The most prevalent diseases of our time, non-communicable diseases (NCDs) (including obesity, type 2 diabetes, cardiovascular diseases and some types of cancer) are rising worldwide. All of them share the condition of an “inflammatory disorder”, with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have in common malnutrition related to physiopathology. In this context, diet is the greatest modulator of immune system–microbiota crosstalk, and much interest, and new challenges, are arising in the area of precision nutrition as a way towards treatment and prevention. It is a fact that the westernized diet (WD) is partly responsible for the increased prevalence of NCDs, negatively affecting both gut microbiota and the immune system. Conversely, other nutritional approaches, such as Mediterranean diet (MD), positively influence immune system and gut microbiota, and is proposed not only as a potential tool in the clinical management of different disease conditions, but also for prevention and health promotion globally. Thus, the purpose of this review is to determine the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.

https://www.mdpi.com/2072-6643/13/2/699/pdf

Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota-Immune System Interplay. Implications for Health and Disease.

The single-cell thick intestinal epithelial cell (IEC) lining with its protective layer of mucus is the primary barrier protecting the organism from the harsh environment of the intestinal lumen. Today it is clear that the balancing act necessary to maintain intestinal homeostasis is dependent on the coordinated action of all cell types of the IEC, and that there are no passive bystanders to gut immunity solely acting as absorptive or regenerative cells: Mucin and antimicrobial peptides on the epithelial surface are continually being replenished by goblet and Paneth’s cells. Luminal antigens are being sensed by pattern recognition receptors on the enterocytes. The enteroendocrine cells sense the environment and coordinate the intestinal function by releasing neuropeptides acting both on IEC and inflammatory cells. All this while cells are continuously and rapidly being regenerated from a limited number of stem cells close to the intestinal crypt base. This review seeks to describe the cell types a...

Intestinal barrier homeostasis in inflammatory bowel disease.

Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells. Immunolabeling studies showed that the IL-6 receptor was restricted to the basal membrane of Paneth cells both in vitro and in vivo and that the crypt epithelium also expressed IL-6. Either a blocking Ab to the IL-6 receptor or a neutralizing Ab to IL-6 significantly reduced in vitro basal crypt organoid proliferation and budding, and in vivo significantly reduced the number of nuclei and the number of Lgr5EGFP-positive stem cells per crypt compared with IgG-treated mice, with the number of Paneth cells per crypt also significantly reduced. Functional studies demonstrated that IL-6-induced in vitro crypt organoid proliferation and crypt budding was abrogated by the Wnt inhibitor IWP2. This work demonstrates that autocrine IL-6 signaling in the gut epithelium regulates crypt homeostasis through the Paneth cells and the Wnt signaling pathway.

IL-6 Signaling Regulates Small Intestinal Crypt Homeostasis

Enteric defensins likely play a key role in the management of the human microbiome throughout development. The functional and mechanistic diversity of defensins is much greater than was initially thought. Defensin expression and overall Paneth cell physiology likely plays a key role in the development of colitis and other inflammatory or dysbiotic diseases of the gut. As our understanding of enteric defensins grows, their potential as tools of clinical intervention becomes more apparent. In this review, we focus on the function and activity of Paneth Cell defensins and highlight their role in disease.

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Guardians of the Gut: Enteric Defensins

Background Inflammatory bowel disease [IBD] results particularly from an aberrance of CD4+ helper and regulatory T cells and comprises histopathologically chronic active enterocolitis with features reflecting both activity and chronicity of mucosal inflammation. The exact immunological-histological correlation in IBD is not understood. Methods We studied the correlation between colonic mucosal CD4+ T cell subsets [Th1, Th2, Th17, Th22 and Treg] and mucosal histological changes in ulcerative colitis [UC] and Crohn's disease [CD]. CD4+ T cell subtyping and enumeration were achieved by flow cytometry. Histological features were categorized and assessed semi-quantitatively using three validated histological scoring schemes [ECAP, RHI and D'Haens]. Correlations between prevalence [%] of CD4+ T cell subsets and histological scores were analysed. Results Treg cells were correlated with ECAP category A [activity] as well as RHI scores. Treg cell were increased particularly in mucosa with severe neutrophilic infiltration in the cryptal/surface epithelium and in lamina propria, and with basal plasmacytosis. Th17 cells were also increased in cases with extensive neutrophil infiltrate in lamina propria, whereas RORc+ cells were increased in cases with severe lymphoplasmacytic infiltration in lamina propria. In both UC and CD, mucosa with marked crypt architectural alteration had increased IL-22+ and Th22 cells. UC with Paneth cell metaplasia had higher Th17 cells. CD with granuloma had increased IL-22+ and IL-22+IFN-γ+ cells. Conclusions The Treg subset appears to be associated with the overall severity of IBD histopathology, particularly with active inflammation. Th17 is also associated with activity. By contrast, IL-22+ cells are associated with chronicity and granuloma formation in CD.

/pdf/histopathological-features-of-inflammatory-bowel-disease-are-u7u5nquy2r.pdf

Histopathological Features of Inflammatory Bowel Disease are Associated With Different CD4+ T Cell Subsets in Colonic Mucosal Lamina Propria.

Paneth cell metaplasia (PCM) is well described in adults but little is known about the distribution of colonic Paneth cells and the occurrence of PCM in a paediatric population. The aim of this study is to determine whether Paneth cell hyperplasia or metaplasia characteristically occurs in the colons of children with newly diagnosed idiopathic inflammatory bowel disease (IBD). We retrospectively reviewed colonic series from 28 new diagnoses of paediatric IBD at a tertiary referral centre, and from a further 14 children with IBD-like symptoms whose colonic biopsies and ancillary investigations were normal. Paneth cells were counted at 6 anatomical sites in the colon, and at each site acute and chronic inflammation were assessed semi-quantitatively and the presence or absence of crypt architectural distortion and eosinophilia was documented. In control, ulcerative colitis (UC) and Crohn’s disease (CD) groups there was a gradient of decreasing Paneth cell numbers from caecum to rectum. Paneth cells were not seen in the distal colon in the control group, but they were present there in 11 of 13 patients with ulcerative colitis and 14 of 15 with Crohn’s disease. Only patients with IBD showed Paneth cell hyperplasia, assessed as more than 10 Paneth cells per 10 well-oriented crypts at any site. There was a statistically significant increase in Paneth cells in the caecum, ascending, transverse and descending colon in UC and in the ascending, transverse, descending and sigmoid colon in CD compared with controls. There was no significant difference between UC and CD. There was no correlation between the site of PCM and acute or chronic inflammation, crypt distortion or eosinophilia. Paneth cells are found in the proximal but not the distal colon in otherwise normal paediatric colonic series. A high proportion of UC and CD patients show PCM in the distal colon. This is present early in the disease and does not correlate with histological features of chronicity.

https://discovery.ucl.ac.uk/1432367/1/1471-230X-14-93.pdf

Evi Karanika

Papers

Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children.