Antibiotic-induced gut dysbiosis and cognitive, emotional, and behavioral changes in rodents: a systematic review and meta-analysis

Abstract

There are previous epidemiological studies reporting associations between antibiotic use and psychiatric symptoms. Antibiotic-induced gut dysbiosis and alteration of microbiota-gut-brain axis communication has been proposed to play a role in this association. In this systematic review and meta-analysis, we reviewed published articles that have presented results on changes in cognition, emotion, and behavior in rodents (rats and mice) after antibiotic-induced gut dysbiosis. We searched three databases—PubMed, Web of Science, and SCOPUS to identify such articles using dedicated search strings and extracted data from 48 articles. Increase in anxiety and depression-like behavior was reported in 32.7 and 40.7 percent of the study-populations, respectively. Decrease in sociability, social novelty preference, recognition memory and spatial cognition was found in 18.1, 35.3, 26.1, and 62.5 percent of the study-populations, respectively. Only one bacterial taxon (increase in gut Proteobacteria) showed statistically significant association with behavioral changes (increase in anxiety). There were no consistent findings with statistical significance for the potential biomarkers [Brain-derived neurotrophic factor (BDNF) expression in the hippocampus, serum corticosterone and circulating IL-6 and IL-1β levels]. Results of the meta-analysis revealed a significant association between symptoms of negative valence system (including anxiety and depression) and cognitive system (decreased spatial cognition) with antibiotic intake (p < 0.05). However, between-study heterogeneity and publication bias were statistically significant (p < 0.05). Risk of bias was evaluated to be high in the majority of the studies. We identified and discussed several reasons that could contribute to the heterogeneity between the results of the studies examined. The results of the meta-analysis provide promising evidence that there is indeed an association between antibiotic-induced gut dysbiosis and psychopathologies. However, inconsistencies in the implemented methodologies make generalizing these results difficult. Gut microbiota depletion using antibiotics may be a useful strategy to evaluate if and how gut microbes influence cognition, emotion, and behavior, but the heterogeneity in methodologies used precludes any definitive interpretations for a translational impact on clinical practice.

Exploring the Influence of Gut–Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics

“…This summary underscores the critical importance and urgency of using probiotics and advancing research related to cognitive aging. Ongoing studies aim to deepen our understanding of the interactions within the microbiome–gut–brain axis, particularly exploring mechanisms between the gastrointestinal tract and the nervous system [ 122 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 ]. Future research should focus on more precise analyses and explorations of the composition of gut microbiota, identifying which strains are dominantly associated with conditions such as anxiety, depression, Parkinson’s disease, and other psychiatric and cognitive disorders, including Alzheimer’s disease [ 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 ].…”

Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model

“…These changes in social behavior are unique to this marmoset model because we tested these changes in well-established pair-mates of opposing genders (a characteristic unique to marmosets), whereas the social behavior tested in rodents focus on social preference (preferring another rodent over an object) and social novelty (preferring a novel rodent over a known rodent). 11 , 51 Moreover, these experiments are usually performed with only male rodents, which tend to exhibit either an aggressive, fight-or-flight response or avoidance response as compared to the more affiliative, tend-and-befriend response shown by females. 28 , 52 The existing literature on rodent models suggest either a decrease in sociability or no change in social behavior post-antibiotic-induced dysbiosis, 11 whereas our study uniquely presents a case for an increase in sociability after oral antibiotic intervention, albeit as a consequence of potential stress.…”

“… 11 , 51 Moreover, these experiments are usually performed with only male rodents, which tend to exhibit either an aggressive, fight-or-flight response or avoidance response as compared to the more affiliative, tend-and-befriend response shown by females. 28 , 52 The existing literature on rodent models suggest either a decrease in sociability or no change in social behavior post-antibiotic-induced dysbiosis, 11 whereas our study uniquely presents a case for an increase in sociability after oral antibiotic intervention, albeit as a consequence of potential stress. There were potential changes in piloerection and genital display in control group, but the results of these behaviors were not statistically robust and prone to outlier influence.…”

“… 8 Several gut microbes have been correlated with fluctuations in levels of corticosteroids in both human 8–10 and rodent studies. 11 Certain probiotic bacteria, such as Lactobacillus spp. and Bifidobacterium spp., have been shown to decrease corticosteroid production in healthy humans 12 and in mice exposed to stressful stimuli.…”

“… 19 Several studies in rodents have linked antibiotic-induced gut dysbiosis to the development of depressive symptomatology. 11 , 18 In these studies, administration of antibiotics such as penicillins, sulfonamides, glycopeptides (specifically, vancomycin) and quinolones was shown to lead to the development of signs consistent with depression such as spending less time in open arms of elevated plus mazes, increased immobility time on forced swim and tail suspension tests, impaired object recognition, and decreased exploratory activity. 11 , 18 …”