Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

Abstract

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota-heat shock proteins (HSPs)-probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota's composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extraintestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient's microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for 123Med Microbiol Immunol DOI 10.1007/s00430-013-0305-2 sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.

Streptozotocin-induced type-1-diabetes disease onset in Sprague–Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity

“…Indeed, the intestinal microbiota is an environmental factor that cannot be overlooked as a contributor towards T1D development or a factor that is significantly altered as a result of T1D development. Many studies have linked alterations in the intestinal microbiota composition with conditions such as obesity (Ley et al, , 2005Murphy et al, 2010;Turnbaugh et al, 2006), inflammatory bowel disease (Greenblum et al, 2012), colitis (Bellavia et al, 2013;Klimesova et al, 2013) and T1D Murri et al, 2013;Roesch et al, 2009). Moreover, risk of T1D onset in childhood is higher in children delivered by Caesarean section (Cardwell et al, 2008), where there is also altered microbiota composition (Dominguez-Bello et al, 2010).…”

Nutrition, oxidative stress and intestinal dysbiosis: Influence of diet on gut microbiota in inflammatory bowel diseases

“…Several studies have shown a correlation between increased oxidative stress and a Western-style diet rich in fats and refined sugars. These products in fact, if taken frequently and in large quantities, cause an increase of the inflammatory state with ROS production and subsequent amplification of the inflammatory cascade [21][22][23] . Currently, there are also discussions about the potential role of heat shock proteins (HSPs) in the pathogenesis of IBD.…”

“…HSPs are involved in various processes such as folding, translocation and degradation of intracellular proteins under normal and stressful conditions. Being highly conserved molecules with similar sequences in bacterial and human orthologs (molecular mimicry), HSPs can stimulate an immune response, both innate and adaptive and hence primary targets of the autoimmune response 5,21 . Furthermore, intestinal dysbiosis is often accompanied by a reduction in obligate anaerobic bacteria and an increase in facultative anaerobes.…”

The Modern View of the Pathogenesis and Laboratory Diagnostics of Ulcerative Colitis (Literature Review)

“…У лиц, стра-дающих ВЗК, изменяется соотношение нормальных и патогенных кишечных бактерий. При ЯК имеет значение изменение метаболизма или вирулентных свойств комменсальных бактерий [10,22,26 ].…”