The purpose of this study is to determine if taking a synbiotic supplement versus a placebo will reduce symptoms of schizophrenia when used in addition to standard antipsychotic medications.

A total of n=68 participants with schizophrenia or schizoaffective disorder who have residual psychotic symptoms which are of at least moderate severity will be randomized. Intestinal inflammation will be assessed through the measurement of antibodies to Saccharomyces cerevisiae, gliadin, Candida albicans as well as high-sensitivity C-Reactive protein and Pentraxin-3. The duration of the trial is 14 weeks: after a 2-week placebo run in, the participants will be randomized to receive the synbiotic compound or identical-appearing placebo over the 12 weeks of the randomized phase. The synbiotic compound is a quality-tested product, Probio-Tec ABCG-Stick-25, manufactured by ChrHansen which contains 4 strains of probiotic microorganisms - Bifidobacteria BB-12, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus rhamnosus - and the prebiotic, inulin, a fructan-containing polysaccharide which has been shown to increase the level of non-pathogenic bacteria in the gastrointestinal tract. All participants will also be maintained on a stable regimen of psychiatric medications prescribed by their treating psychiatrist.

Inclusion Criteria:

• Age 18-65, inclusive.
• Capacity for written informed consent.
• Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder (APA 2013) as determined by the Structured Clinical Interview for DSM-5 Disorders (SCID-5).
• Outpatient at the time of enrollment.
• Residual psychotic symptoms of at least moderate severity as evidenced by a Positive and Negative Syndrome Scale (Kay et al., 1987) (PANSS) total score of 60 or higher AND one or more of the following: one or more PANSS positive symptom scores of 4 or higher; OR containing at least three positive or negative items with scores of 3 or higher at the screening visit.
• Receiving antipsychotic medication for at least 8 weeks prior to starting the study with no medication changes within the previous 21 days.
• Proficient in the English language.

Exclusion Criteria:

• DSM-5 diagnosis of intellectual disability or comparable diagnosis determined by previous versions of the DSM.
• Any clinically significant or unstable medical disorder as determined by the investigators, including congestive heart failure, liver disease, renal failure, any diagnosis of cancer undergoing active treatment.
• A primary immunodeficiency condition such as HIV infection, or undergoing cancer chemotherapy, or receiving systemic corticosteroids, methotrexate or monoclonal antibodies for treatment of an autoimmune disorder.
• History of IV drug use.
• DSM-5 diagnosis of a moderate or severe substance use disorder, except for caffeine or tobacco, within the last three months prior to the screening visit. If the patient has a positive drug toxicity screen at the time of visit 1 (screening) further evaluation by the investigator will be done of the substance use to determine eligibility.
• Participated in any investigational drug trial in the past 30 days.
• Pregnant or planning to become pregnant during the study period.
• Receipt of antibiotic medication within the 14 days prior to visit 2 (as anaerobic organisms residing in the gastrointestinal tract may be minimally affected by antibiotics). Of note, patients on antibiotic may be re-screened once the minimum duration of time since antibiotics use has been met.
• Current and regular use of a probiotic and or prebiotic supplement within the past 2 weeks. Of note, patients taking prebiotic or probiotic supplements may be re-screened.
• Documented inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) or celiac disease

Demographic, symptom, and cognitive data will be shared with the National Database for Clinical Trials Related to Mental Illness (NDCT). Access may be obtained through an approved application with the NDCT.