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Microbiota intestinal, metabólitos fecais e biomarcadores salivares em crianças com tea: impactos da terapia multiprofissional sobre o eixo intestino–cérebro

2026-07-08T11:56:27Z

Título: Microbiota intestinal, metabólitos fecais e biomarcadores salivares em crianças com tea: impactos da terapia multiprofissional sobre o eixo intestino–cérebro Autor(es): Cristino, Larissa Maria Frota Abstract: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and restricted, repetitive patterns of behavior. Growing evidence suggests that alterations in the gut microbiota may contribute to its pathophysiology. This study aimed to characterize the gut microbiota of children with ASD and investigate its association with clinical, behavioral, and gestational factors, considering the duration of multidisciplinary therapeutic intervention. This was an observational, cross-sectional, case-control study including children aged 3 to 12 years with and without ASD. The study included 46 children with ASD recruited from the Early Treatment and Stimulation Center of the Federal University of Ceará (Núcleo de Tratamento e Estimulação Precoce – UFC) and 16 neurotypical children. Sociodemographic, gestational, and clinical data were collected using a structured questionnaire, and adaptive behavior was assessed using the Vineland-3. Gut microbiota composition was determined by 16S rRNA gene sequencing (Illumina NextSeq). Fecal metabolites and salivary biomarkers were quantified using HPLC, LC-MS/MS, ELISA, and SIMOA. Among children with ASD, 80.43% were male, 50% presented associated comorbidities, 62.86% had been exposed to gestational stress (p=0.0059), and 42.22% required neonatal hospitalization (p=0.0115). The ASD group showed lower scores across all Vineland-3 domains (p<0.0001). Gut microbiota analysis revealed significant differences in beta diversity between groups (PERMANOVA p=0.002; ANOSIM p=0.001), reduced alpha diversity in the ASD group (Observed richness p=0.024; Chao1 p=0.027; 1/Simpson index p=0.044), and an increased Firmicutes/Bacteroidota ratio (p=0.01). Differential abundance analysis identified enrichment of taxa belonging to the phyla Bacteroidota and Fusobacteriota in the control group, including the genera Bacteroides, Parabacteroides, and Fusobacterium, whereas the ASD group showed enrichment of taxa belonging to the phyla Actinomycetota and Pseudomonadota, particularly the genus Blautia, the family Eggerthellaceae, and the class Gammaproteobacteria. Children with a shorter duration of therapeutic intervention exhibited lower microbial richness and diversity, whereas those with prolonged intervention displayed microbial diversity profiles similar to those of the control group. Metabolic profiling revealed increased GABA (p=0.0041) and tryptophan (p=0.0146) levels in the ASD group. Children with shorter therapeutic intervention showed higher tryptophan levels (p=0.0271), whereas GABA (p=0.0298) and glutamate (p=0.0383) were associated with poorer Communication scores, and GABA (p=0.0309) and serotonin (p=0.0445) were associated with lower Adaptive Behavior Composite (ABC) scores. Children with ASD also exhibited reduced cortisol levels (p=0.0039) and an increased Aβ42/Aβ40 ratio (p=0.0461), suggesting hypothalamic-pituitary adrenal (HPA) axis dysfunction and possible neuroinflammation. Furthermore, the association between longer multidisciplinary therapeutic intervention and microbial diversity profiles similar to those observed in the control group reinforces the potential of the gut microbiota as a target for future therapeutic strategies in ASD Tipo: Tese

Nanoplásticos de poliestireno como moduladores do eixo microbiota-intestino-cérebro: implicações na disbiose e no estresse oxidativo em camundongas em diferentes fases do desenvolvimento

2026-05-20T12:30:13Z

Título: Nanoplásticos de poliestireno como moduladores do eixo microbiota-intestino-cérebro: implicações na disbiose e no estresse oxidativo em camundongas em diferentes fases do desenvolvimento Autor(es): Lima, Júlia Grombone de Vasconcellos Abstract: The environmental dissemination of micro- and nanoplastics (MNPs) has raised growing concerns regarding their impact on human health and the integrity of the microbiota-gut-brain axis. This study evaluated the effects of repeated oral exposure to polystyrene nanoplastics (100 nm, 40 mg/kg) over 21 days in late young (n=16) and pre-pubertal (n=15) female Swiss mice. Two cohorts underwent a battery of behavioral tests, including the Open Field Test and Forced Swim Test. Following euthanasia, fecal samples were collected for microbiota analysis via qPCR, and brain tissues—specifically the hippocampus (HP), prefrontal cortex (PFC), and striatum (STR)—were harvested to quantify biomarkers of oxidative and nitrosative stress. The results demonstrated that while there were no alterations in global locomotion or classical anxiety- and depression-like behaviors, exposed pre-pubertal animals showed a significant increase in peripheral rearing ($p=0.0252$) and grooming ($p<0.05$), indicating an age-dependent selective modulation of exploratory and emotional behavior. Regarding the gut microbiota, no changes were detected in the isolated abundances of Firmicutes or Bacteroidetes; however, a reduction in the Firmicutes/Bacteroidetes ratio was observed in both exposed groups ($p=0.0101$), suggesting the presence of subtle dysbiosis. Distinct vulnerabilities to nitrosative stress were observed according to the life stage: pre-pubertal animals exhibited a robust increase in nitrite levels (p=0.0017), whereas late youngs displayed a compensatory increase in reduced glutathione (GSH) (p=0.0136) within the hippocampus. In conclusion, repeated exposure to nanoplastics promotes low magnitude yet selective effects, with greater neurobehavioral and nitrosative vulnerability during the pre-pubertal stage. These findings provide evidence supporting the involvement of the microbiota-gut-brain axis in the toxicity of these emerging pollutants. Tipo: Dissertação

Avaliação da atividade antimicrobiana da hidralazina frente a Staphylococcus aureus e Candida spp

2026-05-18T13:13:30Z

Título: Avaliação da atividade antimicrobiana da hidralazina frente a Staphylococcus aureus e Candida spp Autor(es): Nascimento, Francisca Bruna Stefany Aires do Abstract: It is estimated that infectious diseases are the leading cause of death worldwide, responsible for approximately 13 million deaths each year. Staphylococcus aureus and Candida spp are among the main human pathogens, related to several infections with different levels of severity. Available treatments are increasingly limited. S. aureus has several virulence factors, in addition to easily acquiring resistance mechanisms. While Candida spp. mainly affects immunocompromised patients, has a small available pharmacological treatment arsenal and is affected by the toxicity fact. The new antimicrobials development is a global urgency and drugs repurposing is the fastest, most economical and safest mechanism. This study aimed to evaluate the antimicrobial activity of hydralazine, in vitro, against clinical strains of S. aureus and Candida spp biofilms, and to evaluate, in silico, the possible action mechanism. By microdilution in broth, the hydralazine minimum inhibitory concentration was determined, which was on average 256 µg/ml against S. aureus. In the tolerance assessment, hydralazine proved to be bactericidal and the association with oxacillin and vancomycin was synergistic in 50 and 25% of the strains, respectively. In evaluating the cell viability of biofilms formed by S. aureus by reducing Methylthiazolyldiphenyltetrazolium bromide (MTT), the sessile minimum inhibitory concentration (50%) ranged from 256 to 2048 µg/ml. Analysis of cell viability by propidium iodide exclusion showed that hydralazine increased non-viable cells (58.78%). In the Comet and TUNEL assays, it was possible to detect breaks and the fragmentation presence in the S. aureus DNA strands. In silico, hydralazine demonstrated greater affinity and the possibility of forming lower energy complexes with the targets S. aureus gyrase complex with DNA (-7.6 kcal/mol), S. aureus gyrase (-7.3 kcal/mol) and S. aureus TyrRS (-7.5 kcal/mol). Biofilms of Candida albicans, C. parapsilosis and C. tropicalis were treated with hydralazine, itraconazole and a combination of these drugs. Reduction in cell viability was assessed by MTT metabolization. Hydralazine (10xMIC) significantly (p≤0.05) reduced the biofilms formed viability. The biofilm formation inhibition was more effective and the MIC of hydralazine for each strain was able to significantly (p≤0.05) reduce biofilm viability. In scanning electron microscopy images, it is possible to see Candida albicans cells damaged by hydralazine. In in silico assays, hydralazine demonstrates more favorable binding energy with targets Exo-B-(1,3)-glucanase (-7.1 kcal/mol) and CYP51 (-7.2 kcal/mol). Therefore, it is concluded that hydralazine has potential to be redirected to the treatment of infections caused by S. aureus and Candida spp., in association with current drugs or alone, acting on planktonic cells and also on biofilms. Tipo: Tese

Investigação do papel das nets (armadilhas extracelulares de neutrófilos) na imunopatogênese da chikungunya

2026-04-30T12:17:27Z

Título: Investigação do papel das nets (armadilhas extracelulares de neutrófilos) na imunopatogênese da chikungunya Autor(es): Leal, Alberto Rubens Siqueira Nogueira Abstract: Neutrophil extracellular traps (NETs) are web-like structures composed of DNA, histones, and antimicrobial proteins released by neutrophils as part of the innate immune response. Although NETs have been extensively studied in bacterial infections, their role in viral diseases, such as Chikungunya virus (CHIKV) infection, remains poorly understood. In viral infections, NETs have an ambiguous role, being able to act as a defense mechanism, but can intensify inflammation and cause tissue damage when released excessively. CHIKV infection causes symptoms such as fever, malaise, rash, myalgia, and especially prolonged arthralgia, which can compromise quality of life. Although it is usually self-limiting, it can lead to death in at-risk groups, such as infants, the elderly, and people with comorbidities. The scarcity of studies on the role of NETs in CHIKV infection compromises the understanding of host defense mechanisms and limits the advancement of more effective therapeutic and diagnostic strategies. This study investigated the presence of NET markers during CHIKV infection over time in female patients. The study included 40 women with CHIKV infection, evaluated on days D0, D21, D90, D180 and D360, and the control group consisted of 10 healthy women. Tipo: Dissertação