A Merchán1, C Pérez-Fernández1, M J López2, J Moreno2, M Moreno1, F Sánchez-Santed1, P Flores3. 1. Department of Psychology and Health Research Center (CEINSA), University of Almería, Ctra. Sacramento s/n, 04120 Almería, Spain. 2. Department of Biology and Geology and CIAMBITAL, University of Almería & CeiA3, Ctra. Sacramento s/n, 04120, Almería, Spain. 3. Department of Psychology and Health Research Center (CEINSA), University of Almería, Ctra. Sacramento s/n, 04120 Almería, Spain. Electronic address: pflores@ual.es.
Abstract
RATIONALE: Compulsive behaviour, present in different psychiatric disorders such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of serotonin (5-hydroxytryptamine, 5-HT). The gut microbiota regulates tryptophan (TRP) metabolism and may affect global 5-H synthesis in the enteric and central nervous systems, suggesting a possible involvement of gut microbiota in compulsive spectrum disorders. OBJECTIVES: The present study investigated whether chronic TRP depletion by diet alters the faecal bacterial community profiles of compulsive versus non-compulsive rats in schedule-induced polydipsia (SIP). Peripheral plasma 5-HT and brain-derived neurotrophic factor (BDNF) levels were evaluated. METHODS: Wistar rats were selected as High Drinkers (HD) or Low Drinkers (LD) according to their SIP behaviour and were fed for 14 days with either a TRP-free diet (T-) or a TRP-supplemented diet (T+). The faecal bacterial community structure was investigated with 16S rRNA gene-targeted denaturing gradient gel electrophoresis (DGGE) fingerprinting analysis. RESULTS: Compulsive HD rats showed a lower bacterial diversity than LD rats, irrespectively of the diet. The TRP-depleted HD rats, the only group increasing compulsive licking in SIP, showed a reduction of bacterial evenness and a highly functionally organized community compared with the other groups, indicating that this bacterial community is more fragile to external changes due to the dominance of a low number of species. The chronic TRP depletion by diet effectively reduced peripheral plasma 5-HT levels in both HD and LD rats, while plasma BDNF levels were not altered. CONCLUSIONS: These results highlight the possible implication of reduced microbial diversity in compulsive behaviour and the involvement of the serotonergic system in modulating the gut brain-axis in compulsive spectrum disorders.
RATIONALE: Compulsive behaviour, present in different psychiatric disorders such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of serotonin (5-hydroxytryptamine, 5-HT). The gut microbiota regulates tryptophan (TRP) metabolism and may affect global 5-H synthesis in the enteric and central nervous systems, suggesting a possible involvement of gut microbiota in compulsive spectrum disorders. OBJECTIVES: The present study investigated whether chronic TRP depletion by diet alters the faecal bacterial community profiles of compulsive versus non-compulsiverats in schedule-induced polydipsia (SIP). Peripheral plasma 5-HT and brain-derived neurotrophic factor (BDNF) levels were evaluated. METHODS:Wistar rats were selected as High Drinkers (HD) or Low Drinkers (LD) according to their SIP behaviour and were fed for 14 days with either a TRP-free diet (T-) or a TRP-supplemented diet (T+). The faecal bacterial community structure was investigated with 16S rRNA gene-targeted denaturing gradient gel electrophoresis (DGGE) fingerprinting analysis. RESULTS:Compulsive HDrats showed a lower bacterial diversity than LD rats, irrespectively of the diet. The TRP-depleted HDrats, the only group increasing compulsive licking in SIP, showed a reduction of bacterial evenness and a highly functionally organized community compared with the other groups, indicating that this bacterial community is more fragile to external changes due to the dominance of a low number of species. The chronic TRP depletion by diet effectively reduced peripheral plasma 5-HT levels in both HD and LD rats, while plasma BDNF levels were not altered. CONCLUSIONS: These results highlight the possible implication of reduced microbial diversity in compulsive behaviour and the involvement of the serotonergic system in modulating the gut brain-axis in compulsive spectrum disorders.
Authors: Ana C Abreu; Santiago Mora; Ana Isabel Tristán; Elena Martín-González; Ángeles Prados-Pardo; Margarita Moreno; Ignacio Fernández Journal: J Proteome Res Date: 2022-02-10 Impact factor: 4.466