Antipsychotic-induced gastrointestinal hypomotility and the alteration in gut microbiota in patients with schizophrenia

Gut microbiota play an important role in the pathogenesis of gut hypomotility and are critical for the production of the intestinal immune system and the maintenance of the intestinal homeostasis. Patients with psychotic disorders are at a high risk of antipsychotic-induced constipation. However, the mechanisms might be more than neurotransmission properties of antipsychotics.We recruited a total of 45 patients with constipation according to Rome IV criteria and objective test for colonic motility and the other 45 gender- and age-matching patients without constipation and investigated their differences in composition of gut microbiota. The demographic and serum metabolic indices were collected. The subjective constipation assessment scale (CAS) and the Bristol stool classification (BSS) were also used to evaluate the degree of constipation in both groups. The fecal samples were analysed using the 16S rRNA gene sequencing.The constipation group had a significantly increased alpha diversity in Observed species, Chao 1, and ACE as compared to the non-constipation group. At the phylum levels, the relative abundances of Bacteroidetes and Fusobacteria decreased significantly, while those of Firmicutes, Verrucomicrobia, and Synergistetes increased significantly in the constipation group. At the genus level, the relative abundances of Christensenella and Desulfovibrio were higher in the constipation group. The α-diversity indices of gut microbiota were correlated positively with the levels of serum total bile acid and correlated negatively with BSS scores. The BSS scores were positively correlated with the relative abundance of Bacteroidetes but negatively correlated with the relative abundance of Firmicutes. PICRUSt analysis revealed the potential metabolic pathways of lipopolysaccharide, vitamin B6, riboflavin, pyruvate, and propionate functions.The alternation of the gut microbiota in schizophrenia patients with antipsychotic-induced constipation indicates antipsychotic agents might affect gastrointestinal motility via varying microbiome-related metabolites, and the specific bacteria, such as Synergistetes which might act as an anti-inflammatory factor in the healthy human gut, related to colonic transit motility seem inconsistent to the findings from previous literature in gastroenterology. However, the causal effects are still unknown. Our study provides a new possibility to understand the mechanisms of antipsychotic-induced constipation.