Authors
Xin Zhang, Wei-Jian Han, Chen Sun, Lei Yi
Published in
Journal of affective disorders. Pages 122389. Aug 16, 2026. Epub Aug 16, 2026.
Abstract
To investigate early metabolic changes, gut microbiota alterations, and the correlations between key bacterial genera and metabolic indices in patients with bipolar disorder experiencing manic episodes who were treated with different antipsychotics combined with lithium carbonate.
This prospective observational follow-up study enrolled inpatients with bipolar disorder experiencing manic episodes who were medication-free at baseline. Participants were assigned according to treatment regimen into four groups: olanzapine combined with lithium carbonate, risperidone combined with lithium carbonate, aripiprazole combined with lithium carbonate, and lithium carbonate monotherapy. Metabolic parameters, including body weight, body mass index, waist circumference, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol, were measured at baseline (T0), week 4 (T4), week 8 (T8), and week 12 (T12). Fecal samples were collected at T0 and T12, and gut microbiota composition was analyzed using 16S rRNA gene sequencing. Longitudinal changes in metabolic indices, α- and β-diversity of the gut microbiota, and genus-level differences in bacterial abundance were compared among groups. Spearman's rank correlation analysis was used to assess associations between changes in key bacterial genera and changes in metabolic parameters.
A total of 80 patients were enrolled, and 68 completed the 12-week follow-up, with an overall dropout rate of 15.0%. From T0 to T12, changes in metabolic parameters differed significantly among the four groups (all P < 0.001). The olanzapine plus lithium carbonate group showed the most pronounced metabolic changes, followed by the risperidone plus lithium carbonate group, whereas changes were less marked in the aripiprazole plus lithium carbonate group and the lithium monotherapy group. α-diversity analysis showed that the Shannon and Simpson indices significantly increased from baseline to week 12 in the olanzapine/risperidone plus lithium carbonate group (both P < 0.05), whereas no significant changes were observed in the other two groups. β-diversity analysis indicated significant shifts in gut microbial community structure after treatment in the olanzapine and risperidone combination groups, while no significant changes were detected in the aripiprazole combination group or the lithium monotherapy group. Spearman correlation analysis showed that the change in centered log-ratio-transformed abundance of Collinsella was negatively correlated with changes in HDLC, whereas the change in Bifidobacterium abundance was positively correlated with changes in HDLC. The change in Blautia abundance was positively correlated with changes in triglycerides, while the change in Faecalibacterium abundance was negatively correlated with changes in BMI.
Different antipsychotics combined with lithium carbonate were associated with distinct early metabolic burdens and gut microbiota alterations in patients with bipolar disorder experiencing manic episodes. Changes in gut microbiota composition were correlated with changes in metabolic indices, suggesting that the gut microbiota may be involved in the development of early antipsychotic-associated metabolic abnormalities.
PMID:
42604694
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.
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