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Cow's milk allergy (CMA) is one of the earliest and most common food allergy and can be elicited by both IgE- or non-IgE-mediated mechanism. We previously described dysbiosis in children with IgE-mediated CMA and the effect of dietary treatment with extensively hydrolyzed casein formula (EHCF) alone or in combination with the probiotic Lactobacillus rhamnosus GG (LGG). On the contrary, the gut microbiota in non-IgE-mediated CMA remains uncharacterized. In this study we evaluated gut microbiota composition and fecal butyrate levels in children affected by non-IgE-mediated CMA. We found a gut microbiota dysbiosis in non-IgE-mediated CMA, driven by an enrichment of Bacteroides and Alistipes. Comparing these results with those previously obtained in children with IgE-mediated CMA, we demonstrated overlapping signatures in the gut microbiota dysbiosis of non-IgE-mediated and IgE-mediated CMA children, characterized by a progressive increase in Bacteroides from healthy to IgE-mediated CMA patients. EHCF containg LGG was more strongly associated with an effect on dysbiosis and on butyrate production if compared to what observed in children treated with EHCF alone. If longitudinal cohort studies in children with CMA will confirm these results, gut microbiota dysbiosis could be a relevant target for innovative therapeutic strategies in children with non-IgE-mediated CMA.

Gut microbiota imbalances have a significant role in the pathogenesis of Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD). Herein, we compared gut microbial composition in patients diagnosed with either IBD or NAFLD or a combination of both. Seventy-four participants were stratified into four groups: IBD-NAFLD, IBD-only, NAFLD-only patients, and healthy controls (CTRLs). The 16S rRNA was sequenced by Next-Generation Sequencing. Bioinformatics and statistical analysis were performed. Bacterial α-diversity showed a significant lower value when the IBD-only group was compared to the other groups and particularly against the IBD-NAFLD group. β-diversity also showed a significant difference among groups. The higher Bacteroidetes/Firmicutes ratio was found only when comparing IBD groups and CTRLs. Comparing the IBD-only group with the IBD-NAFLD group, a decrease in differential abundance of Subdoligranulum, Parabacteroides, and Fusicatenibacter was found. Comparing the NAFLD-only with the IBD-NAFLD groups, there was a higher abundance of Alistipes, Odoribacter, Sutterella, and Lachnospira. An inverse relationship in the comparison between the IBD-only group and the other groups was shown. For the first time, the singularity of the gut microbial composition in IBD and NAFLD patients has been shown, implying a potential microbial signature mainly influenced by gut inflammation. [ABSTRACT FROM AUTHOR]

Objective: There are few comparative data on the third‐generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives. Methods: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add‐on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan–Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models. Results: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)‐naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17–3.29) and PER groups (HR = 1.64, 95% CI = 1.06–2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71–16.61), as well as PER‐treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05–2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] =.08, 95% CI =.01–.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV‐naïve (OR = 10.32, 95% CI = 1.55–68.78) versus men. PER (OR = 6.93, 95% CI = 3.32–14.44) and BRV in LEV‐naïve patients (OR = 6.80, 95% CI = 2.64–17.52) had a higher chance of AEs than LCM. Significance: Comparative evidence from real‐world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics. [ABSTRACT FROM AUTHOR]

Gut dysbiosis has been involved in the pathogenesis and progression of Parkinson's disease (PD), but the mechanisms through which gut microbiota (GM) exerts its influences deserve further study. Recently, we proposed a two-hit mouse model of PD in which ceftriaxone (CFX)-induced dysbiosis amplifies the neurodegenerative phenotype generated by striatal 6-hydroxydopamine (6-OHDA) injection in mice. Low GM diversity and the depletion of key gut colonizers and butyrate producers were the main signatures of GM alteration in this model. Here, we used the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) to unravel candidate pathways of cell-to-cell communication associated with dual-hit mice and potentially involved in PD progression. We focused our analysis on short-chain fatty acids (SCFAs) metabolism and quorum sensing (QS) signaling. Based on linear discriminant analysis, combined with the effect size results, we found increased functions linked to pyruvate utilization and a depletion of acetate and butyrate production in 6-OHDA+CFX mice. The specific arrangement of QS signaling as a possible result of the disrupted GM structure was also observed. With this exploratory study, we suggested a scenario in which SCFAs metabolism and QS signaling might represent the effectors of gut dysbiosis potentially involved in the designation of the functional outcomes that contribute to the exacerbation of the neurodegenerative phenotype in the dual-hit animal model of PD. [ABSTRACT FROM AUTHOR]

Glucagon exerts multiple hepatic actions, including stimulation of glycogenolysis/gluconeogenesis. The liver plays a crucial role in chronic inflammation by synthesizing proinflammatory molecules, which are thought to contribute to insulin resistance and hyperglycaemia. Whether glucagon affects hepatic expression of proinflammatory cytokines and acute‐phase reactants is unknown. Herein, we report a positive relationship between fasting glucagon levels and circulating interleukin (IL)‐1β (r = 0.252, p =.042), IL‐6 (r = 0.230, p =.026), fibrinogen (r = 0.193, p =.031), complement component 3 (r = 0.227, p =.024) and high sensitivity C‐reactive protein (r = 0.230, p =.012) in individuals without diabetes. In CD1 mice, 4‐week continuous treatment with glucagon induced a significant increase in circulating IL‐1β (p =.02), and IL‐6 (p =.001), which was countered by the contingent administration of the glucagon receptor antagonist, GRA‐II. Consistent with these results, we detected a significant increase in the hepatic activation of inflammatory pathways, such as expression of NLRP3 (p <.02), and the phosphorylation of nuclear factor kappaB (NF‐κB; p <.02) and STAT3 (p <.01). In HepG2 cells, we found that glucagon dose‐dependently stimulated the expression of IL‐1β (p <.002), IL‐6 (p <.002), fibrinogen (p <.01), complement component 3 (p <.01) and C‐reactive protein (p <.01), stimulated the activation of NLRP3 inflammasome (p <.01) and caspase‐1 (p <.05), induced the phosphorylation of TRAF2 (p <.01), NF‐κB (p <.01) and STAT3 (p <.01). Preincubating cells with GRA‐II inhibited the ability of glucagon to induce an inflammatory response. Using HepaRG cells, we confirmed the dose‐dependent ability of glucagon to stimulate the expression of NLRP3, the phosphorylation of NF‐κB and STAT3, in the absence of GRA‐II. These results suggest that glucagon has proinflammatory effects that may participate in the pathogenesis of hyperglycaemia and unfavourable cardiometabolic risk profile. [ABSTRACT FROM AUTHOR]