Gut microbial clues to bipolar disorder: State‐of‐the‐art review of current findings and future directions

Abstract

Trillions of microorganisms inhabiting in the human gut play an essential role in maintaining physical and mental health. The connections between gut microbiome and neuropsychiatric diseases have been recently identified. The pathogenesis of bipolar disorder, a spectrum of diseases manifesting with mood and energy fluctuations, also seems to be involved in the bidirectional modulation of the microbiome‐gut‐brain (MGB) axis. In this review, we briefly introduce the concept of MGB axis, and then focus on the previous findings in human studies associated with bipolar disorder. These studies provided preliminary evidences on the gut microbial alterations in bipolar disorder. Limitations in these studies and future directions in this research field, such as fecal microbiome transplantation and microbiome‐targeted therapy, were discussed. A research framework linking gut microbiome to determinants and health‐related outcomes in BD was also proposed. Better characterizing and understanding of gut microbial biosignatures in bipolar patients contribute to clarify the etiology of this intractable disease and pave the new way for treatment innovation.

New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data

“…In previous studies, we also found abnormal expression of immune checkpoint inhibitors on peripheral CD8+T cells, such as T cell immunoglobulin and mucin domain 3 (TIM-3), indicating potential disturbances in cellular immunity in BD individuals (19,20). Moreover, the neuroinflammatory modifications may interact with or be affected by the unbalanced kynurenine pathways and reduction in the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) (16,21). Kynurenine aminotransferase-2 (KAT-2) is the key role enzyme regulating the production of neuroprotective kynurenic acid (KYNA) from kynurenine (KYN) in the tryptophan metabolism (22).…”

Obesity and the Brain

“…Fecal microbiome analysis of BD subjects shows a reduced abundance of Bacteroides and Firmicutes , particularly Faecalibacterium , and overall reduced diversity of gut microbiota [ 260 ]. Preliminary results from clinical trials indicate that microbiome-targeted therapies might be useful in the treatment or even prevention of BD [ 261 ].…”

Impaired blood‐brain barrier in the microbiota‐gut‐brain axis: Potential role of bipolar susceptibility gene TRANK1

“…Moreover, we reported gut microbiol signatures can effectively distinguish unipolar and bipolar patients during depressive episodes 28 . In addition, we have systematically reviewed the research advances on gut microbiota in mood disorders and have proposed future research directions in this field 27,29,30 . Given the limited number of studies, small to moderate sample sizes, different ethnicity and regions, uncontrolled clinical characteristics and medications across studies, findings in these studies have both similarities and differences, and thus should be interpreted carefully.…”