Protective effects of fecal microbiota transplantation in sepsis are independent of the modulation of the intestinal flora.

OBJECTIVE: The aim of this study was to investigate the protective effects of probiotics and fecal transplantation on inflammatory and oxidative parameters in the intestines of two rat models of sepsis. METHODS: Rats were treated with prebiotics, probiotics, or symbiotics and exposed to lipopolysaccharide (LPS) or zymosan after 15 d to induce endotoxemia. Oxidative damage and inflammation were analyzed, and histologic examination of the intestinal tissue was performed. Fecal microbiota transplantation (FMT) was carried out in LPS- and zymosan-induced rat models of sepsis. RESULTS: Supplementation with symbiotics for 15 d effectively reduced the inflammatory parameters compared with supplementation for 7 d. Probiotics, prebiotics, and symbiotics exerted different effects on the evaluated parameters. In general, Lactobacillus rhamnosus and L. casei exerted better local protective effects. Evaluation of the role of the intestinal microbiota through FMT revealed its protective effects irrespective of the previous treatment with probiotics. CONCLUSION: Probiotic strains significantly differ among themselves and exert different effects on the host's health. Symbiotics and FMT could offer additional immunomodulatory benefits to drug therapy, thus serving as a new therapeutic alternative in pediatric patients with sepsis.

The impact of age on long-term behavioral and neurochemical parameters in an animal model of severe sepsis.

This study aimed to evaluate behavioral and neurochemical parameters in adult (180-day-old) and young (60-day-old) rats subjected to sepsis. Sepsis was induced by cecal ligation and perforation (CLP). Thirty days after surgery, behavioral tests were performed, and the ß-amyloid content, oxidative damage, and cytokine levels were measured in the hippocampus and prefrontal cortex. In both adult and young rats, sepsis impaired the inhibitory avoidance task performance and increased immobility time in the forced swimming test. However, the adult septic rats had a higher immobility time compared to the young rats. Both sepsis and aging induced brain inflammation and oxidative damage and increased Aß content. Sepsis along with aging had additive effects on hippocampal interleukin-1 levels and prefrontal carbonyl levels. Taken together, our results suggest that age has a minor influence on brain inflammation and behavioral alterations observed in septic rats.

The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious disease that affects premature neonates, causing high mortality. In the search for new options of treatment it was investigated whether fecal microbiota transplantation (FMT) decreased the inflammatory response during NEC development in experimental model. METHODS: Wistar rats were used and divided as follows: naïve, control (NEC induction), FMT-before (transplantation of microbiota before insult) and FMT-after (microbiota transplantation after insult). The microbiota transplantation was performed by administering a feces solution obtained from an adult donor rat. The induction of enterocolitis involves feeding by artificial formula, hypothermia, hypoxia and endotoxin administration. MPO activity, TNF-α, IL-1ß and IL-6 levels, oxidative and nitrosative damage and the grade of intestinal mucosa lesion were analyzed. RESULTS: The control group had a significant increase of inflammatory and oxidative parameters when compared to naive animals. Both FMT-before and after decreased all inflammatory and oxidative damage parameters when compared to control group. This was also true to the intestinal mucosa damage. CONCLUSION: FMT administered just before or after NEC induction improved gut and systemic inflammation, and gut oxidative damage and intestinal injury.

Anxious phenotype potentiates damage in peripheral organs of animals submitted to sepsis / Fenótipo ansioso potencializa danos em órgãos periféricos de animais submetidos à sepse

Introduction: Anxiety and sepsis are important public health problems that present high morbidity, mortality and significant economic repercussions. The present study investigated the presence of oxidative damage in peripheral organs in two lines of animals that are bred for high and low freezing responses to contextual cues that are previously associated with foot shock (Carioca High-conditioned Freezing [CHF] and Carioca Low-conditioned Freezing [CLF]) associated to sepsis. Methods: Animals were subject to sepsis by the cecal ligation and perforation (CLP) or sham operated. 24 hours and 10 days after sepsis animals were euthanized and removed adrenal, kidney, lung, serum, heart for the determination of carbonyl protein levels and adrenal for check weight this structure. Results: Sepsis increased oxidative damage in different systemic organs, included serum. There wasn't a significant increase in protein carbonyls in heart and kidney. Anxious phenotype potentiates this damage. Conclusion: These findings suggest that an anxious phenotype plus sepsis may induce more pronounced organs damage, and promote more alterations in the HPA axis. These findings may help to explain, at least in part, the common point of the mechanisms involved with the pathophysiology of sepsis and anxiety.

Introdução: Ansiedade e sepse são importantes problemas de saúde pública que apresentam alta morbidade, mortalidade e repercussões econômicas significativas. O presente estudo investigou a presença de dano oxidativo em órgãos periféricos em duas linhagens de animais criados para respostas de alta (CHF) e baixa (CLF) ansiedade associado a sepse. Métodos: Os animais foram submetidos a sham (controle) ou sepse por ligação e perfuração cecal (CLP). 24 horas e 10 dias após a sepse os animais foram eutanasiados e estruturas foram removidas: adrenal, rim, pulmão, soro e coração para a determinação dos níveis de proteínas carboniladas e adrenal para verificação do peso dessa estrutura. Resultados: A sepse aumentou o dano oxidativo em diferentes órgãos sistêmicos, incluindo o soro. Não houve um aumento significativo de proteínas carbonilas no coração e nos rins. Fenótipo ansioso potencializa esse dano. Conclusão: Esses achados sugerem que um fenótipo ansioso associado a sepse pode induzir dano mais pronunciado aos órgãos e promover mais alterações no eixo HPA. Esses achados podem ajudar a explicar, pelo menos em parte, o ponto comum dos mecanismos envolvidos na fisiopatologia da sepse e da ansiedade.