The gut microbiota is a complex community comprising around 10^14 bacteria that live in the gut lumen. The imbalance of the normal structure and function of the microbiota, defined as dysbiosis, has been related to a wide diversity of pathologies, including mental health disorders. However, clinical evidence of the relationship between microbiota and mood disorders is lacking. The aim of this project is to examine the possible relationship of gut dysbiosis and the diagnosis of bipolar disorder (BD), of gut dysbiosis and mood relapses and of gut dysbiosis and cognitive impairment in bipolar patients.

A prospective longitudinal study will be carried out with three groups of patients: a group of euthymic bipolar I or II patients without cognitive impairment (n=50), a second group of euthymic bipolar I or II patients with cognitive impairment (n=50) and a control group of healthy volunteers (n=50). Cognitive impairment will be defined as performance in any test of a domain below 2 standard deviations or more from the mean of normative data of each test assessed in the control group. Subjects will be recruited in the Hospital Clinic of Barcelona. At baseline clinical variables and diet patterns (ROME III) will be collected and neuropsychological performance (WCST, FAS, Stroop Colour-Word Interference test, TMT, WAIS-III, CVLT-II) and functionality (FAST) will be assessed. All subjects will be reassessed at 12 months follow-up. The mood state and possible affective relapses will be evaluated and treatments will be registered. All patients will receive standard psychiatric care according to international guidelines on bipolar disorders. Fecal samples will be collected and then frozen in the morning pre-prandial after having fasted overnight. DNA will be separated and stored at -80°C until assayed. Sequencing will be performed on an Illumina MiSeqTM platform. Statistical analysis will be performed with the latest existing version of the SPSS.

Inclusion Criteria:

• Patients:

  • Diagnosis of bipolar disorder type I or II according to DSM-IV criteria (SCID);
  • Age between 18-55 years;
  • Euthymia (YMRS<6 and HMDRS<8) for at least 3 months;
  • Signed informed consent.

• Healthy controls:

  • No psychiatric diagnosis (SCID);
  • Age between 18-55 years; euthymia (YMRS<6 and HMDRS<8);
  • Signed informed consent.

Exclusion Criteria:

• Use of any type of antibiotics, antifungals or pro/prebiotics within at least one month prior to recruitment;
• IQ<85;
• Neurological illness;
• Stomach/gut problems;
• Current diagnosis of substance abuse or dependence according to DSM-IV criteria (SCID);
• Electroconvulsive therapy in the last year.

Subjects with BD will be recruited in the Bipolar Unit outpatient clinic in the Hospital Clinic of Barcelona. Healthy volunteers will be selected from the community.