement, and results from the analysis and comparison of mucosal biopsies for inflammatory cells and inflammatory mediators should differ from their previous results and be similar to controls.

A complementary study to verify the opposite of this would involve a group of C-IBS patients consuming a high carbohydrate diet for six-weeks or until their predominant bowel symptom shifted to diarrhoea.

At the end of the complementary study, if my hypothesis is correct, results from the analysis and comparison of their mucosal biopsies for inflammatory mediators and inflammatory cells should differ from their original results at the start of the study, and the patients’ predominant bowel symptom should have shifted from constipation to diarrhoea.

I’m proposing that MAP causes disease by penetrating the mucosal layer, attaching itself to a host's intestinal lining and, if a colony or colonies of MAP eventually become large enough, fermenting a wide-range of sugars to produce enough organic acid(s) at low ph to burn the gut lining, leading to various levels of low-grade intestinal inflammation and, potentially, intestinal lesions and ulceration.

To test this hypothesis a study could be conducted over a six-month period to observe the effect of dietary sugars on intestinal disease expression in MAP-infected Beige mice.

Mice should be randomly assigned one of perhaps 5 diets. The diets should vary in sugar composition from exceptionally low to very high. Sugars that could be used in the diets include: sucrose, fructose, lactose, and starch.

Additionally, administering antibiotics before MAP inoculation may facilitate intestinal MAP infection.

If my hypothesis is correct and MAP successfully infects the mice intestines, various levels of Johne’s disease should be observed in the mice on autopsy: from virtually no signs of intestinal disease (very low carb diet) to pathological lesions and ulceration (very high carb diet).

(During this study, starch should be considered a fermentable sugar. Also, dried vegetables may contain a greater amount of starch than fresh vegetables; this may be an important factor when devising an exceptionally low-sugar diet.)

If MAP is a major cause of CD and IBS, does killing significant quantities of intestinal bacterial make it easier for MAP to get a ‘foothold’ in the intestines of a potential human host? It’s been noted that Crohn’s development may follow antibiotic use. And it’s also been noted that IBS development may also follow antibiotic use.

A study by Donaghy JA and colleagues, found that specific probiotic strains (Lb. paracasei isolates) inhibited MAP growth in milk. And several studies have noted disease/symptom improvement in CD/IBS sufferers taking probiotic supplements.

If specific bacteria have the ability to inhibit MAP growth, they may also hinder MAP's ability to initially infect a potential host.

Therefore, studies involving experimental MAP-infection may be more successful at inducing intestinal disease by first wiping out most of a potential host’s intestinal bacteria, via multiple courses of broad-spectrum antibiotics, before MAP inoculation.

Institution: Department of Surgery, St George's Hospital Medical School, London, UK.

Summary: Twenty patients with active Crohn's disease, the majority refractory to conventional therapy, were treated with rifampicin, ethambutol, isoniazid, and pyrazinamide or clofazamine for 9 months. After this period, 10 were in remission (Crohn's disease activity index less than 150).

Of the 10 not in remission, three had been at 6 months, but had relapsed on treatment. Nine of 10 patients on steroids at the beginning were off steroids at 9 months. Six patients came to surgery during the period, five for stricture formation without evidence of florid Crohn's disease outside the strictured segment. Three young patients with severe Crohn's disease facing total colectomy were spared surgery. No serious drug-related side-effects were encountered.

The results of this pilot study suggest that controlled trials of antimycobacterial chemotherapy, using four or more of the best agents available, are worthy of assessment in Crohn's disease.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2518848&query_hl=56&itool=pubmed_docsum

Institution: University Department of Surgery, St George's Hospital Medical School, London, UK.

Summary:Fifty-two patients with severe Crohn's disease were enrolled in this study. Six (11.5%) were intolerant of the medication and had to be excluded. The remaining 46 patients were treated with rifabutin in combination with a macrolide antibiotic (clarithromycin or azithromycin).

Patients were treated for a mean of 18.7 (range 6-35) months and followed up for 25.1 (range 7-41) months. Of the 19 patients who were steroid dependent at the start of this study, only two continued to require steroids when treatment was established. A reduction in the Harvey-Bradshaw Crohn's disease activity index occurred after 6 months' treatment (P = 0.004, paired Wilcoxon test) and was maintained at 24 months (P < 0.001).

An improvement in inflammatory parameters was observed as measured by a reduction in erythrocyte sedimentation rate (P = 0.009) and C-reactive protein (P = 0.03) at 18 months compared with pretreatment levels, and an increase in serum albumin at 12 months (P = 0.04). When subsets of the study population were analysed, patients with pan-intestinal disease achieved better remission at 2 years than did those with less extensive involvement (P = 0.04, Mann-Whitney U-test).

No difference in treatment response by age, disease duration, the presence of granulomas on histology, or the occurrence of drug-induced side-effects, was observed. These data suggest that treatment with rifabutin and clarithromycin or azithromycin may result in a substantial clinical improvement in Crohn's disease and justify the conduct of a randomized controlled trial.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9096189&query_hl=53&itool=pubmed_docsum

Institution: Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, USA. ira@shafran.net

Background: Crohn's disease, an inflammatory bowel disease in humans, has a suspected aetiology of Mycobacterium avium subsp. Paratuberculosis.

Results: Seven patients (19.4%) withdrew from the study since they were unable to tolerate medications. Of the remaining 29 patients, 21 (58.3%) reached a sustained state of improvement, traditionally defined as a decrease of 70 points between their entrance and exit Crohn's disease activity index scores together with the absence of the need of all other Crohn's medications, such as immunosuppressants and corticosteroids. Three Crohn's disease patients [8. 3%) noticed significant improvements, but required other Crohn's medications, concurrently with rifabutin and macrolide antibiotic therapy, to achieve and sustain improvement. Only 5 Crohn's disease patients (13.8%) were non-responders, noticing no marked improvement while on rifabutin and macrolide antibiotic therapy.

Conclusion: The data add further evidence to support the role of rifabutin and macrolide antibiotic therapy in the treatment of Crohn's disease specifically in those patients with evidence of Mycobacterium avium subsp. Paratuberculosis infection. A large multi-centre clinical trial is needed to further explore these findings.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11930899&query_hl=51&itool=pubmed_docsum

Institution: Klinikum Leverkusen, Medizinische Klinik 2, Germany.

Summary: Involvement of pathogenic or potentially pathogenic bacteria in the pathogenesis of inflammatory bowel disease has long been suggested because, among other reasons, the inflammatory response resembles that in infectious bowel diseases.

Elevated antibody levels to pathogen antigens and a changed metabolic activity of the intestinal microflora have been detected in patients with Crohn's disease. Several studies have revealed a possible etiologic link between intestinal microorganisms and inflammatory bowel disease…

Promising results came from the present pilot study in which the nonpathogenic Escherichia coli strain Nissle 1917 was tested for efficacy and tolerance in maintaining remission in patients with colonic Crohn's disease. Application of the physiologic bacteria reduced the risk for relapse and minimized the need for glucocorticoids. Therefore we are convinced that in Crohn's disease parts of the intestinal microflora, including the host's immune response toward indigenous flora or an impairment of the gut flora's metabolic activity are involved in the development or at least in the onset of relapse from remissive of colonic Crohn's disease.

However, more data are necessary to prove the benefit of E. coli strain Nissle 1917 as a new therapy to maintain remission of colonic Crohn's disease.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9451682&query_hl=47&itool=pubmed_docsum

Institution: Section of Pediatric Gastroenterology, Hepatology and Nutrition, The University of Chicago Children's Hospital, Illinois 60637, USA.

Background: Lactobacillus GG is a safe probiotic bacterium known to transiently colonize the human intestine. It has been found to be useful in treatment of several gastrointestinal conditions characterized by increased gut permeability. In the current study, the efficacy of Lactobacillus GG was investigated in children with Crohn's disease.

Conclusions: Findings in this pilot study show that Lactobacillus GG may improve gut barrier function and clinical status in children with mildly to moderately active, stable Crohn's disease. Randomized, double-blind, placebo-controlled trials are warranted for a final assessment of the efficacy of Lactobacillus GG in Crohn's disease.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11045848&query_hl=25&itool=pubmed_docsum

If MAP is a major cause of IBS, why would probiotics improve symptoms? A study by Donaghy JA and colleagues, found that specific probiotic strains (Lb. paracasei isolates) inhibited MAP growth in milk, and they concluded that the possibility exists for “their use as biotherapeutic agents in the gastro-intestinal tract”.

I’m proposing that MAP causes disease by attaching itself to a host's gut lining and fermenting a wide-range of sugars to produce enough organic acid(s) at low ph to burn the gut lining. Indeed, a significant number of studies have noted worsening IBS symptoms with various quantities of sugar consumption. And, conversely, a number of studies have noted symptom improvement on sugar restricted diets. Also, patient sugar consumption may explain why some probiotic studies failed to note symptom improvement.

If MAP causes IBS and MAP’s disease-causing is mechanism is acid production, combining a clinically-effective probiotic formula with a low-carb diet may be the most effective way to treat irritable bowel syndrome. A future study could test such a dietary/probiotic regimen.

Institution: Agriculture, Food and Environmental Science Division (Food Microbiology Branch), 1Dept. of Agriculture and Rural Development for N. Ireland; 2Dept. of Food Science, Queens University Belfast, Newforge Lane, Belfast, BT9 5PX, N. Ireland, United Kingdom

Summary: Dairy products such as cheese and yogurt are manufactured from pasteurised milk while in some cases sub-pasteurisation temperatures are employed for the former. Recent studies have shown increased survival of Mycobacterium avium subsp. paratuberculosis (Map) under such conditions. Therefore, the inactivation of this bacterium may rely on the manufacturing process or the product's intrinsic properties. Lactic acid bacteria (LAB) are known for their potential as inhibitors of food pathogens, a property exploited in their commercialisation as 'probiotic' products…

Map growth was inhibited (delayed) when supplemented with supernatants from a number of Lb. paracasei isolates. When co-inoculated with probiotic strains in sterile milk for 48 h (pH < 4.5) Map could not be detected by radiometric culture up to 50 days.The results of this study suggest the in vitro inhibitory effect of some lactobacilli on Map growth may be due to factors other than acid production. Irrespective of the mechanism of inhibition, the possibility exists for the inclusion of such strains in dairy products for the in situ inhibition of Map or furthermore their use as biotherapeutic agents in the gastro-intestinal tract.

Study link: http://www.paratuberculosis.org/proc8/abst4_p98.htm

Institution: Department of Pediatrics, University of Ottawa, and Children's Hospital of Eastern Ontario, Ottawa, Canada. dmack@cheo.on.ca

Purpose of Review: Using microorganisms to influence positively the course of an illness caused by injurious microorganisms is an approach with mounting clinical evidence showing efficacy. Whereas antibiotics will remain an important therapeutic option, there are limitations and problems to their increasing and chronic usage, and probiotics offer a strategy to reduce antibiotic usage. Increasingly, it has become clear that the mechanisms whereby probiotics can impact in intestinal diseases involve a large repertoire of responses. This review summarizes recent findings on how probiotics may effect benefit through interactions with host eukaryotic cells.

Recent Findings: Limiting the access of microbes associated with the development of disease to host mucosal surfaces and altering the responses of host to microbial insults are potential mechanisms whereby probiotics can influence the pathogenesis of disease. Evidence is accumulating that live, viable probiotic organisms diminish accessibility to intestinal epithelial cell; however, the mucosal exclusion is not through direct blockage of shared epithelial receptors between probiotic microbes and pathogenic organisms. Modulation of mucosal defenses such as innate protective mechanisms, enhanced epithelial cell survival, and immune responses have all been shown to have potential in aiding in these actions. Intestinal epithelial cell adherence influences response and, as such, appears to be necessary but may not be wholly sufficient, because soluble bacterial factors have been reported to effect modulation of immune and nonimmune responses of eukaryotic cells.

Summary: There is a considerable repertoire of responses potentially responsible for the effects of probiotics, and these responses appear to involve a complex interplay between the microbes of the intestinal tract and the cells of the host. Continued work can be expected to further the understanding of the mechanisms involved, and more work is needed to determine the relative clinical importance of each of the phenomena. These studies are expected to help direct the most efficacious use of probiotics for inflammatory conditions arising from the intestinal tract.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15703616&query_hl=14&itool=pubmed_docsum