Hypercaloric diets overactivate the intestinal immune system and disrupt the microbiome and epithelial cell functions, impairing glucose metabolism. The origins of this inflammatory cascade are poorly characterized. We investigated the involvement of intestinal proinflammatory group 1 innate lymphoid cells (ILC1s) in obesity progression and metabolic disruption. In obese mice, we studied longitudinally the ILC1s response to the diet and ILC1s depletion to address its role in obesity. ILC1s are required for the expansion of pro-inflammatory macrophages and ILC2s. ILC1s depletion induced the ILC3-IL-22 pathway, increasing mucin production, antimicrobial peptides, and neuroendocrine cells. These changes were translated into higher gut hormones and reduced insulinemia and adiposity. ILC1s depletion was also associated with a bloom in Akkermansia muciniphila and decreases in Bilophila spp. Intestinal-ILC1s are upstream activators of inflammatory signals, connecting immunity with the microbiome, the enteroendocrine system, and the intestinal barrier in the control of glucose metabolism and adiposity.

Minimal hepatic encephalopathy (MHE) is associated with changes in the immune system including an increased pro-inflammatory environment and altered differentiation of CD4+ T lymphocytes. The mechanisms remain unknown. Changes in extracellular vesicle (EV) cargo including proteins and miRNAs could play a main role as mediators of immune system changes associated with MHE. The aim was to assess whether plasma EVs from MHE patients played a role in inducing the pro-inflammatory environment and altered differentiation of CD4+ T lymphocyte subtypes in MHE patients. We characterized the miRNA and protein cargo of plasma EVs from 50 cirrhotic patients (27 without and 23 with MHE) and 24 controls. CD4+ T cells from the controls were cultured with plasma EVs from the three groups of study, and the cytokine release and differentiation to CD4+ T-cell subtypes were assessed. Plasma EVs from MHE patients had altered miRNA and protein contents, and were enriched in inflammatory factors compared to the controls and patients without MHE. EVs from MHE patients modulated the expression of pro-inflammatory IL-17, IL-21, and TNF-α and anti-inflammatory TGF-β in cultured CD4+ T lymphocytes, and increased the proportion of Th follicular and Treg cells and the activation of Th17 cells. In conclusion, plasma EVs could play an important role in the induction of immune changes observed in MHE.

Periodontal diseases are highly prevalent in dogs and intricately interconnected with the composition and functional attributes of the oral microbiota. The demand for non-invasive interventions to support oral health presents an opportunity for functional ingredients. The novel postbiotic heat-treated (HT) Lactiplantibacillus plantarum CECT 9161 inhibited growth and biofilm formation of oral microorganisms in vitro. The in vitro growth of saliva-derived biofilms was also inhibited and revealed microbiome modulation. Two doses of the postbiotic (LOW: 5 mg dog/day, HIGH: 25 mg/dog/day) were assessed in a placebo-controlled, double-blinded, 57-day clinical trial involving 60 dogs. Associations were found between the postbiotic, reduced plaque formation, and modulation of the oral microbiome, including increased abundance of genes involved in denitrification, heme and catechol biosynthesis, and oxidative stress reduction. The results suggest that HT Lactiplantibacillus plantarum CECT 9161 may support oral health in dogs by modifying the microbiome of supragingival plaque and reducing plaque formation.

B- and T-cell receptor (immune) repertoires can represent an individual’s immune history. While current repertoire analysis methods aim to discriminate between health and disease states, they are typically based on only a limited number of parameters (e.g., clonal diversity, germline usage). Here, we introduce immuneREF: a quantitative multi-dimensional measure of adaptive immune repertoire (and transcriptome) similarity that allows interpretation of immune repertoire variation by relying on both repertoire features and cross-referencing of simulated and experimental datasets. immuneREF is implemented in an R package and was validated based on detection sensitivity of immune repertoires with known similarities and dissimilarities. To quantify immune repertoire similarity landscapes across health and disease, we applied immuneREF to >2400 datasets from individuals with varying immune states (healthy, [autoimmune] disease and infection [Covid-19], immune cell population). Importantly we discovered, in contrast to the current paradigm, that blood-derived immune repertoires of healthy and diseased individuals are highly similar for certain immune states, suggesting that repertoire changes to immune perturbations are less pronounced than previously thought. In conclusion, immuneREF implements population-wide analysis of immune repertoire similarity and thus enables the study of the adaptive immune response across health and disease states.

This study evaluated the anti-inflammatory potential of gilthead seabream somatostatin-6 (SST6) in a λ-carrageenan-induced inflammation model using RNA-seq transcriptomics. We compared gene expression in the skin (primary site of sterile inflammation) and brain (main neuropeptide reservoir) to determine if peripheral signaling elicits coordinated local and central reprogramming, indicative of a neuroimmune axis during inflammation. The results showed that λ-carrageenan induced significant transcriptomic changes, particularly in the skin, while SST6 exerted a more substantial modulatory effect in the brain. Functional enrichment analysis revealed distinct pathway variations across conditions, with λ-carrageenan activating general metabolism, apoptosis, and proteasome degradation in the skin, while repressing innate immune response and neurogenesis. In the brain, λ-carrageenan activated NF-κB cascade, neurotransmitter release, and apoptotic mechanisms, while repressing neuronal development and PTEN regulation. SST6 treatment sustained the activation of adaptive immunity and neural pathways in the skin, while activating RNA-synthesis regulation, sensory-organ development, and neurotransmitter transport/release in the brain. The combined treatment (λ-carrageenan + SST6) showed a reversal of some λ-carrageenan-induced changes, particularly in the brain. This study provides novel insights into the anti-inflammatory action of a cortistatin functional analogue in teleosts, paving the way for strategies to bolster fish welfare and resilience under inflammatory challenges.