Microalgae-based bacteria for oral treatment of ASD through enhanced intestinal colonization and homeostasis

Rationale: Exogenous supplementation of beneficial intestinal bacteria can alleviate the behavioural symptoms of psychiatric disorders, such as autism spectrum disorder (ASD), through gut-brain interactions. However, the application of beneficial bacteria, such as Lactobacillus reuteri (L. reuteri), for treating ASD is hindered by limited gut colonization. Methods: Utilizing Spirulina platensis (SP) as a natural microcarrier for intestinal bacteria, a safer and more natural binding approach was employed to bind intestinal bacteria to the surface of SP to produce SP-intestinal bacteria. Due to the high adhesion efficiency and long residence time of SP in the intestines, SP-intestinal bacteria exhibit stronger intestinal colonization ability and better therapeutic effects on ASD. Results: SP is an effective carrier that can bind and deliver bacteria of different shapes and with different gram-staining properties. SP-intestinal bacteria exhibited enhanced colonization capabilities both ex vivo and in vivo. Further research showed that SP-L. reuteri had greater intestinal colonization efficiency than L. reuteri. SP-L. reuteri showed a stronger therapeutic effect on alleviating social deficits in an ASD mouse model by modulating the gut microbiota, enhancing intestinal barrier integrity, reducing lipopolysaccharide entry into the blood and mediating the neuroinflammatory response in the paraventricular thalamic nucleus. Conclusions: This study reports a microalgae-assisted intestinal bacterial delivery system for enhancing intestinal bacterial transplantation for gut-brain axis- or other intestinal-related diseases.