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Crohn’s, immunity and bacteria: who’s behind who?

Chron’s disease is a chronic inflammatory disease of the digestive system and can affect, with segmental distribution, any section from the mouth to the anus. As a rule the disease is the last section of the small intestine or the colon or the large intestine. The cause has not been definitively identified, but it is known that the immune system is the main orchestrator of the pathogenesis of Chron’s disease. In addition, its onset can be traced back to three interacting factors: (1) damage to intestinal mucous membranes due to an abnormal immune reaction depending on the intestinal flora (microbiota); which in turn (2) is rooted in a genetically determined susceptibility (in most cases there is a mutation of the NOD2 gene). Finally, various environmental factors (3) can contribute to the appearance, the most incriminated of which is smoking since it has been shown that it can alter the composition of the intestinal microbiota. Finally, if external circumstances allow it, severe emotional stress can cause an immune imbalance that, possibly, is reflected back into the microbiota itself. In every healthy subject, the intestinal mucosa is in a state of controlled inflammation; but the production of Immunoglobulin A (IgA) antibodies allows the elimination of microbes by the immune system. In Crohn’s disease, however, this mechanism is unregulated and destroys the mucosa.

The right composition of the intestinal microbiota controls the inflammation caused by wrong nutrition, voluntary risk factors, overlapping infections, etc. But if the combination of causative factors becomes optimal, the imbalance of the bacterial flora can activate the immune system in a deviated way, injuring the intestine. The first data on the altered composition of faecal microbiota in inflammatory bowel disease have since 2006, which was noted an excessive presence of Bacteroides and Escherichia and less presence of Clostridium species, in both adult and pediatric patients. In almost all cases, the count of a species called Faecalibacterium prausnitzii was also very low. On the contrary, on the other hand, there were no large variations of Gram-positive bacteria such as Lactobacillus, Bifidobacterium and Staphylococcus. This is probably the reason why the use of classical probiotics has never been encouraged, as a complement to drug therapy, to treat the disease. Furthermore, the results of clinical trials with these preparations have always been conflicting, as can be seen from the numerous reviews in the scientific literature. Indeed, in some studies the benefit of administering probiotics to patient cohorts appeared clear, in other cases it had almost no effect, in others it was fluctuating. Without going into the merits of the criteria with which these studies were conducted, it is important to underline that the types of patients may also differ by biological status.

That is, the composition of the intestinal microbiota of those suffering from Chron’s disease may differ according to its background, i.e. lifestyle, diet, genetic terrain, etc. In this case, the pathogenic composition of the microbiota may differ between the various cohorts of individuals. However, in those few published clinical trials, the protracted administration of classical probiotics improved both the immune and inflammatory response, in the laboratory animal and in patients (Karimi O et al., 2005; Lorea-Baroja M et al., 2007 ; Zakostelska Z et al., 2011; Shadnoush M et al., 2015; Thakur BK et al., 2016; Bailey JR et al., 2017; Plaza-Diaz J et al., 2017). This indicates that these bacterial species can still condition the intestinal environment, being able to benefit from the slowing down of the disease progression. Various scientific reviews agree on this point (see the extensive bibliography attached to the article) and suggest however the cyclic administration of probiotics in patients with Chron’s disease. It is not yet known with certainty whether these bacterial species can affect, and how, the species that have been altered in individuals with Chron’s disease. Some effect is certain, otherwise there would be no positive results in some contexts.

But it is probable that for the treatment of this pathology, there is a need to elaborate one or more supplements with selected probiotics. According to the orientation of the experts, it is encouraged to those suffering from Chron’s disease to support the intestinal bacterial flora, with the assumption of multi-strain probiotic formulations. On the contrary, those with only one strain should be avoided, since there is a risk of colonizing only one species of probiotic, to the detriment of other normal beneficial bacterial species. For completeness it is recommended to abolish cigarette smoking and to minimize the introduction of food antigens that could exacerbate the disease. This refers in particular to wheat gluten. Although no direct link between wheat proteins and the appearance of Chron’s disease is demonstrated, all experts agree to limit the introduction of starchy foods (bread, pasta, etc.), representing gluten as a strong external antigenic component. If the participation of the mycobioma is excluded, finally. In fact, unlike the microbiota, the mycobioma is the whole of the fungal communities that naturally lodge in the intestine. These are also altered in Chron’s disease and almost nothing is known about their intervention in the pathogenesis or progression of the disease. Moreover, it seems that most of the fungal strains residing in the gut do not correspond to the Candida or Saccharomyces genera, as previously believed. This means that if there is a micotic intervention in the disease, this could depend on strains not yet studied. There is evidence, however, that the treatment of Chron patients with antifungal medications (ketoconazole, nystatin) can make improvements in the symptoms in at least half of them.

All that remains is to wish good luck to the experts in the field.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical  Biochemistry.

Scientific literature

Ahmed I et al. Microorganisms. 2016 Jun 15; 4(2). Review

Bailey JR et al. Benef Microbes. 2017 Aug 24; 8(4):605-614. 

Derwa Y et al. Aliment Pharmacol Ther. 2017; 46(4):389-400.

Fujiya M et al. Clin J Gastroenterol. 2014 Feb; 7(1):1-13. 

Gong D et al. Gastroenterol Res Pract. 2016; 2016:6951091.

Hager CL, Ghannoum MA. Dig Liver Dis. 2017; 49(11):1171-76.

Korada SK et al. Curr Pharm Des. 2016; 22(7):904-17. Review.

Kosler S, et al. Curr Pharm Biotechnol. 2017; 18(4):318-326. 

Saez-Lara MJ et al. Biomed Res Int. 2015;2015:505878.

Shadnoush M et al. Korean J Gastroenterol. 2015; 65(4):215-21.

Thakur BK et al. Int Immunopharmacol. 2016 Jul; 36:39-50.

Vemuri R et al. Curr Pharm Des. 2017; 23(16):2352-2355.

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica e salute sui siti web salutesicilia.com, medicomunicare.it e in lingua inglese sul sito www.medicomunicare.com
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