Antibiotic-induced microbiota depletion in normally-reared adult rats mimics the neuroendocrine effects of early life stress

• Published in: Brain research Vol. 1793; p. 148055
• Main Authors: Ruiz-González, Roberto, Lajud, Naima, Tejeda-Martínez, Aldo Rafael, Flores-Soto, Mario Eduardo, Valdez-Alarcón, Juan José, Tellez, Luis A., Roque, Angélica
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2022
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Behavior, Animal - physiology; Corticosterone; Doublecortin; Dysbiosis; Glucose - metabolism; HPA axis; Hypothalamo-Hypophyseal System - metabolism; Iba1; Maternal Deprivation; Maternal separation; Microbiota; Pituitary-Adrenal System - metabolism; Rats; Stress, Psychological; MS180; AIMD; Corticosterone; FST; PND; HPA axis; Iba1; CONT; ELS; CORT; Maternal separation; Doublecortin; HPA; qPCR; GC
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2022.148055

[Display omitted] •AIMD produced effects similar to MS180 on neurogenesis, behavior, and CORT levels.•AIMD caused a mild attenuation of the MS180-induced metabolic imbalance.•Hippocampal plasticity correlated with CORT levels, behavioral and metabolic outcomes.•Lactobacillus spp, Bacteroides fragilis, Clostridium coccoides, and Clostridium leptum correlated with behavior.•Lactobacillus spp, Bacteroides fragilis, and Clostridium coccoides, positively correlated with neurogenesis. Early life stress induced by maternal separation (MS) causes neuroendocrine, behavioral, and metabolic alterations that are related to gut dysbiosis. MS also increases microglial activation and decreases neurogenesis. Whether these long-term alterations are maintained or worsened in the absence of gut microbiota remains unknown. Hence, this study evaluated the effect of MS symptomatology after antibiotic-induced microbiota depletion (AIMD) in adult rats. Control and maternally separated (3 h per day from postnatal day one to 14, MS180) rats were subjected to AIMD for one month, then assessed for behavioral, metabolic, and neuroendocrine responses. Effects of MS180 and AIMD on gut microbiota were confirmed by qPCR. The data indicate that MS180 caused a passive coping strategy in the forced swimming test and decreased hippocampal neurogenesis. In addition, fasting glucose, cholesterol, and corticosterone levels increased, which correlated with a decrease in Lactobacillus spp counts in the caecum. AIMD also increased immobility in the forced swimming test, decreased hippocampal neurogenesis, and augmented corticosterone levels. However, it had no effects on glucose homeostasis or plasma lipid levels. Furthermore, the MS180-induced long-term effects on behavior and neurogenesis were not affected by microbiota depletion. Meanwhile, the metabolic imbalance was partially reversed in MS180 + AIMD rats. These results show that AIMD mimics the behavioral consequences of MS180 but may prevent metabolic imbalance, suggesting that gut dysbiosis could be part of the mechanisms involved in the maintenance of the long-term consequences of early life stress.