Schizophrenia and aggressive behavior: what involvement of the intestinal microbiota?

Schizophrenia affects 1% of the adult population, especially young adults. This psychiatric disease is thought to increase the propensity for aggressiveness, although we do not really know why. Nevertheless, some leads are emerging, involving the intestinal microbiota and a possible bacterial translocation in case of loss of watertightness of the intestinal mucosa. Following this hypothesis, a recent study profiled the diversity and composition of the intestinal microbiota, certain fecal SCFAs (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) (short chain fatty acids) and neurotransmitters of 50 schizophrenic patients, 25 of whom had aggressive behaviors. Objective: to understand the link between inflammation, oxidation, intestinal permeability and microbiota in schizophrenic patients with aggressive behavior.

An inflammatory phenotype...

The results show that schizophrenic patients with aggressive tendencies had significantly increased levels of serum biomarkers of nucleic acid and lipid oxidation compared to non-aggressive schizophrenic patients. These pro-oxidative and pro-inflammatory responses were related to the severity of aggression, suggesting a co-implication of systemic inflammation and oxidation in the development of aggression in schizophrenia.

... coupled with bacterial dysbiosis

Schizophrenic patients with aggressive tendencies also showed a much lower bacterial diversity. This intestinal dysbiosis thus seems to be correlated with the etiology or the severity of aggressiveness in schizophrenic individuals, although it cannot be concluded that there is a causal relationship.

Furthermore, the abundance of the genus Prevotella was significantly increased, while Bacteroides, Faecalibacterium, Blautia, Bifidobacterium, Collinsella and Eubacterium coprostanoligenes were greatly depleted in the group of patients with aggressive tendencies. This change was accompanied by significant reductions in some metabolites, although the authors could not establish a causal relationship: 6 fecal SCFAs (acetic, propanoic, butyric, isobutyric, isovaleric, and isohexanoic acids) and 6 neurotransmitters (5-hydroxytryptophan, levodopa, norepinephrine hydrochloride, adrenaline hydrochloride, kynurenic acid, and histidine) were found to be significantly less present in patients with aggressive behavior.

A hypothesis to be confirmed

Considering these results as a whole, the authors hypothesize that the systemic pro-inflammatory phenotype previously observed in schizophrenics with aggressive tendencies would involve alterations of the intestinal microbiota and its metabolites, hyper-permeability of the intestinal wall allowing intestinal bacteria to reach the general circulation by causing oxidative stress, linked to the severity of the aggressive character. Thus, hyper-inflammation would have led, via the intestinal microbiota, to hyper-oxidation and ultimately to aggressiveness. This hypothesis has yet to be validated in larger-scale studies.