Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system caused by myelin-specific autoreactive T cells. We previously demonstrated intestinal barrier disruption and signs of inflammation in experimental autoimmune encephalomyelitis (EAE), a model of MS. Fecal calprotectin is a disease activity biomarker in inflammatory bowel diseases, released by neutrophils in response to inflammation. We aimed to further investigate EAE manifestations in the gastrointestinal tract, and to determine whether calprotectin is a useful biomarker of intestinal inflammation in EAE. Calprotectin was analyzed in feces, cecal contents, and plasma of EAE mice. Infiltrating neutrophils and goblet cells were investigated in different parts of the gastrointestinal tract, before onset of neurological symptoms and during established disease. We found increased calprotectin levels in feces, cecal content and plasma, preceding EAE onset that further escalated during disease progression. Increased neutrophil infiltration in the intestinal tissue concomitant with IL-17 expression and myeloperoxidase activity was found correlating well with clinical activity. Increased goblet cells in intestine similar to irritable bowel syndrome (IBS) were also observed. The results suggest calprotectin as a good biomarker of gastrointestinal inflammation in EAE, also the potential of this model as a useful animal model for IBS.

(1) Background: Little research is done on the link of diabetic kidney disease (DKD) progression and diabetic gastroenteropathy in type 1 diabetes (T1D). (2) Methods. We performed a cross-sectional study with 100 T1D patients, 27 of them had progressive DKD, defined as estimated glomerular filtration rate (eGFR) decline≥3 ml/min/year or increased albuminuria stage over the mean follow-up time of 5.89±1.73 years. Newly developed score with 17 questions on gastrointestinal (GI) symptoms was used. Faecal calprotectin was measured by ELISA. Lower GI endoscopies were performed in 21 patients. (3) Results: Gastrointestinal symptom score demonstrated high reliability (Cronbach's α=0.78). Patients with progressive DKD had higher GI symptom scores compared to those with stable DKD (p=0.019). The former group demonstrated more frequent bowel movement disorders (p=0.04). The scores correlated negatively with eGFR (r = -0.335; p = 0.001), positively with albuminuria (r=0.245; p=0.015), Hba1c (r=0.305, p=0.002), diabetes duration (r=0.251, p=0.012). Faecal calprotectin levels did not differ between DKD groups significantly. The most commonly reported histopathological findings of enteric mucosa were infiltration with eosinophils, lymphocytes, plasmacytes, presence of lymphoid follicles and lymphoid aggregates. Conclusion: progression of DKD positively correlated with gastrointestinal symptoms, but more research is needed to clarify the causal relationships of the gut-kidney axis in T1D.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful in discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NET), calprotectin, DNase plasma levels by ELISA, and a panel of pro-inflammatory cytokines by ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and more in hospitalized than non-hospitalized ones. C5a and sC5b-9, and other acute phase proteins correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NET, and neopterin are important proinflammatory parameters potentially useful in discriminating between COVID-19 patients at risk for hospitalization.

Perinatal stress experienced by mothers of very premature newborns may influence the mother’s milk and the infant’s intestinal microbiota. This prospective study of mothers of very preterm infants fed with mother´s own milk (MOM) was carried out in a tertiary hospital over a 2-year period. Assessment of maternal stress in 45 mothers of 52 very preterm newborns using the parental stress scale (PSS:NICU) that revealed an inverse relationship between stress and MOM production in the first days of life (p=0.012). The greatest contributor to stress was the one related to the establishment of mother-child bond. Maternal stress was lower in mothers in whom the kangaroo method was established early (p=0.011) and in those with a higher educational level (p=0.032). Levels of fecal calprotectin (FC) decrease with the passage of days and were directly correlated with birthweight (p=0.044). FC levels 7 days post-delivery were lower in newborns that received postnatal antibiotics (p=0.027). High levels of maternal stress resulted in progressive decreases and increases in the proportions of Firmicutes and Proteobacteria species, respectively, over 15 days post-delivery, both in MOM and in fecal samples from premature newborns. These findings underscore the importance of recognizing and appropriately managing maternal stress in neonatal units, given its marked influence on both the microbiota of maternal milk and the intestinal microbiota of premature newborns.