Antibiotic-induced dysbiosis does not potentiate the effect of lipopolysaccharide insult in male Wistar rats

The present study investigated whether neonatal exposure to the proinflammatory endotoxin lipopolysaccharide (LPS) followed by antibiotic (ATB)-induced dysbiosis in early adulthood could induce schizophrenia-like behavioral changes in adult male rats. The combination of these two stressors resulted in decreased weight gain, but no significant behavioral abnormalities were observed. LPS treatment resulted in adult rats hypoactivity and induced anxiety-like behavior in the social recognition paradigm, but these behavioral changes were not exacerbated by ATB-induced gut dysbiosis. ATB treatment seriously disrupted the gut bacterial community, but dysbiosis did not affect locomotor activity, social recognition, and acoustic reactivity in adult rats. Fecal bacterial community analyzes showed no differences between the LPS challenge exposed/unexposed rats, while the effect of ATB administration was decisive regardless of prior LPS exposure. ATB treatment resulted in significantly decreased bacterial diversity, suppression of Clostridiales and Bacteroidales, and increases in Lactobacillales, Enterobacteriales, and Burkholderiales. The persistent effect of LPS on some aspects of behavior suggests a long-term effect of early toxin exposure that was not observed in ATB-treated animals. However, an anti-inflammatory protective effect of ATB cannot be assumed because of the increased abundance of pro-inflammatory, potentially pathogenic bacteria ( Proteus, Suttrella ) and the elimination of the bacterial families Ruminococcaceae and Lachnospiraceae , which are generally considered beneficial for gut health. ### Competing Interest Statement TP declare to have shares in Psyon s.r.o., has founded PSYRES - Psychedelic Research Foundation and has shares in Společnost pro podporu neurovedniho vyzkumu s.r.o. TP reports consulting fees from GH Research and CB21-Pharma outside the submitted work. TP is involved in Compass Pathways trials with psilocybin and MAPS clinical trial with MDMA outside the submitted work.