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Abstract Background The gut microbiome has been reported to induce epigenetic modifications in the host, which may be involved in the pathophysiology of metabolic diseases. Objective To evaluate the potential interactions between the gut microbiome and DNA methylome in subjects with different metabolic characteristics. Methods Sixty-four participants with different metabolic characteristics (i.e., participants without obesity -healthy controls-, and participants with obesity and normal insulin sensitivity/insulin resistance/ type 2 diabetes-T2DM-) were included in this study. A machine learning approach was performed in order to identify distinctive patterns in three omics (gut microbiome, blood DNA methylome, and visceral adipose tissue-VAT- DNA methylome) according to the different study groups. Results Robust distinctive distribution patterns of the three different omics were found between healthy controls and patients with obesity; participants with and without T2DM, and patients with obesity with and without insulin resistance. Importantly, strong correlations between the gut microbiome (including Odoribacteriaceae and Christensenllaceae families) and both blood and VAT DNA methylome were found. Moreover, in the entire study population, three main bacterial genera (Sutterella, Collinsella and Eubacterium) were related to the epigenetic regulation of different genes involved in distinct processes related to cellular metabolism and metabolic diseases, including small ubiquitin-related modifier (SUMO) transferase activity or lipid binding. Conclusion We show that distinctive interactions between the gut microbiome and DNA methylome may occur in subjects with different metabolic characteristics. Further research is needed to elucidate the potential role of these interactions in the pathophysiology of obesity and related comorbidities.

Abstract Impulsivity is an important determinant of human behaviour, affecting self-control, reasonable thinking and food choices. Recent evidence suggests a role for gut microbiota in human behaviour, but the relationship between gut microbiota and impulsive behaviours remains largely unexplored. To address this knowledge gap, the present study aims to explore the associations between faecal microbiota composition with trait and behavioural impulsivity, in a subcohort of the PREDIMED-Plus trial, including older adults presenting overweight/obesity. Fecal samples (n = 231) were profiled for their microbiota composition using 16 S rRNA amplicon sequencing and impulsivity was determined through four different assessments. Adherence to different dietary patterns was estimated through questionnaires. Beta diversity analyses showed a significant association with the Conner’s Performance Test (CPT) in multivariate-adjusted models, and, in total, 13 bacterial genera associated with CPT. Erysipelotrichaceae UCG 003 showed the highest association with CPT and known butyrate producers such as Butyricicoccus spp., Roseburia spp., and Eubacterium hallii were among the identified bacteria. The bacteria Lachnospiraceae UCG 001, Anaerostipes and Blautia were associated with CPT and also the adherence to healthy and unhealthy plant-based diets. In addition, functional analysis showed a significant negative association between the CPT and the glucuronate and galacturonate metabolic pathways. From the other impulsivity assessments, two more associations were identified, for the genus Phascolarctobacterium with the Stroop test, and the genus Lachnospiraceae GAG 54 with the positive urgency subscore of UPPS-P Impulsive Behaviour Scale. Overall, our findings suggest potential links between the faecal microbiota composition and function with behavioural impulsive inattention as determined by the CPT.

IntroductionAxial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients.MethodsA cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay.ResultsR-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others.ConclusionAltogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.

West Nile virus (WNV) is a flavivirus naturally circulating between mosquito vectors and birds, occasionally infecting horses and humans and causing epidemiologically relevant outbreaks. In Spain, the first big WNV outbreak was recorded in 2020, resulting in 77 people infected and 8 fatalities, most of them in southern Spain. Culex perexiguus was identified as the primary vector of WNV maintaining its enzootic circulation of the virus. Growing evidence highlights the role of mosquito microbiota as a key component determining the vectorial capacity of mosquitoes, largely contributing to disease epidemiology. Here, we develop, to our knowledge, the first identification of the microbiota composition of this mosquito vector under natural conditions and test for the potential relationship between mosquito microbiota composition and WNV infection. To do so, we collected mosquitoes in a natural area of southern Spain during the 2020 WNV outbreak and identified the microbiota composition of mosquitoes using a 16S rRNA gene metabarcoding approach. The microbiota of Cx. perexiguus was dominated by the phylum Proteobacteria. The most abundant families were Burkholderiaceae and Erwiniaceae, including the genera Burkholderia, Erwinia, and Pantoea. The genus Wolbachia, which use to dominate the microbiota of Cx. pipiens and negatively interact with WNV according to the literature, had a low prevalence and relative abundance in Cx. perexiguus and its abundance did not differ between WNV-positive and WNV-negative mosquito pools. The microbiota diversity and composition of Cx. perexiguus were not significantly related to the WNV infection status. These results provide the first identification of the mosquito microbiota in an endemic area of WNV circulation in Spain.