Age and sex-dependent gut alterations in mice induced by neonatal immune activation with lipopolysaccharide.

Neonatal immune activation (NIA) through exposure to lipopolysaccharide (LPS) induces adult behavioral changes in rodents that resemble symptoms of developmental disorders, such as autism spectrum disorder. The neonatal timing of LPS exposure appears to play a crucial role in determining the nature and extent of long-term changes. This study aims to explore whether a 3-day LPS-NIA triggers sex- and age-related changes in gut function, potentially linking LPS-NIA to gastrointestinal dysfunction. Male and female Swiss mice received intraperitoneal injections of LPS or saline on postnatal days (PN) 3, 5, and 7. At PN35 (juvenile) and PN70 (adult), gut inflammation and oxidative stress were evaluated in addition to assessments of working memory, depressive-like symptoms, sociability, and repetitive behavior. Gut examination showed elevated C-X-C motif chemokine receptor 3 (CXCR3) in LPS-NIA mice, while MyD88 and Zonulin expressions were significantly higher only in adult LPS-NIA females. Interleukin (IL)-23 expression increased in juvenile and adult male and juvenile female LPS-NIA mice. Oxidative changes included decreased duodenal reduced glutathione (GSH) in juvenile females and ileal GSH in adult females exposed to LPS-NIA. Regarding behavioral alterations, adult LPS-NIA females exhibited depressive-like behavior. Working memory deficits were observed across all LPS-NIA groups. Only juvenile LPS-NIA females increased grooming, while rearing was higher in adult LPS-NIA mice of both sexes. The findings imply that LPS-NIA impacts intestinal barrier function and causes gut inflammatory alterations that are sex- and age-specific. These findings pave the way for exploring potential mechanisms that could contribute to LPS-induced gastrointestinal disturbances among individuals with ASD.

A relação do transtorno do espectro autista e a disbiose intestinal: uma revisão integrativa / The relationship between autism spectrum disorder and intestinal dysbiosis: an integrative review

Objetivos: evidenciar as relações e a existência do agravamento do Transtorno do Espectro Autista devido à disbiose intestinal. Métodos: revisão integrativa realizada segundo a pergunta norteadora: Existe comprovação científica entre a relação do TEA e disbiose intestinal que favoreça a melhora na prática clínica e indicações de possíveis respostas? Buscou-se por artigos publicados entre janeiro de 2016 e janeiro de 2021, nas bases de dados: PubMed, SciELO, LILACS, GOOGLE ACADÊMICO. Foram utilizados os descritores (DeCS): "Transtorno do Espectro Autista"; "Microbiota gastrointestinal"; "Disbiose", associados pelo operador booleano "E". Foram incluidos artigos de revisões bibliográficas, completos, originais, limitados aos idiomas inglês e português brasileiro, publicados nos últimos cinco anos, e que, após leitura do resumo, estivessem dentro do escopo da revisão. Resultados: Foram identificados 52 manuscritos e, após aplicação dos critérios de inclusão e exclusão, foram considerados 11 artigos que evidenciam o agravamento do TEA por fatores intrínsecos à microbiota intestinal. Conclusão: existe importante influência causal do eixo bidirecional cérebro-intestino-microbiota na etiologia e exacerbaçao das manifestações clínicas do Transtorno do Espectro Autista devido à disbiose intestinal e aos fatores gastrointestinais de origem idiopática.

Objectives: to highlight the relationships and the existence of Autistic Spectrum Disorder aggravation due to intestinal dysbiosis. Methods: integrative review conducted according to the guiding question: Is there scientific evidence of the relationship between ASD and intestinal dysbiosis that favors improvement in clinical practice and indications of possible answers? We searched for articles published between January 2016 and January 2021 in databases: PubMed, SciELO, LILACS, and GOOGLE ACADEMIC. The following descriptors (DeCS) were used: "Autistic Spectrum Disorder"; "Gastrointestinal microbiota"; "Dysbiosis", associated with the Boolean operator "AND". We included literature review articles, complete, original, limited to English and Brazilian Portuguese languages, published in the last five years, and which, after reading the abstract, were within the scope of the review. Results: 52 manuscripts were identified, and after applying the inclusion and exclusion criteria, 11 articles were considered that show the worsening of ASD due to factors intrinsic to the intestinal microbiota. Conclusion: there is an important causal influence of the bidirectional brain-gut-microbiota axis in the etiology and exacerbation of clinical manifestations of Autism Spectrum Disorder due to intestinal dysbiosis and gastrointestinal factors of idiopathic origin.