An Update on the Role of Extracellular Vesicles in the Pathogenesis of Necrotizing Enterocolitis and Inflammatory Bowel Diseases

Some of the most fundamental influences of microorganisms inhabiting the human intestinal tract are exerted during infant development and impact the maturation of intestinal mucosa and gut immune system. The impact of bacteria on the host gut immune system is partially mediated via released extracellular vesicles (EVs). The heterogeneity in EV content, size, and bacterial species origin can have an impact on intestinal cells, resulting in inflammation and an immune response, or facilitate pathogen entry into the gut wall. In mammals, maintaining the integrity of the gut barrier might also be an evolutionary function of maternal milk EVs. Recently, the usage of EVs has been explored as a novel therapeutic approach in several pathological conditions, including necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). In this review, we attempt to summarize the current knowledge of EV biology, followed by a discussion of the role that EVs play in gut maturation and the pathogenesis of NEC and IBD.

Is Fecal Calprotectin an Applicable Biomarker of Gut Immune System Activation in Chronic Inflammatory Demyelinating Polyneuropathy? – A Pilot Study

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a complex autoimmune disease caused by dysregulated response to not fully recognized antigens. Some association between CIDP and inflammatory bowel disease (IBD) has been reported, but the exact pathophysiological links of these disorders are not well understood.Aim of the Study: To evaluate fecal calprotectin as a biomarker of gut inflammation in CIDP patients without IBD.Methods: Fifteen patients with CIDP and 15 healthy controls were included in the study. The CIDP diagnosis was based on the EFNS/PNS criteria. The occurrence of bowel symptoms was assessed based on a questionnaire. The quantitative evaluation of fecal calprotectin level was performed by the ELISA test.Results: The fecal calprotectin level (μg/g) expressed as median along with the lower and upper quartiles [25Q–75Q] was significantly higher in CIDP patients compared to the controls: 26.6 [17.5–109.0] vs 15.6 [7.1–24.1], p = 0.0066. Abnormal fecal calprotectin level (>50 μg/g) was found in 33% of all CIDP patients and in none of the control subjects. The patients with abnormal fecal calprotectin level did not differ from the rest of the study group regarding the neurological status. The most common bowel symptoms reported by CIDP patients included constipation (33%), feeling of incomplete evacuation (33%), bloating (27%), and alternating bowel movement pattern (27%).Conclusion: In one-third of CIDP patients the signs of gut immune system activation have been observed. This finding may be associated with CIDP pathogenesis and induction of autoimmune response as well as concomitant dysautonomia with gastrointestinal symptoms.

Microbiota regulates the turnover kinetics of gut macrophages in health and inflammation

The gut immune system has evolved to co-exist in a mutually beneficial symbiotic relationship with its microflora. Here, using a germ-free fate-mapping mouse model, we provide clear insight into how the enteric commensals determine the kinetics of macrophage turnover. The microbiome density along the gastrointestinal tract defines the persistence of ontogenically diverse macrophages, with the highest numbers of the long-lived F4/80hiTim4+ macrophage subset in the less densely colonized small intestine. Furthermore, the microbiome contributes to a tightly regulated monocyte-dependent replenishment of both long- and short-lived F4/80hi macrophages under homeostatic and inflammatory conditions. In the latter situation, the commensals regulate rapid replenishment of the depleted macrophage niche caused by the intestinal inflammation. The microbial ecosystem imprints a favorable cytokine microenvironment in the intestine to support macrophage survival and monocyte-dependent replenishment. Therefore, the host immune system-commensal cross-talk provides an efficient strategy to assure intestinal homeostasis.

Domestication and microbiome

In this paper we discuss two universal characteristics of domesticated species that distinguish them from the wild closely related ancestors – increased socialization and phenotypic variability. Examining evidence accumulated in the literature up to date, we note that the gut microbiome is involved in the increased social behavior of domesticated species through the gut-immune system-brain axis. We further discuss data that point toward clear difference in the microbiome composition between domesticated species and closely related wild ancestors. This difference is related to changes in diet, due to co-habitation with humans, which leads to increase in Bifidobacteria and changes in carbohydrate metabolism. We note that these changes may also influence interaction between microbiome and virome. Virome is linked to the evolutionary changes through incorporation of retro-viruses into the host genome. Together with transposons these mobile genetic elements may also lead to changes in regulatory networks, and increase adaptive potential. Changes in microbiome of animals during co-habitation with humans should be considered as an important event during domestication process.

Effect of fermented whey with a probiotic bacterium on gut immune system

The aim of the work presented in this Research Communication was to evaluate the effect of fermented whey (FW) with Lactobacillus rhamnosus RC007 in a mice model. BALB/c mice were divided into three groups: control group: animals received orally 0.1 ml of phosphate buffered saline (PBS); FW group: animals received orally 0.1 ml of FW; whey (W) group: animals received orally 0.1 ml of W without fermentation with probiotic bacterium. After 10 d mice were sacrificed. Small intestines were collected for determination of IL-10; IL-6, TNFα, goblet cells and intraepithelial lymphocytes. Increases of all the cytokines assayed were observed in mice that received FW compared to control and W group. The ratio between the anti and pro-inflammatory cytokines (IL-10/TNFα) increased in the group of mice that received FW. The number of goblet cells and intraepithelial lymphocytes were also increased in animals that received FW. The results showed that FW with L. rhamnosus RC007 was able to stimulate and to modulate mouse immune system. Whey fermented by this probiotic bacterium is an interesting alternative for development of a new food additive for pig production, taking advantage of the beneficial properties of probiotic bacterium and the nutritional properties of whey.

C-type lectin receptor-mediated immune recognition and response of the microbiota in the gut

C-type lectin receptors (CLRs) are powerful pattern-recognition receptors that discern ‘self’ and ‘non-self’ in our body and protect us from invasive pathogens by mediating immune recognition and response. The gastrointestinal tract is very important for the maintenance of homeostasis; it is the largest shelter for the billions of microorganisms in the body and CLRs play a crucial regulatory role in this system. This study focuses on several CLRs, including Dectin-1, Dectin-2, Dectin-3 and Mincle. We summarize the roles of CLRs in maintaining gastrointestinal immune-system homeostasis, especially their functions in mediating immune recognition and responses in the gut, discuss their relationships to some diseases, highlight the significance of CLR-mediated sensing of microbial and non-microbial compounds in the gut immune system and identify new therapeutic targets.